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To develop a joint proposal for screening criteria of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and vice versa, which serves as a guidelines in patient referral between the Rheumatology and Pneumology departments to early detection of these patients.A systematic literature review was carried out on the risk factors for the development of ILD in RA patients, and for the referral criteria to Rheumatology for suspected early RA. Based on the available evidence, screening criteria were agreed using the Delphi method by a panel of pneumologists and rheumatologists with expertise in these pathologies.Screening criteria for ILD in patients with RA and for the early detection of RA in cases with ILD of unknown etiology have been developed. In both cases, a detection strategy was based on clinical risk factors. Recommendations also included the complementary tests to be carried out in the different clinical scenarios and on the periodicity that screening should be repeated.A selective screening strategy is recommended for the first time in the early diagnosis of patients with ILD-RA. This multidisciplinary proposal aims to solve some common clinical questions and help decision-making, although its usefulness to identify these patients with good sensitivity must be confirmed in a validation study.

ObjectivesA European League Against Rheumatism taskforce was convened to review the literature and develop recommendations on lifestyle behaviours for rheumatic and musculoskeletal diseases (RMDs).MethodsSix lifestyle exposures (exercise, diet, weight, alcohol, smoking, work participation) and seven RMDs (osteoarthritis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, systemic lupus erythematosus, systemic sclerosis, gout) were considered. The taskforce included health professionals in rheumatology, geriatricians, epidemiologists, public health experts, people with RMDs and exposure domain experts. Systematic reviews were conducted to gather available evidence, from which recommendations were developed.ResultsFive overarching principles and 18 specific recommendations were defined based on available evidence. The overarching principles define the importance of a healthy lifestyle, how lifestyle modifications should be implemented, and their role in relation to medical treatments. Exercise recommendations highlight the safety and benefits of exercise on pain and disability, particularly among people with osteoarthritis and axial spondyloarthritis. The diet recommendations emphasise the importance of a healthy, balanced diet for people with RMDs. People with RMDs and health professionals should work together to achieve and maintain a healthy weight. Small amounts of alcohol are unlikely to negatively affect the outcomes of people with RMDs, although people with rheumatoid arthritis and gout may be at risk of flares after moderate alcohol consumption. Smokers should be supported to quit. Work participation may have benefits on RMD outcomes and should be discussed in consultations.ConclusionsThese recommendations cover a range of lifestyle behaviours and can guide shared decision making between people with RMDs and health professionals when developing and monitoring treatment plans.

Resumen Objetivos La enfermedad pulmonar intersticial difusa (EPID) es una manifestacion frecuente en pacientes con artritis reumatoide (AR) y asocia una gran morbimortalidad. El objetivo de esta revision fue identificar los distintos metodos de cribado de EPID en pacientes con AR. Metodos Se realizo una busqueda sistematica en Pubmed, Embase y Cochrane Library hasta abril de 2020 y una busqueda manual en la bibliografia de los articulos recuperados. Se limito a estudios en humanos y articulos publicados en ingles, frances o espanol. Se seleccionaron estudios de cualquier diseno en los que: a) la poblacion a estudiar fuesen pacientes adultos con AR; b) la intervencion consistiese en cualquier metodo de cribado de EPID; y c) se evaluase la validez o fiabilidad del metodo de cribado, o se describiesen criterios de cribado. Dos revisoras realizaron la seleccion por titulo y abstract de forma independiente y posteriormente extrajeron la informacion utilizando plantillas especificas. Resultados Se incluyeron 25 estudios con un total de 2.593 pacientes. La herramienta mas frecuentemente utilizada para el cribado de EPID fue la tomografia computarizada de alta resolucion (TCAR) pulmonar. Tambien se evaluaron la auscultacion electronica, los marcadores bioquimicos, el lavado broncoalveolar (LBA), las pruebas de funcion respiratoria (PFR) y la ecografia pulmonar. En los diferentes estudios, la auscultacion electronica y la ecografia pulmonar alcanzaron mayor precision que las PFR, el LBA y los marcadores bioquimicos. Conclusiones La TCAR ha demostrado ser la tecnica mas sensible para el cribado de EPID en pacientes con AR. Dada su inocuidad y su alta sensibilidad, es posible que la ecografia pulmonar se posicione como tecnica de eleccion en un futuro.

Resumen Objetivo Elaborar recomendaciones para la prevencion de infeccion en pacientes adultos con enfermedades reumaticas autoinmunes sistemicas (ERAS). Metodos Un panel de expertos, seleccionados con base en su curriculum y experiencia, identifico preguntas clinicas de investigacion relevantes para el objetivo del documento. Se realizaron revisiones sistematicas de la evidencia, que se graduo de acuerdo con los criterios del Scottish Intercollegiate Guidelines Network. Tras ello, se formularon las recomendaciones. Resultados Se seleccionaron cinco preguntas, referentes a la prevencion de infeccion por Pneumocystis jirovecii con trimetoprim-sulfametoxazol, medidas profilacticas contra el virus de la hepatitis B, vacunacion contra el virus del papiloma humano, vacunacion contra el Streptococcus pneumoniae y vacunacion contra el virus de la gripe. Se formularon un total de 18 recomendaciones, estructuradas por pregunta, con base en la evidencia encontrada para las diferentes ERAS y/o consenso de expertos. Conclusiones Existe suficiente evidencia sobre la seguridad y eficacia de las vacunaciones y otras medidas profilacticas frente a los microrganismos revisados en este documento como para ser recomendadas especificamente en pacientes con ERAS.

OBJECTIVE: A EULAR taskforce was convened to develop recommendations for lifestyle behaviours amongst people with rheumatic and musculoskeletal diseases (RMDs). This paper reviews the literature on work-related factors and disease-specific outcomes for people with osteoarthritis, rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis (axSpA), psoriatic arthritis, systemic sclerosis (SSc) and gout.METHODS: Two separate systematic literature reviews (SLRs) were conducted. The first identified SLRs, published between 01/2013 and 09/2018. The second identified original observational and intervention studies published before 05/2019. Manuscripts were included if they assessed the effects of vocational interventions on disease-specific outcomes (i.e. clinical outcomes, patient-reported outcomes, and work outcomes) or if they assessed the association between work-related factors and these outcomes. Medline, Embase, Cochrane Library of systematic reviews and CENTRAL databases were searched.RESULTS: Two SLRs were identified including individuals with SSc and inflammatory arthritis. Subsequently, 23 original manuscripts were identified, with most of them (43.5%) including people with RA and no manuscripts on gout. Most observational studies evaluated the association between work-related factors and work outcomes while limited information was available on the impact of work on clinical outcomes. A few studies suggested that physically demanding jobs have a small detrimental effect on radiographic progression in axSpA and PsA. Intervention studies showed beneficial effects of vocational interventions for disease-specific outcomes, but with small effect sizes.CONCLUSION: Many studies indicated that work participation is not likely to be detrimental and, in some cases, may be beneficial for RMD-specific outcomes and should therefore receive attention within healthcare consultations.

Osteoarthritis (OA) is closely linked to the increase in the number of senescent cells in joint tissues, and the senescence-associated secretory phenotype (SASP) is implicated in cartilage degradation. In the last decade, extracellular vesicles (EV) in combination with the use of miRNAs to modify post-transcriptional expressions of multiple genes have shown their utility in new therapies to treat inflammatory diseases. This work delves into the anti-inflammatory effect of extracellular vesicles derived from mesenchymal stem cells (MSC) previously modified to inhibit the expression of miR-21. We compare the efficacy of two treatments, MSC with their miR-21 inhibited through lentiviral transfection and their EV, against inflammation in a new OA animal model. The modified MSC and their EV were intraperitoneally injected in an OA animal model twice. One month after treatment, we checked which therapy was the most effective to reduce inflammation compared with animals untreated. Treated OA model sera were analyzed for cytokines and chemokines. Subsequently, different organs were analyzed to validate the results obtained. EV were the most effective treatment to reduce chemokines and cytokines in serum of OA animals as well as SASP, in their organs checked by proteomic and genomic techniques, compared with MSC alone in a statistically significant way. In conclusion, MSC-miR-21−-derived EV showed a higher therapeutic potential in comparison with MSCs-miR-21-. They ameliorate the systemic inflammation through inactivation of ERK1/2 pathway in OA in vivo model. Graphical abstract Workflow of the realization of the animal model of OA by injecting cells into the joint cavity of the left knee of the animals, which produces an increase in serum cytokines and chemokines in the animals in addition to the increase in SASP and markers of inflammation. Inhibition of miR-21 in MSCs, from the stroma of the human umbilical cord, by lentivirus and extraction of their EVs by ultracentrifugation. Finally, application of MSC therapy with its miR-21 inhibited or its EVs produces a decrease in serum cytokines and chemokines in the treated animals, in addition to an increase in SASP and markers of inflammation. The cell-free therapy being the one that produces a greater decrease in the parameters studied

BackgroundA EULAR taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). In this paper, the literature on the effect of diet on the progression of RMDs is reviewed.MethodsSystematic reviews and meta-analyses were performed of studies related to diet and disease outcomes in seven RMDs: osteoarthritis (OA), rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis, psoriatic arthritis, systemic sclerosis and gout. In the first phase, existing relevant systematic reviews and meta-analyses, published from 2013 to 2018, were identified. In the second phase, the review was expanded to include published original studies on diet in RMDs, with no restriction on publication date. Systematic reviews or original studies were included if they assessed a dietary exposure in one of the above RMDs, and reported results regarding progression of disease (eg, pain, function, joint damage).ResultsIn total, 24 systematic reviews and 150 original articles were included. Many dietary exposures have been studied (n=83), although the majority of studies addressed people with OA and RA. Most dietary exposures were assessed by relatively few studies. Exposures that have been assessed by multiple, well conducted studies (eg, OA: vitamin D, chondroitin, glucosamine; RA: omega-3) were classified as moderate evidence of small effects on disease progression.ConclusionThe current literature suggests that there is moderate evidence for a small benefit for certain dietary components. High-level evidence of clinically meaningful effect sizes from individual dietary exposures on outcomes in RMDs is missing.

This work was funded by the European League Against Rheumatism. SMMV and JMG are supported by Versus Arthritis (grant number 21755) and the NIHR Manchester Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health., Gwinnutt J.M., Wieczorek M., Cavalli G., Balanescu A., Bischoff-Ferrari H.A., Boonen A., De Souza S., De Thurah A., Dorner T.E., Moe R.H., Putrik P., Rodríguez-Carrio J., Silva-Fernández L., Stamm T., Walker-Bone K., Welling J., Zlatković-Švenda M.I., Guillemin F., Verstappen S.M.M.

To identify recommendations on the diagnosis and management of rheumatoid arthritis (RA) supported by low recommendation grades, to study the causes of this low grading, and to propose solutions. A group of six rheumatologists, with extensive experience in the development of systematic reviews, reviewed national and international RA recommendations and practice guidelines. They identified all recommendations with a low level of evidence or recommendation grade (levels equivalent to 4, 5, or grades C or D of the Oxford Levels of Evidence), classified them by areas (diagnosis, follow-up, treatment, others), and analyzed plausible causes of low graduation. A Delphi was used to select 10 recommendations where it was most important to obtain quality evidence to support them. Subsequently, actions were proposed to improve evidence and recommendation grading. Fourteen documents were analyzed, in which 192 recommendations with low evidence/grade of recommendation were identified, most of which were on treatment. The two most frequent causes of this low level are the absence of studies and the discrepancy between the wording of the recommendation and the evidence used. Finally, the proposed solution to the critical recommendations is a list of unanswered research questions and possible designs to answer them. We propose to design and promote research that truly supports or rectifies clinical practice and, thus, bridges the gap between existing evidence and critical recommendations.

Resumen Objetivos Analizar el riesgo de fractura calculado por FRAX® y la frecuencia de alto riesgo de fractura en la poblacion general en Espana. Metodos EPISER2016 es un estudio transversal multicentrico de base poblacional de la prevalencia de las enfermedades reumaticas en poblacion adulta en Espana. Un total de 3.154 sujetos de edad igual o superior a 40 anos (1.184 hombres y 1.970 mujeres) se seleccionaron mediante muestreo aleatorio estratificado. Las preguntas relacionadas con los factores de riesgo de fractura se realizaron mediante encuesta telefonica. El riesgo de fractura principal (RFP) y de cadera (RFC) se calcularon con la version espanola de la herramienta FRAX®, sin la inclusion de la densidad mineral osea. Para definir alto riesgo de fractura, se utilizaron los umbrales RFP ≥ 20%, RFP ≥ 10%, RFP ≥ 7,5% y RFC ≥ 3%. Resultados La mediana (rango intercuartilico) del RFP fue 2,61% (1,55-6,34%) en mujeres y 1,67% (1,15-2,87%) en hombres; la del RFC fue 0,39% (0,14-1,86%) y 0,18% (0,07-0,77%). El 3,83% de las mujeres y ningun hombre tenian un RFP ≥ 20%; el 15,71% y el 1,14% tenian un RFP ≥ 10%; el 20,62% y el 2,21%, un RFP ≥ 7,5%; y el 19,27% y el 8,05%, un RFC ≥ 3%. En las mujeres de 65 anos o mas, el RFC fue alto en el 58,09%. Conclusiones EPISER2016 nos ha permitido conocer el riesgo de fractura calculado por FRAX® y la prevalencia de alto riesgo de fractura en la poblacion general segun los diversos umbrales utilizados en Espana.

Resumen Objetivo La dificultad para el diagnostico y la variedad de manifestaciones clinicas que pueden determinar la eleccion del tratamiento del sindrome antifosfolipido (SAF) primario ha impulsado a la Sociedad Espanola de Reumatologia (SER) en la elaboracion de recomendaciones basadas en la mejor evidencia posible. Estas recomendaciones pueden servir de referencia para reumatologos y otros profesionales implicados en el manejo de pacientes con SAF. Metodos Se creo un panel formado por 4 reumatologos, una ginecologa y una hematologa, expertos en SAF, previamente seleccionados mediante una convocatoria abierta o por meritos profesionales. Las fases del trabajo fueron: identificacion de las areas claves para la elaboracion del documento, analisis y sintesis de la evidencia cientifica (utilizando los niveles de evidencia de SIGN, Scottish Intercollegiate Guidelines Network) y formulacion de recomendaciones a partir de esta evidencia y de tecnicas de «evaluacion formal» o «juicio razonado». Resultados Se han elaborado 46 recomendaciones que abordan 5 areas principales: diagnostico y evaluacion, medidas de tromboprofilaxis primaria, tratamiento del SAF o tromboprofilaxis secundaria, tratamiento del sindrome antifosfolipido obstetrico y situaciones especiales. Esta incluido tambien el papel de los nuevos anticoagulantes orales, el problema de las recurrencias o los principales factores de riesgo identificados en estos individuos. En este documento se reflejan las ultimas 25, referidas a las areas de: SAF obstetrico y situaciones especiales. El documento contiene una tabla de recomendaciones y algoritmos de tratamiento. Conclusiones Se presentan las recomendaciones de la SER sobre SAF. Este documento corresponde a la parte 2.a relacionada con el SAF obstetrico y las situaciones especiales. Estas recomendaciones se consideran herramientas en la toma de decisiones para los clinicos, teniendo en consideracion tanto la decision del medico experto en SAF como la opinion compartida con el paciente. Se ha elaborado tambien una parte I que aborda aspectos relacionados con el diagnostico, evaluacion y tratamiento.

Objective The difficulty in diagnosis and the spectrum of clinical manifestations that can determine the choice of treatment for primary antiphospholipid syndrome (APS) has fostered the development of recommendations by the Spanish Society of Rheumatology (SER), based on the best possible evidence. These recommendations can serve as a reference for rheumatologists and other specialists involved in the management of APS. Methods A panel of four rheumatologists, a gynaecologist and a haematologist with expertise in APS was created, previously selected by the SER through an open call or based on professional merits. The stages of the work were: identification of the key areas for drafting the document, analysis and synthesis of the scientific evidence (using the Scottish Intercollegiate Guidelines Network [SIGN] levels of evidence) and formulation of recommendations based on this evidence and formal assessment or reasoned judgement techniques (consensus techniques). Results 46 recommendations were drawn up, addressing five main areas: diagnosis and evaluation, measurement of primary thromboprophylaxis, treatment for APS or secondary thromboprophylaxis, treatment for obstetric APS and special situations. These recommendations also include the role of novel oral anticoagulants, the problem of recurrences or the key risk factors identified in these subjects. This document reflects the first 21, referring to the areas of: diagnosis, evaluation and treatment of primary APS. The document provides a table of recommendations and treatment algorithms. Conclusions An update of the SER recommendations on APS is presented. This document corresponds to part I, related to diagnosis, evaluation and treatment. These recommendations are considered tools for decision-making for clinicians, taking into consideration both the decision of the physician experienced in APS and the patient. A part II has also been prepared, which addresses aspects related to obstetric SAF and special situations.

This article belongs to the Special Issue Extracellular Vesicles Research in Inflamm-Aging [Abstract] The accumulation process of proinflammatory components in the body due to aging influences intercellular communication and is known as inflammaging. This biological mechanism relates the development of inflammation to the aging process. Recently, it has been reported that small extracellular vesicles (sEVs) are mediators in the transmission of paracrine senescence involved in inflammatory aging. For this reason, their components, as well as mechanisms of action of sEVs, are relevant to develop a new therapy called senodrugs (senolytics and senomorphic) that regulates the intercellular communication of inflammaging. In this review, we include the most recent and relevant studies on the role of sEVs in the inflammatory aging process and in age-related diseases such as cancer and type 2 diabetes. J.F.L. was funded by Xunta de Galicia, Grant Number ED481D-2021-020. M.C.A. received a grant from the Spanish National Health Institute Carlos III (PI20/00497) Xunta de Galicia; ED481D-2021-020

European League Against Rheumatism [20385, 20380]; NIHR Manchester Biomedical Research Centre, Wieczorek M, Gwinnutt JM, Ransay-Colle M, Balanescu A, Bischoff-Ferrari H, Boonen A, Cavalli G, de Souza S, de Thurah A, Dorner TE, Moe RH, Putrik P, Rodríguez-Carrio J, Silva-Fernández L, Stamm TA, Walker-Bone K, Welling J, Zlatkovic-Svenda M, Verstappen SM, Guillemin F

Resumen Objetivos Describir la metodologia del estudio de prevalencia de las enfermedades reumaticas en la poblacion adulta en Espana, EPISER 2016, asi como sus fortalezas y limitaciones. El objetivo del proyecto es estimar la prevalencia de artritis reumatoide (AR), artropatia psoriasica (APs), espondilitis anquilosante (EA), lupus eritematoso sistemico (LES), sindrome de Sjogren (SS), artrosis (de rodilla, cadera, manos, columna cervical y lumbar), fibromialgia, gota y fractura osteoporotica clinica. Material y metodo Estudio transversal multicentrico de base poblacional en el que participan 45 municipios de las 17 comunidades autonomas. La poblacion de referencia esta compuesta por adultos de 20 o mas anos residentes en Espana. La recogida de informacion se llevara a cabo mediante encuesta telefonica empleando el sistema Computer Assisted Telephone Interview (CATI). Las sospechas diagnosticas y los diagnosticos autorreferidos seran estudiadas por reumatologos del hospital de referencia de los municipios seleccionados. Analisis estadistico: se calcularan las prevalencias de enfermedades reumaticas mediante estimadores y sus IC del 95%. Se calcularan factores de ponderacion en funcion de la probabilidad de seleccion en cada una de las etapas del muestreo. Se tendra en cuenta la distribucion de la poblacion en Espana segun datos del Instituto Nacional de Estadistica. Conclusiones Los cambios sociodemograficos y en habitos de vida durante los ultimos 16 anos justifican la realizacion de EPISER 2016. El estudio ofrecera datos actualizados de prevalencia en AR, EA, APs, LES, SS, artrosis, fibromialgia, gota y fractura osteoporotica clinica. Los resultados permitiran comparar los datos con estudios de otros paises y con el EPISER 2000.

Objectives To develop recommendations for the prevention of infection in adult patients with systemic autoimmune rheumatic diseases (SARD). Methods Clinical research questions relevant to the objective of the document were identified by a panel of experts selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network criteria. Specific recommendations were made. Results Five questions were selected, referring to prevention of infection by Pneumocystis jirovecii with trimethoprim/sulfamethoxazole, primary and secondary prophylactic measures against hepatitis B virus, vaccination against human papillomavirus, vaccination against Streptococcus pneumoniae and vaccination against influenza virus, making a total of 18 recommendations, structured by question, based on the evidence found for the different SARD and/or expert consensus. Conclusions There is enough evidence on the safety and efficacy of vaccinations and other prophylactic measures against the microorganisms reviewed in this document to specifically recommend them for patients with SARD.

Aims Interstitial lung disease (ILD) is frequent in patients with rheumatoid arthritis (RA) and is associated with significant morbidity and mortality. The aim of this review was to identify the different screening methods for ILD in patients with RA. Methods We ran a systematic search in Pubmed, Embase and Cochrane Library up to April 2020 and did a hand search of the references of the retrieved articles. The search was limited to humans and articles published in English, Spanish or French. We selected studies with any design where: (a) the population included adult patients with RA; (b) the intervention was any screening method for ILD; and (c) validity or reliability of the screening method were evaluated, or a screening method was described. Two reviewers independently screened the articles by title and abstract and subsequently extracted the information using a specific data extraction form. Results 25 studies were included with a total of 2593 patients. The most frequently used tool for ILD screening was high resolution computed tomography (HRCT) of the lung. Electronic auscultation, biochemical markers, bronchoalveolar lavage (BAL), pulmonary function tests (PFTs) and lung ultrasonography were also evaluated. Across the different studies, electronic auscultation and lung ultrasonography achieved higher accuracy than PFTs, BAL and biochemical markers. Conclusions HRCT resulted as the most sensitive tool for ILD screening in patients with RA. Given its harmlessness and high sensitivity, lung ultrasonography may become the first-choice tool in the future.

Rheumatoid arthritis (RA) prevalence is believed to be around 1% worldwide, although it varies considerably among different populations. The aim of EPISER2016 study was to estimate the prevalence of RA in the general adult population in Spain. We designed a population-based cross-sectional study. A national survey was conducted between November 2016 and October 2017 involving a probabilistic sample from the general population aged 20 years or older. Subjects were randomly selected for phone screening using a computer-assisted telephone interviewer system. Positive RA screening results were evaluated by a rheumatologist. Cases fulfilled the 1987 ACR and/or the 2010 ACR/EULAR criteria; previous diagnosis established by a rheumatologist and clearly identified in medical records were also accepted regardless of the criteria used. Prevalence estimates with 95% CI were calculated taking into account the design of the sample (weighting based on age, sex, and geographic origin using as a reference the distribution of the population in Spain). 4916 subjects participated in the study and 39 RA cases were confirmed. RA estimated prevalence was 0.82% (95% CI 0.59–1.15). Mean age of RA cases was 60.48 (14.85) years, they were more frequently women (61.5%), from urban areas (74.4%), non-smokers (43.6%), and with a high body mass index (53.8% with overweight). Extrapolating to the population in Spain (approximately 37 million are ≥ 20 years old), it was estimated that there were between 220,000 and 430,000 people aged 20 years or older with RA. No undiagnosed cases were detected, which could be related to the establishment of early arthritis clinics around the country, increasing the rates of diagnosis during early phases of RA.

Objectives Prevalence of SLE varies among studies, being influenced by study design, geographical area and ethnicity. Data about the prevalence of SLE in Spain are scarce. In the EPISER2016 study, promoted by the Spanish Society of Rheumatology, the prevalence estimate of SLE in the general adult population in Spain has been updated and its association with sociodemographic, anthropometric and lifestyle variables has been explored. Methods Population-based multicentre cross-sectional study, with multistage stratified and cluster random sampling. Participants were contacted by telephone to carry out a questionnaire for the screening of SLE. Investigating rheumatologists evaluated positive results (review of medical records and/or telephone interview, with medical visit if needed) to confirm the diagnosis. To calculate the prevalence and its 95% CI, the sample design was taken into account and weighing was calculated considering age, sex and geographic origin. Multivariate logistic regression models were defined to analyse which sociodemographic, anthropometric and lifestyle variables included in the telephone questionnaire were associated with the presence of SLE. Results 4916 subjects aged 20 years or over were included. 16.52% (812/4916) had a positive screening result for SLE. 12 cases of SLE were detected. The estimated prevalence was 0.21% (95% CI: 0.11, 0.40). SLE was more prevalent in the rural municipalities, with an odds ratio (OR) = 4.041 (95% CI: 1.216, 13.424). Conclusion The estimated prevalence of SLE in Spain is higher than that described in most international epidemiological studies, but lower than that observed in ethnic minorities in the United States or the United Kingdom.

Resumen Objetivo Describir la evolucion del grado de atractivo de la Reumatologia en las sucesivas convocatorias MIR de 1983 a 2014. Metodos Se solicito al servicio de Gestion de Formacion Sanitaria Especializada de la Subdireccion General de Ordenacion Profesional del Ministerio de Sanidad espanol datos de eleccion de Reumatologia de las convocatorias MIR de 1983 a 2014: numero de orden de eleccion de la primera y ultima plazas de Reumatologia, asi como la mediana. A efectos de comparacion, se solicito la mediana de eleccion de otras especialidades. Para definir el grado de atractivo de cada especialidad, se realizo un analisis matematico de 1.000 simulaciones sobre la mediana que habria obtenido cada especialidad si se hubieran elegido al azar y se calculo la desviacion entre la mediana observada y la mediana por azar generada mediante las simulaciones. Resultados La mediana de eleccion de Reumatologia presento un rango desde el numero 244 en la convocatoria de 1983 al numero 3.394 en la convocatoria del ano 2008, observandose, en terminos absolutos, un progresivo incremento a lo largo de los anos. La simulacion matematica permitio cuantificar la desviacion entre la mediana observada y la que habria ocurrido si las especialidades se hubieran elegido al azar. Se objetivo una tendencia a la recuperacion del atractivo de Reumatologia en los ultimos anos. Conclusiones Tras un acusado descenso en el atractivo de la Reumatologia entre los electores a plazas MIR durante los ultimos anos del siglo pasado, parece evidenciarse una recuperacion.

Objective To describe the progress of the attractiveness of rheumatology at successive MIR calls, from 1983 to 2014. Methods Candidates in the Spanish training system for medical doctors choose their specialties sequentially, ordered by their ranking in the qualifying exam (MIR). The highest, median and lowest rank of candidates choosing rheumatology training positions in every MIR call from 1983 to 2014 was requested from the Department of Management of Specialized Medical Training (General Department of Professional Regulation; Spanish Ministry of Health). To compare, the same data was requested for other specialties. In order to define and analyze the attractiveness of each specialty we introduce an ‘index of attractiveness’, based on the normalized difference of the actual median rank reported for each year and the average median obtained in 1000 simulations in which candidates choose specialties at random. Results Regarding the median of the election of rheumatology, the range went from 244th in 1983 to 3394th in 2008, showing a progressive increase over the years in absolute figures. A mathematical simulation allowed quantifying the difference between the observed median and what would have happened if specialties had been chosen by pure chance. Results show a tendency to recover the attractiveness of rheumatology in recent years. Conclusions After a sharp decline in the attractiveness of rheumatology during the last years of the 20th century, there seems to be a recovery.

Aim: To describe the methodology of the EPISER 2016 (study of the prevalence of rheumatic diseases in adult population in Spain), as well its strengths and limitations. The aim of this study is to estimate the prevalence of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), osteoarthritis (knee, hip, hands, and cervical and lumbar spine), fibromyalgia, gout and clinical osteoporotic fracture. Material and method: Population-based, multicenter, cross-sectional study, with the participation of 45 municipalities in the 17 Spanish autonomous communities. The reference population will consist of adults aged 20 years and over residing in Spain. A computer-assisted telephone interview (CATI) system will be used for data collection. Diagnostic suspicions and diagnoses received by the participants will be studied by rheumatologists in the referral hospitals in the selected municipalities. Statistical analysis: the prevalence of the rheumatic diseases will be calculated using estimators and their 95% confidence intervals. Weights will be calculated in each of the sampling stages in accordance with the probability of selection. The distribution of the population in Spain will be obtained from the Spanish Statistics Institute. Conclusions: Sociodemographic and lifestyle changes over the last 16 years justify EPISER 2016. This study will provide current data about the prevalences of RA, AS, PsA, SLE, SS, osteoarthritis, fibromyalgia, gout and clinical osteoporotic fracture. The results will allow comparisons with studies from other countries and EPISER 2000. (C) 2017 Elsevier Espana, S.L.U. and Sociedad Espanola de Reumatologia y Colegio Mexicano de Reumatologia. All rights reserved.

Background:Although ideally Recommendations for the management of rheumatoid arthritis (RA) should be supported by the highest level of evidence, many of which are based on “expert opinion”. This means that there are knowledge gaps to which a part of the research efforts in this disease should be directed.Objectives:1.- Analyze the causes of the low level of evidence in some of the recommendations on diagnosis and management of RA in the main published documents2.- Identify the knowledge gaps that justify said low level of evidence3.- Design actions to respond to the knowledge gaps identified.Methods:Qualitative study. A group of six experts in systematic review of the literature was selected. Fourteen documents of national and international recommendations on RA (EULAR, ACR and SER) of the last 5 years were analyzed by a peer review. They selected recommendations with low level of evidence (Oxford 4 and 5) / grade of recommendation (C and D), and classified by areas (diagnosis, monitoring, treatment, others) and then possible causes of low level of evidence were analyzed. These were submitted to a Delphi to select the 10 recommendations in which participants considered it more critical to obtain quality evidence. Subsequently, actions were proposed to improve the levels of evidence in general and, through the PICOS structure (population, intervention, comparator, study design) specific studies were proposed to respond to the issues raised in these 10 recommendationsResults:185 recommendations were found that had a low level of evidence / grade of recommendation, most related to the treatment of RA. The two most frequent causes of this low level of evidence and / or the degree of recommendation were the absence of studies and an incorrect classification of the level of evidence and / or degree of recommendation. In addition, other reasons and methodological barriers were found for which nine critical recommendations were finally selected for which new PICOs were developed with which to propose targeted research projectsConclusion:It is necessary to improve the methodological approach in the RA recommendations guidelines to correct errors and fill gaps with appropriate studies.Table 1.Actions to increase the level of evidence / recommendation.#Action1Prioritization of research towards knowledge gaps with the design and development of specific studies2Increase knowledge of experts in the methodology of consensus documents (including RSL, formulation of recommendations, etc.)3Supervision of the entire process by expert methodologists, to ensure a correct allocation of the levels of evidence and degree of recommendation4Review and select those topics that are really of interest and should be reviewed and can be answered5Expert opinion should never become a recommendation, but will be included in the text that accompanies that recommendation.6Clear syntax will be used and short recommendations will be made7Establishment and application of homogeneous criteria to formulate recommendationsKey words: Rheumatoid arthritis, recommendations, data gapsDisclosure of Interests:gloria candelas: None declared, Lucía Silva-Fernández: None declared, Maria Montoro Employee of: Pfizer employee, Abad Hernández: None declared, Jose Ramón Maneiro: None declared, Virginia Villaverde: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution), Estíbaliz Loza Grant/research support from: Roche, Pfizer, Abbvie, MSD, Novartis, Gebro, Adacap, Astellas, BMS, Lylly, Sanofi, Eisai, Leo, Sobi, Susana Gómez Employee of: Pfizer employee, Monica Valderrama Consultant of: Pfizer employee, Ana Ortiz: None declared

ObjectivesSince the 2007 recommendations for the management of early arthritis have been presented, considerable research has been published in the field of early arthritis, mandating an update of the 2007 European League Against Rheumatism (EULAR) recommendations for management of early arthritis.MethodsIn accordance with the 2014 EULAR Standardised Operating Procedures, the expert committee pursued an approach that was based on evidence in the literature and on expert opinion. The committee involved 20 rheumatologists, 2 patients and 1 healthcare professional representing 12 European countries. The group defined the focus of the expert committee and target population, formulated a definition of ‘management’ and selected the research questions. A systematic literature research (SLR) was performed by two fellows with the help of a skilled librarian. A set of draft recommendations was proposed on the basis of the research questions and the results of the SLR. For each recommendation, the categories of evidence were identified, the strength of recommendations was derived and the level of agreement was determined through a voting process.ResultsThe updated recommendations comprise 3 overarching principles and 12 recommendations for managing early arthritis. The selected statements involve the recognition of arthritis, referral, diagnosis, prognostication, treatment (information, education, pharmacological and non-pharmacological interventions), monitoring and strategy. Eighteen items were identified as relevant for future research.ConclusionsThese recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis.

Objectives Both TNF inhibitors (TNFi) and rituximab (RTX), a B-cell depleting biologic, can disrupt the immune system in RA. RTX is licensed in Europe for use following TNFi failure. However, safety data on serious infections (SIs) are scarce for RTX in daily practice. This analysis aims to compare the risk of SIs in the first year after a switch to either TNFi or RTX in patients who have failed a first TNFi. Methods This study included patients with RA registered with the British Society for Rheumatology Biologics Register (BSRBR-RA) who switched to either a second TNFi or RTX after failing a first TNFi. Patients were followed until first SI, treatment discontinuation, last recorded follow-up or the end of the first year after the switch, whichever came first. SI was defined as requiring hospitalization, intravenous antibiotics or resulting in death. The risk of first SI was compared between TNFi and RTX using Cox proportional hazard models adjusted using propensity scores using inverse probability of treatment weighting. Results This analysis included 3419 TNFi and 1396 RTX patients contributing 2765 and 1224 person-years (pyrs), respectively. SI occurred in 164 (4.8%) TNFi and 81 (5.8%) RTX patients giving a crude rate of 59 and 66 SI/1000 pyrs, respectively. The adjusted hazard ratio for SI was 1.0 (95% CI: 0.7, 1.4). Conclusion The risk of SIs was comparable over the first year of treatment between TNFi and RTX treatment in patients who had failed a single prior TNFi.

Objective Relapses and failure are frequent in systemic vasculitis (SV) patients. Biological agents have been prescribed as rescue therapies. The aim of this systematic review is to analyze the current evidence on the therapeutic use of biological agents for SV. Methods MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched up to the end of April 2013. Systematic reviews and meta-analysis, clinical trials, cohort studies, and case series with >3 patients were included. Independent article review and study quality assessment was done by 2 investigators with consensus resolution of discrepancies. Results Of 3447 citations, abstracts, and hand-searched studies screened, 90 were included. Most of the studies included ANCA-associated vasculitis (AAV) patients and only a few included large vessel vasculitis (LVV) patients. Rituximab was the most used agent, having demonstrated efficacy for remission induction in patients with AAV. A number of studies used different anti-TNFα agents with contrasting results. A few uncontrolled studies on the use of abatacept, alemtuzumab, mepolizumab, and tocilizumab were found. Conclusion Current evidence on the use of biological therapies for SV is mainly based on uncontrolled, observational data. Rituximab is not inferior to cyclophosphamide for remission induction in AAV and might be superior in relapsing disease. Infliximab and adalimumab are effective as steroid-sparing agents. Etanercept is not effective to maintain remission in patients with granulomatosis with polyangiitis, and serious adverse events have been reported. For LVV, both infliximab and etanercept had a role as steroid-sparing agents, and tocilizumab might be effective also for remission induction in LVV.

Objectives: To explore the influence of tumour necrosis factor inhibitors (TNFi) therapy and rituximab upon the incidence of cancer in patients with rheumatoid arthritis (RA) and prior malignancy.Methods: The study population comprised RA subjects with a prior malignancy reported to the UK national cancer registers, recruited to the British Society for Rheumatology Biologics Register from 2001 to 2013. We compared rates of first incident malignancy in a TNFi-cohort, rituximab-cohort and synthetic disease-modifying antirheumatic drugs (sDMARD) cohort. Results: We identified 425 patients with a prior malignancy from 18,000 RA patients in the study. Of these, 101 patients developed a new malignancy. The rates of incident malignancy were 33.3 events/1,000 person-years in the TNFi cohort, 24.7 events/1,000 person-years in the rituximab cohort and 53.8 events/1,000 person-years in the sDMARD cohort. The age- and gender-adjusted hazard ratio was 0.55 (95% confidence interval 0.35-0.86) for the TNFi cohort and 0.43 (95% confidence interval 0.10 – 1.80)) for the rituximab cohort in comparison with the sDMARDs cohort. The 17.0% of patients in the sDMARDs cohort had a recurrence of the same cancer in comparison with the 12.8% and the 4.3% in the TNFi and rituximab cohorts respectively.Conclusions: Although numbers are still low, it seems that patients with RA and prior malignancy selected to receive either a TNFi or rituximab in the UK do not have an increased risk of future incident malignancy.

Objective To provide a reference to rheumatologists and other physicians involved in the treatment of systemic lupus erythematosus (SLE) who are using, or about to use biologic therapies. Methods Recommendations were developed following a nominal group methodology and based on systematic reviews. The level of evidence and degree of recommendation were classified according to a model proposed by the Center for Evidence Based Medicine at Oxford. The level of agreement was established through a Delphi technique. Results We have produced recommendations on the use of belimumab, the only biological agent with approved indications for SLE, and other biological agents without an indication for SLE. The objective of treatment is to achieve a complete clinical response, taken as the absence of perceived or evident disease activity. Nuances regarding the use of biologic therapies in SLE were reviewed as well, such as the evaluation that should be performed prior to administration and the follow up of patients undergoing these therapies. Conclusions We present the SER recommendations for the use of biological therapies in patients with SLE.

Objetivo Elaborar unas recomendaciones que sirvan de referencia a los reumatologos y otros profesionales implicados en el tratamiento del lupus eritematoso sistemico (LES) que vayan a utilizar o consideren la utilizacion de terapias biologicas en su manejo. Metodos Las recomendaciones se emitieron siguiendo la metodologia de grupos nominales y basadas en revisiones sistematicas. El nivel de evidencia y el grado de recomendacion se clasificaron segun el modelo del Center for Evidence Based Medicine de Oxford y el grado de acuerdo se extrajo por tecnica Delphi. Resultados Se realizan recomendaciones sobre el uso de belimumab, actualmente unica terapia biologica con aprobacion para el tratamiento del LES, y otras terapias biologicas sin indicacion aprobada en LES. El objetivo del tratamiento es la respuesta clinica completa, entendida como la ausencia de actividad clinica percibida o constatable. Se matiza el uso de terapias biologicas en LES y cual debe ser la evaluacion previa y la vigilancia del paciente que recibe estos farmacos. Conclusiones Se presentan las recomendaciones SER sobre el uso de terapias biologicas en el LES.

Corticosteroids are a mainstay in the therapy of rheumatoid arthritis (RA). In recent years, a number of high-quality controlled clinical trials have shown their effect as a disease-modifying anti-rheumatic drug (DMARD) and a favorable safety profile in recent-onset RA. Despite this, they are more frequently used as bridge therapy while other DMARDs initiate their action than as true disease-modifying agents. Low-dose corticosteroid use during the first two years of disease slows radiologic damage and reduces the need of biologic therapy aimed at reaching a state of clinical remission in recent-onset RA. Thus, their systematic use in this clinical scenario should be considered.

Los glucocorticoides son un componente fundamental en el tratamiento de la artritis reumatoide (AR). En los ultimos anos, numerosos ensayos clinicos controlados de alta calidad metodologica han demostrado su accion como farmaco antirreumatico modificador de enfermedad (FAME) y un favorable perfil de seguridad en la AR de reciente comienzo. No obstante, es frecuente que se utilicen mas como terapia puente hasta que otros FAME comienzan a actuar que como autenticos agentes modificadores de enfermedad. Los glucocorticoides a dosis bajas durante los 2 primeros anos de la enfermedad frenan el deterioro radiologico y reducen la necesidad de usar agentes biologicos para conseguir la remision clinica en la AR de inicio por lo que se deberia valorar su utilizacion sistematica en este contexto clinico

a b s t r a c t Purpose: To determine the efficacy and safety of denosumab in osteoporosis. Methods: A systematic search was performed in MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials (1950 to July 2010), meeting abstracts (2009-2010), trial registries, and reference lists. The selection criteria were as follows: (population) osteoporosis patients of any age; (intervention) treatment with denosumab; (outcome) efficacy and safety; (study design) randomized clinical trials (RCTs); no language restrictions. Two reviewers independently screened titles and abstracts and subse- quently extracted data from the selected studies including quality items, and on outcomes of interest. A meta-analysis was performed for safety issues. Results: A total of 25 studies were included. Denosumab reduces the risk of new radiographic vertebral fracture in a 68% compared with placebo (p < 0.001) and increases bone mineral density (BMD) at lumbar spine, total hip, and one-third radius more than alendronate and placebo. A single subcutaneous dose of denosumab resulted in a dose-dependent, rapid, profound, and sustained decrease bone turnover markers (BTMs). Denosumab was in general well tolerated. A meta-analysis has shown an increase in the incidence of urinary infections (p = 0.012) and eczema (p < 0.001) in the patients treated with denosumab. Meta-analysis of efficacy was complicated due to the study features. Conclusions: Denosumab given subcutaneously twice yearly is associated with a reduction in the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis. Denosumab is associated with greater and sustained increases in BMD and reductions in BTMs compared with placebo and/or alendronate and with a risk of urinary infections and eczema.

The aim of this work was to assess the variability in the use of health-care resources, based on the number of visits to rheumatology departments by rheumatoid arthritis patients, in Spain, and its association with patient, physician and center characteristics. The sample consisted of patient records of men and women (aged 16 or older), with a clinical diagnosis of RA, who met the American Rheumatism Association 1987 revised criteria and who had been treated in a rheumatology department at a Spanish hospital with at least one visit to a rheumatologist during the two years preceding the date of the study. To analyze which variables were independently associated with the number of consultations, those with a statistically significant result in the bivariate analysis, or which were clinically relevant or deemed confounders, were used in the construction of a linear regression model. The records of 1188 RA patients were studied. The linear regression model explained the 26.67 % of the variability in the number of visits. The number of csDMARDs prescribed, the administration of biological therapy, corticoid prescription, the presence of nursing consultation, mean time to first visit in the department and attended population showed a positive significant association, while the presence of telephone consultation, distance from the hospital to the patient´s residence (≥20 km) and drug monitoring by rheumatology department + primary care physician or by other specialists were negatively associated with the number of consultations. We observed a high variability in the number of visits, which remains partially unexplained even after taking into account individual, physician and center characteristics.

Objectives. To identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality. Methods. This is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years. Results. Three damage clusters were identified. Cluster (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 10096 in clusters 2 and 3. P < 0.001). Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 0.096 of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P < 0.001 for both comparisons) and in patients with disease duration shorter than 5 years as well. Conclusion. In a large cohort of SLE patients, cardiovascular and musculoskeletal damage manifestations were the two dominant forms of damage to sort patients into clinically meaningful clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems.

OBJECTIVES: To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort. METHODS: All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ?4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection. RESULTS: A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ?1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6-30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection (p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009-1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539-3.005), corticosteroids (?10mg/day) (HR = 1.271, 95% CI: 1.034-1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079-1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905-3.459), Katz severity index (HR = 1.160, 95% CI: 1.105-1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031-1.108), and smoking (HR = 1.332, 95% CI: 1.121-1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997-0.999). CONCLUSIONS: Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect. Spanish Foundation of Rheumatology. FIS/ISCIII (grant number PI11/02857). Dr. Pego-Reigosa is supported by Grant 316265 (BIOCAPS) from the European Union 7th Framework Programme (FP7/REGPOT-2012–2013.1).

A biomarker is a biological parameter that can be measured in blood or other body fluids or tissues and used as a sign of a normal or abnormal process, or of a condition or disease. In medicine, a biomarker can be used to diagnose a disease, to establish its prognosis or as a surrogate marker of outcome in research. In recent years, there has been strong interest in discovering new biomarkers, as well as in the development of new uses for well-known biomarkers in distinct diseases. In this article, the utility of several biomarkers not routinely used in rheumatology (procalcitonin, natriuretic peptides and cardiac troponins) in the diagnosis and follow-up of patients with systemic autoimmune diseases is reviewed.

Objective. To critically appraise the validity of activity indices used in the followup of patients with undifferentiated peripheral inflammatory arthritis (UPIA). Methods. A systematic review was performed in Medline, Embase, the Cochrane Library, and abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology and European League Against Rheumatism. Selection criteria were: patients with UPIA, the assessment of instruments to evaluate disease activity, and assessment of validity of the instruments. Two reviewers screened titles and abstracts independently and collected data using ad hoc standard forms. Results. The search yielded 179 articles and 834 abstracts, of which 4 articles and 1 abstract were included. We found no study that validated Disease Activity Score (DAS), Clinical Disease Activity Index (CDAI), or Simplified Disease Activity Index (SDAI). Included studies addressed validation of 4 questionnaires: WHO Disability Assessment Schedule (WHODAS), London Handicap Scale (LHS), Disease Repercussion Profile (DRP), and the Health Assessment Questionnaire (HAQ); and 3 indexes: RA Disease Activity Index (RADAI), McGill Range of Motion Index (McROMI), and NOAR Damaged Joint Count (NOAR-DJC). Questionnaires were self-administered and feasible; RADAI was the most feasible index. Internal consistency was studied in the questionnaires (Cronbach’s α > 0.83). Responsiveness was tested in the DRP, LHS, and HAQ, but the approach to study sensitivity to change was poorly explained, with no clear intervention. Construct validity, examined by means of convergence with other instruments, was generally moderate, and slightly higher for the RADAI. Conclusion. No instrument of disease activity has been fully validated for use in UPIA. We found no direct evidence of what is the most useful index to follow up patients with UPIA.

Some occupational factors have been implicated in the development of disorders manifested as hand pain. The associations seem to be well documented in processes such as hand-arm vibration syndrome (HAVS) or writer's cramp. There are contradictory data in the literature about the relationships of trigger finger, De Quervain's tenosynovitis (DQT) and tenosynovitis of the wrist with occupational factors. In this article, we review current knowledge about clinical manifestations, case definition, implicated occupational factors, diagnosis and treatment of the most relevant hand pain disorders that have been associated with occupational factors, excluding carpal tunnel syndrome (CTS).

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. Autoantibody production plays a critical role in its pathogenic pathways. Thus, B-cell directed biologic therapy is a logical option. The present article reviews the latest advances in the development of B-cell directed biological agents in the treatment of SLE. Rituximab has been studied in a number of open series of patients that suggest efficacy but two recent controlled clinical trials have failed to show efficacy versus placebo. In contrast, a recent placebo-controlled, double-blind, randomized trial has reported that belimumab has statistically significant efficacy versus placebo. Atacicept, a fusion protein that blocks cytokines that play a critical role in the differentiation and survival of B-cells and plasma cells, markedly reduces autoantibody levels but could increase the risk of infection. Further studies are needed to establish the role of B-cell directed biologic therapy in SLE.

What is the best rheumatoid arthritis therapy after failure of a first anti-TNF drug? No consensus has been reached on whether to switch to rituximab or an alternative TNF inhibitor. New observational studies suggest that either course can be effective. But are more data needed?

Shoulder pain is one of the most common presenting complaints in daily clinical practice. The assessment of patients with shoulder pain is usually complicated due to the wide variety of possible etiologies. Physical examination of the shoulder is especially important in the assessment of soft tissue disorders, since there are a number of physical examination manoeuvres specifically designed to examine particular structures. In this article, the various clinical tests and their diagnostic utility for examining subacromial impingement, supraspinatus, infraspinatus, subscapularis and biceps tendons, gleno-humeral instability and the acromioclavicular joint are reviewed and compared with procedures considered as the gold standard.