The enzymatic properties of Arabidopsis thaliana DNA polymerase λ suggest a role in base excision repair.

Base excision repair (BER) generates gapped DNA intermediates containing a 5'-terminal 2-deoxyribose-5-phosphate (5'-dRP) group. In mammalian cells, gap filling and dRP removal are catalyzed by Pol ß, which belongs to the X family of DNA polymerases. In higher plants, the only member of the X family of DNA polymerases is Pol λ. Although it is generally believed that plant Pol λ participates in BER, there is limited experimental evidence for this hypothesis. Here we have characterized the biochemical properties of Arabidopsis thaliana Pol λ (AtPol λ) in a BER context, using a variety of DNA repair intermediates. We have found that AtPol λ performs gap filling inserting the correct nucleotide, and that the rate of nucleotide incorporation is higher in substrates containing a C in the template strand. Gap filling catalyzed by AtPol λ is most efficient with a phosphate at the 5'-end of the gap and is not inhibited by the presence of a 5'-dRP mimic. We also show that AtPol λ possesses an intrinsic dRP lyase activity that is reduced by mutations at two lysine residues in its 8-kDa domain, one of which is present in Pol λ exclusively and not in any Pol ß homolog. Importantly, we also found that the dRP lyase activity of AtPol λ allows efficient completion of uracil repair in a reconstituted short-patch BER reaction. These results suggest that AtPol λ plays an important role in plant BER.

The C-terminal domain of Arabidopsis ROS1 DNA demethylase interacts with histone H3 and is required for DNA binding and catalytic activity.

Active DNA demethylation plays an important role in controlling methylation patterns in eukaryotes. In plants, the DEMETER-LIKE (DML) family of 5-methylcytosine DNA glycosylases initiates DNA demethylation through a base excision repair pathway. However, it is poorly understood how these DNA demethylases are recruited to their target loci and the role that histone marks play in this process. Arabidopsis REPRESSOR OF SILENCING 1 (ROS1) is a representative enzyme of the DML family, whose members are uniquely characterized by a basic amino-terminal domain mediating nonspecific binding to DNA, a discontinuous catalytic domain, and a conserved carboxy-terminal domain of unknown function. Here, we show that ROS1 interacts with the N-terminal tail of H3 through its C-terminal domain. Importantly, phosphorylation at H3 Ser28, but not Ser10, abrogates ROS1 interaction with H3. Conserved residues at the C-terminal domain are not only required for H3 interaction, but also for efficient DNA binding and catalytic activity. Our findings suggest that the C-terminal domain of ROS1 may function as a histone reader module involved in recruitment of the DNA demethylase activity to specific genomic regions.

[Cost-minimization analysis of subcutaneous abatacept in the treatment of rheumatoid arthritis in Spain]. / Análisis de minimización de costes de abatacept subcutáneo en el tratamiento de la artritis reumatoide en España.

OBJECTIVE: To compare the cost of treating rheumatoid arthritis patients that have failed an initial treatment with methotrexate, with subcutaneous abatacept versus other first-line biologic disease-modifying antirheumatic drugs. METHOD: Subcutaneous abatacept was considered comparable to intravenous abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab and tocilizumab, based on indirect comparison using mixed treatment analysis. A cost-minimization analysis was therefore considered appropriate. The Spanish Health System perspective and a 3 year time horizon were selected. Pharmaceutical and administration costs (Euros 2013) of all available first-line biological disease-modifying antirheumatic drugs were considered. Administration costs were obtained from a local costs database. Patients were considered to have a weight of 70 kg. A 3% annual discount rate was applied. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Subcutaneous abatacept proved in the base case to be less costly than all other biologic antirrheumatic drugs (ranging from Euros -831.42 to Euros -9,741.69 versus infliximab and tocilizumab, respectively). Subcutaneous abatacept was associated with a cost of Euros 10,760.41 per patient during the first year of treatment and Euros 10,261.29 in subsequent years. The total 3-year cost of subcutaneous abatacept was Euros 29,953.89 per patient. Sensitivity analyses proved the model to be robust. Subcutaneous abatacept remained cost-saving in 100% of probabilistic sensitivity analysis simulations versus adalimumab, certolizumab, etanercept and golimumab, in more than 99.6% versus intravenous abatacept and tocilizumab and in 62.3% versus infliximab. CONCLUSIONS: Treatment with subcutaneous abatacept is cost-saving versus intravenous abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab and tocilizumab in the management of rheumatoid arthritis patients initiating treatment with biological antirheumatic drugs.

OBJETIVO: Comparar, desde la perspectiva del Sistema Sanitario, el coste del tratamiento con abatacept subcutáneo en pacientes con artritis reumatoide tras fracaso a metotrexato, frente al resto de fármacos antirreumáticos modificadores de la enfermedad disponibles en España con indicación en primera línea de terapia biológica. MÉTODOS: Una comparación indirecta demostró eficacia y seguridad de abatacept subcutáneo comparables a abatacept intravenoso, adalimumab, certolizumab, etanercept, golimumab, infliximab y tocilizumab, por lo que se optó por una minimización de costes. El análisis incluyó costes farmacológicos y de administración (, 2013) para un paciente "tipo" de 70 kg y un horizonte temporal de tres años. Se aplicó una tasa anual de descuento del 3%. Se realizaron análisis de sensibilidad determinísticos y probabilísticos. RESULTADOS: Abatacept subcutáneo tuvo un coste anual de 10.760,41 durante el primer año, 10.261,29 en los años siguientes, y un coste total de 29.953,89 a los tres años, generando ahorros (rango -831,41 versus infliximab a -9.741,69 versus tocilizumab) frente a los demás antirreumáticos modificadores de la enfermedad. Las mayores diferencias entre fármacos se observaron durante el primer año de tratamiento. Abatacept subcutáneo se asoció a ahorros en el 100% de las simulaciones del análisis de sensibilidad probabilístico versus adalimumab, certolizumab, etanercept y golimumab, en más del 99,6% versus abatacept intravenoso y tocilizumab y en el 62,3% versus infliximab. CONCLUSIONES: En base a los resultados, el tratamiento con abatacept subcutáneo genera ahorros frente a abatacept intravenoso, adalimumab, certolizumab, etanercept, golimumab, infliximab y tocilizumab en pacientes con artritis reumatoide que inician tratamiento con fármacos antirreumáticos biológicos.

Análisis de minimización de costes de abatacept subcutáneo en el tratamiento de la artritis reumatoide en España / Cost-minimization analysis of subcutaneous abatacept in the treatment of rheumatoid arthritis in Spain

Objetivo: Comparar, desde la perspectiva del Sistema Sanitario, el coste del tratamiento con abatacept subcutáneo en pacientes con artritis reumatoide tras fracaso a metotrexato, frente al restode fármacos antirreumáticos modificadores de la enfermedad disponibles en España con indicación en primera línea de terapia biológica. Métodos: Una comparación indirecta demostró eficacia y seguridad de abatacept subcutáneo comparables a abatacept intravenoso, adalimumab, certolizumab, etanercept, golimumab, infliximab y tocilizumab, por lo que se optó por una minimización de costes. El análisis incluyó costes farmacológicos y de administración (Euros, 2013) para un paciente "tipo" de 70 kg y un horizonte temporal de tres años. Se aplicó una tasa anual dedescuento del 3%. Se realizaron análisis de sensibilidad determinísticos y probabilísticos. Resultados: Abatacept subcutáneo tuvo un coste anual de 10.760,41 Euros durante el primer año, 10.261,29 Euros en los años siguientes, y un coste total de 29.953,89 Euros a los tres años, generando ahorros (rango -831,41 € versus infliximab a -9.741,69 € versus tocilizumab) frente a los demás antirreumáticos modificadores de la enfermedad. Las mayores diferencias entre fármacos se observaron durante el primer año de tratamiento. Abatacept subcutáneo se asoció a ahorros en el 100% de las simulaciones del análisis de sensibilidad probabilístico versus adalimumab, certolizumab, etanercept y golimumab, en más del 99,6% versus abatacept intravenoso y tocilizumab y en el 62,3% versus infliximab. Conclusiones: En base a los resultados, el tratamiento con abatacept subcutáneo genera ahorros frente a abatacept intravenoso, adalimumab, certolizumab, etanercept, golimumab, infliximab y tocilizumab en pacientes con artritis reumatoide que inician tratamiento con fármacos antirreumáticos biológicos

Objective: To compare the cost of treating rheumatoid arthritis patients that have failed an initial treatment with methotrexate, with subcutaneous aba tacept versus other first-line biologic disease-modifying antirheumatic drugs. Method: Subcutaneous abatacept was considered comparable to intravenous abatacept, adalimumab, certolizumab pegol, etanercept, golimumab,infliximab and tocilizumab, based on indirect comparison using mixed treatment analysis. A cost-minimization analysis was therefore considered appropriate. The Spanish Health System perspective and a 3 year time horizon were selected. Pharmaceutical and administration costs (Euros ,2013) of all available first-line biological disease-modifying antirheumatic drugs were considered. Administration costs were obtained from a local costs database. Patients were considered to have a weight of 70 kg. A 3%annual discount rate was applied. Deterministic and probabilistic sensitivity analyses were performed. Results: Subcutaneous abatacept proved in the base case to be less costly than all other biologic antirrheumatic drugs (ranging from € -831.42 to € -9,741.69 versus infliximab and tocilizumab, respectively). Subcutaneous abatacept was associated with a cost of € 10,760.41 per patient during the first year of treatment and €10,261.29 in subsequent years. The total 3-year cost of subcutaneous abatacept was € 29,953.89 per patient. Sensitivity analyses proved the model to be robust. Subcutaneous abatacept remained cost-saving in 100% of probabilistic sensitivity analysis simulations versus adalimumab, certolizumab, etanercept and golimumab, in more than 99.6% versus intravenous abatacept and tocilizumab and in 62.3% versus infliximab. Conclusions: Treatment with subcutaneous abatacept is cost-saving versus intravenous abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab and tocilizumab in the management of rheumatoid arthritis patients initiating treatment with biological antirheumatic drugs

Neoliberalismo en salud: La tortura de trabajadoras y trabajadores del Instituto Materno Infantil de Bogotá / Neoliberalism in health: the torture of the health care workers of the Bogota s Instituto Materno Infantil (child and maternity hospital)

Objetivos Relacionar históricamente las transformaciones más significativas del Instituto Materno Infantil (IMI) en su proceso de crisis, cierre y liquidación con las experiencias de sus trabajadores/as. Encontrar elementos vivenciales y teóricos que interconecten el proceso de privatización de la salud con las experiencias de resistencia y dolor/sufrimiento de trabajadores/as. Métodos Etnografía inscrita en corrientes críticas y apoyada en trabajo de campo constante y colectivo, investigación histórica (fuentes primarias y secundarias) y entrevistas semiestructuradas con cinco mujeres que trabajaron por más de quince años en el IMI. Resultados Una línea del tiempo con cuatro periodos principales: Los años de gloria (hasta 1990), Llega el neoliberalismo (1990-2000), La crisis y las resistencias (2001-2005) y Liquidación (2006-). La narrativa de las mujeres entrevistadas devela múltiples agresiones que se intensificaron desde el 2006 generando dolor/ sufrimiento, relatos que ilustran violaciones a sus derechos humanos y laborales. Discusión Proponemos analizar las conexiones entre los diferentes tipos de violencia y el dolor/sufrimiento bajo la categoría tortura, entendida como acciones violentas que causan dolor físico-emocional, las cuales son ejecutadas por actores de poder sobre otros que desafían alterarlo. Enfatizamos en las burocracias, el confinamiento, los agentes torturadores y los resquebrajamientos a la unidad mente/cuerpo para argumentar que esta relación neoliberalismo y tortura pretende eliminar los últimos trabajadores/as de la salud del país con garantías laborales para avanzar en la acumulación de capital que genera la creciente sobreexplotación del trabajo y la mercantilización de la salud.

Objectives To link, from a historical point of view, the most significant transformations of the Instituto Materno Infantil (IMI) [the oldest child and maternity hospital of the country] during its process of crisis, closure and liquidation with the experiences of the hospital workers. To find experience-based and theoretical elements that can interconnect the process of health care privatization of the country with the workers' experiences of resistance and pain/suffering. Methods Critically-oriented ethnography based on continuous collective field work, historical research (primary and secondary sources) and semi-structured interviews with 5 women who worked at the IMI for more than 15 years.Results: A time line of 4 main periods: Los años de gloria [The golden years] (up to 1990); Llega el neoliberalismo [Neoliberalism arrives] (1990-2000); La crisis y las resistencias [Crisis and resistances] (2001-2005); and Liquidación [Liquidation (2006-20??)]. The narratives of the interviewed women unveil multiple aggressions that have intensified since 2006, have caused pain and suffering and are examples of violations of human and labour rights. Discussion We suggest to analyze the links between the different kinds of violence and pain and suffering as torture. This category is defined as the set of violent actions that cause physical and emotional pain, which are performed by actors in positions of power over other people who challenge that power and are part of modern States' ideological principles around a defined moral social order. For the IMI workers' case, the ideological principle that is being challenged is health care neoliberalism. From the analyses of bureaucracy, confinement, torturing agents, and the breaking-off of the body-mind unit we conclude that this relationship between neoliberalism and torture aims to eliminate the last health care workers of the country who had job stability and full-benefits through public labour contracts. Their elimination furthers the accumulation of capital generated by increasing over-exploitation of labour and commodification of health care.

Fibromyalgia in patients with ankylosing spondylitis: prevalence and utility of the measures of activity, function and radiological damage.

OBJECTIVES: To determine the prevalence of fibromyalgia (FM) in ankylosing spondylitis (AS). To evaluate the effect of FM on the measures of activity in AS. To analyse predictive factors in order to identify this group of patients. PATIENTS AND METHODS: A cross-sectional study based on 462 patients with definite ankylosing spondylitis included in the REGISPONSER. Sociodemographic data, clinical features, Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS radiology index (BASRI), Stoke modified index (Sasss-m), laboratory data, Short-Format 12 (SF-12), AS specific quality of life (ASQoL), Fibromyalgia Impact Questionnaire (FIQ) and treatments used were all documented. To diagnose FM, the ACR 1990 criteria had to be fulfilled. All statistical tests were performed using STATA. RESULTS: The prevalence of fibromyalgia in all AS was 4.11%. Among the women with AS, the prevalence of FM increased to 10.83%. The BASDAI, BASFI and total BASRI were strongly influenced by the presence of FM. The inverse relationship between BASDAI or BASFI and total BASRI was taken to generate a ratio. Accordingly, if the patient presented BASDAI/BASRI ≥1.5 or BASFI/BASRI ≥1.08, the probability of having FM was very high. CONCLUSIONS: There is an increased risk of FM in females with AS. The fact of having FM distorts the measures of activity and functional damage of AS. As a result, it is possible that some patients with AS and FM are being overtreated. The BASDAI/BASRI and BASFI/BASRI ratios are very useful to identify these patients.

Relationship between spinal mobility and disease activity, function, quality of life and radiology. A cross-sectional Spanish registry of spondyloarthropathies (REGISPONSER).

OBJECTIVE: To determine the relationship between anthropometric measurements and disease activity, functional capacity, quality of life and radiology in Spanish patients with ankylosing spondylitis (AS). PATIENTS AND METHODS: A cross-sectional study was made of 842 patients with definite ankylosing spondylitis (REGISPONSER). Sociodemographic data, spinal mobility measurements, Bath AS disease activity index (BASDAI), nocturnal pain, Bath AS radiology index (BASRI), Bath AS functional index (BASFI), the Short-Format 12 (SF-12) and the AS specific quality of life (ASQoL) questionnaire were applied. Pearson correlation coefficient analysis and regression models were constructed. RESULTS: There was moderate correlation between fingertip-to-floor distance and lateral cervical rotation with the BASFI (p<0.01). Good correlation was evident between wall-occiput distance and lateral cervical rotation with the BASRI (p<0.01). Moderate correlation was found between chest expansion, the Schober modified test and fingertip-to-floor distance with the total BASRI (p<0.01). The anthropometric measurement with the lowest correlation value was lateral lumbar flexion. Significant association was found between the Schober modified test and BASFI, BASDAI and BASRI (R(2) = 0.37; p<0.001); chest expansion and BASFI, BASDAI and BASRI (R(2) = 0.25; p<0.001); wall-occiput distance and BASFI, BASRI and ASQoL (R(2) = 0.44; p<0.001); fingertip-to-floor distance and BASFI and BASRI (R(2) = 0.30; p<0.001); and lateral cervical rotation and BASFI and BASRI (R(2) = 0.34; p<0.001). CONCLUSION: In our study, wall-occiput distance and lateral cervical rotation showed the strongest correlation to BASRI. Similarly, fingertip-to-floor distance and lateral cervical rotation exhibited the closest correlation to BASFI.

Dose escalation of the anti-TNF-alpha agents in patients with rheumatoid arthritis. A systematic review.

OBJECTIVE: To estimate the proportion of rheumatoid arthritis (RA) patients on anti-tumour necrosis factor (anti-TNF) who require dose escalation. METHODS: Systematic review of the scientific literature. Infliximab, etanercept and adalimumab studies in RA were considered. Primary outcome was the proportion of patients requiring dose escalation. American College Rheumatology (ACR) and Disease activity score (DAS) responses post-escalation were assessed when available. RESULTS: From 1801 references, 16 studies with 8510 patients were included. Of all the infliximab patients, 53.7% underwent dose escalation. Fourty-four per cent of the infliximab patients experienced dose increase and 8.3%, frequency increase. The ACR20 response to dose escalation ranged from 27 to 36% and DAS28 improved from 5.2 to 4.5 in one study and from 4.1 to 3.7 in another. Of the etanercept patients, 17.5% experienced a dose increase but changes on the mean dose were not statistically significant. CONCLUSIONS: Dose escalation is common in patients treated with infliximab, and less frequent with etanercept. In a proportion of patients, the dose escalation seems effective. The design and evidence level of the available studies limit the strength of the conclusions.

Adaptación transcultural y validación de una versión en español de un instrumento específico para medir calidad de vida relacionada con la salud en pacientes con espondilitis anquilosante: el ASQoL / Cross-cultural adaptation and validation of a Spanish version of a specific instrument to measure health-related quality of life in patients with ankylosing spondylitis

Objetivo: Adaptación transcultural y validación de la versión en español del Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL). Pacientes y métodos: Estudio transversal con prueba testretest. Se incluyeron pacientes con espondilitis anquilosante (EA). Se realizó adaptación transcultural de la versión original del ASQoL mediante traducción y retrotraducción. Se estudiaron validez de constructo, consistencia interna, reproducibilidad y factibilidad. El análisis estadístico se realizó con el coeficiente de correlación de Spearman, la pruebas U de Mann- Whitney y Kruskal-Wallis, el coeficiente alfa de Cronbach y el estadístico kappa. Resultados: Se incluyeron 54 pacientes, 37 (68,5%) varones, con edad (promedio ± DE) 40,5 ± 10,5 años. El ASQoL tuvo una puntuación de 6,8 ± 4,7 (mediana, 7; intervalo, 0-17) y presentó correlaciones altas con los componentes globales físico (rho = 0,79) y mental (0,69) del SF-36 y con los dominios de dolor (0,82), vitalidad (0,75) y rol físico (0,68), así como con la mayoría de variables representativas de la EA. Las puntuaciones del ASQoL fueron significativamente diferentes entre los pacientes con distintos niveles de respuesta en el perfil de salud del EuroQol. El ASQoL tuvo un coeficiente alfa de Cronbach de 0,86. La prueba test-retest se realizó en 10 pacientes con un intervalo de 24 h y tuvo una kappa entre 1 (12 preguntas) y 0,57 (1 pregunta) con rho de 0,98 para las puntuaciones globales. El tiempo empleado osciló entre 2 y 5 min. Conclusiones: La versión en español del ASQoL es válida, fiable y factible de aplicar en nuestro medio para medir la calidad de vida de los pacientes con EA(AU)

Objective: To make a cross-cultural adaptation and validation of a version in Spanish of the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) for assessing the health-related quality of life (HRQL) of patients with Ankylosing Spondylitis (AS). Patients and methods: A cross-sectional study with test-retest. AS patients (modified New York criteria) were included. Cross-cultural adaptation was done. Construct validity was assessed comparing the ASQoL scores with the SF-36 and EuroQol scores and diseaserelated variables. Internal consistency and reliability (test-retest) were assessed. Feasibility was assessed by the time spent to complete the questionnaire and the number of items without answer. Spearman correlation coefficient, Mann-Whitney U test, and Kruskal-Wallis test were used in the statistical analysis. Cronbach´alpha coefficient and statistic kappa were used for assessing internal consistency and reliability. Results: Fifty-four patients, 37 males (68.5%), with age (mean±SD) 40.5 ± 10.5 years, were included. The ASQoL global score was 6.8 ± 4.7 (median, 7; range, 0-17). The ASQoL scores had high correlations with physical (rho = 0.79) and mental (0.69) SF-36 components, the SF-36 domains pain (0.82), vitality (0.75), and role-physical (0.68), and the most of the disease-related variables. The ASQoL scores were significantly different between patients with different response levels in the health profile of the EuroQol. The Cronbach´alpha coefficient was 0.86. The reliability had kappa = 1 in 12 items and rho = 0.98. The time spent to complete the ASQoL was from 2 to 5 minutes and there only was a missing answer in one patient. Conclusion: The Spanish ASQoL is valid, reliable, and feasible instrument for assessing the HRQL of the AS patients(AU)

[Cross-cultural adaptation and validation of a Spanish version of a specific instrument to measure health-related quality of life in patients with ankylosing spondylitis]. / Adaptación transcultural y validación de una versión en español de un instrumento específico para medir calidad de vida relacionada con la salud en pacientes con espondilitis anquilosante: el ASQoL.

OBJECTIVE: To make a cross-cultural adaptation and validation of a version in Spanish of the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) for assessing the health-related quality of life (HRQL) of patients with Ankylosing Spondylitis (AS). PATIENTS AND METHODS: A cross-sectional study with test-retest. AS patients (modified New York criteria) were included. Cross-cultural adaptation was done. Construct validity was assessed comparing the ASQoL scores with the SF-36 and EuroQol scores and diseaserelated variables. Internal consistency and reliability (test-retest) were assessed. Feasibility was assessed by the time spent to complete the questionnaire and the number of items without answer. Spearman correlation coefficient, Mann-Whitney U test, and Kruskal-Wallis test were used in the statistical analysis. Cronbach́alpha coefficient and statistic kappa were used for assessing internal consistency and reliability. RESULTS: Fifty-four patients, 37 males (68.5%), with age (mean±SD) 40.5±10.5 years, were included. The ASQoL global score was 6.8±4.7 (median, 7; range, 0-17). The ASQoL scores had high correlations with physical (rho = 0.79) and mental (0.69) SF-36 components, the SF-36 domains pain (0.82), vitality (0.75), and role-physical (0.68), and the most of the disease-related variables. The ASQoL scores were significantly different between patients with different response levels in the health profile of the EuroQol. The Cronbach́alpha coefficient was 0.86. The reliability had kappa = 1 in 12 items and rho = 0.98. The time spent to complete the ASQoL was from 2 to 5 minutes and there only was a missing answer in one patient. CONCLUSION: The Spanish ASQoL is valid, reliable, and feasible instrument for assessing the HRQL of the AS patients.

Análisis de costes en una cohorte de enfermos con artritis reumatoide atendidos en área especializada de reumatología en España / Cost analysis in a cohort of rheumatoid arthritis patients managed in rheumatology units in Spain

Objetivo: Conocer los costes generados durante un año por pacientes con artritis reumatoide (AR) atendidos en unidades de reumatología de hospitales públicos españoles. Métodos: Estudio observacional, multicéntrico, longitudinal y prospectivo, de un año de duración, realizado en unidades de reumatología de hospitales públicos españoles seleccionados de forma probabilística. Los pacientes con AR se seleccionaron aleatoriamente en cada hospital. Se realizaron 4 visitas (basal y cada 4 meses). Se registró la utilización de recursos y costes mediante diarios y entrevistas estructuradas. Resultados: Se incluyó a 301 pacientes y completaron 190 (83% mujeres), con edad (media ± DE) de 59 ± 13 años y duración de la enfermedad de 10 ± 10 años. El coste mediano anual por paciente fue de 3.845 euros (318- 36.783). El coste global anual estimado para la AR atendida en unidades de reumatología de hospitales públicos españoles es de 590.110.000 euros. De los costes globales, el 74% correspondió a costes directos y el 26% a costes indirectos. El 81% del coste directo fue por gasto médico y, de éste, el 56%, por fármacos y el 11%, por hospitalización, el 21% correspondió a visitas médicas y el 12%, a pruebas de laboratorio y complementarias. El principal componente del coste indirecto fue la invalidez, que supuso el 66% del total. Conclusión: El coste directo de la AR fue sustancialmente mayor que el indirecto. El coste por medicamentos fue el principal componente del coste. El coste anual por paciente tuvo un rango muy amplio debido a la gran variabilidad en la utilización de recursos(AU)

Objective: To assess the annual costs of rheumatoid arthritis (RA) patients attended at rheumatology units in Spanish public hospitals. Methods: A longitudinal, prospective, multicenter, observational, 1-year study was performed in the rheumatology units of randomly selected Spanish public hospitals. Randomly selected RA patients were included. The patients made four visits (at baseline and every 4 months). Resource use and costs were collected from patient diaries and structured questionnaires. Results: A total of 301 patients were included and 190 (83% women) completed the study. The mean (± SD) age was 59 ± 13 years and the mean disease duration was 10 ± 10 years. The median annual cost per patient was 3,845 euros (318-36,783). The estimated total annual cost of the Spanish RA population managed in the rheumatology units of public hospitals was 590,110,000 euros. Of total costs, 74% were direct costs and 26% were indirect costs. Medical costs represented 81% of direct costs. The main components of medical costs were drugs (56%), medical visits (21%), complementary tests (12%), and hospitalizations (11%). Permanent work disability represented 66% of indirect costs. Conclusions: Direct costs were substantially higher than indirect costs. The main components of medical costs were drugs. There was high variability in resource use with a wide range of annual costs per patient(AU)

Adalimumab for treating rheumatoid arthritis.

BACKGROUND: Adalimumab is a fully human anti-TNFalpha monoclonal antibody. Published studies indicate that its use in patients with RA can be effective and safe. OBJECTIVES: The aim of this review was to assess the efficacy and safety of adalimumab in the treatment of RA. SEARCH STRATEGY: Electronic databases were searched up to August, 2004: MEDLINE, CINAHL, EBM Reviews (CDSR, ACP Journal Club, DARE and CENTRAL) and Health STAR. Conference proceedings were hand searched and pharmaceutical companies were contacted to obtain additional unpublished data from published trials. Adalimumab was searched as a text word as it is not currently indexed. The search was not limited by language, year of publication or type of publication. SELECTION CRITERIA: All randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing adalimumab alone or in combination with DMARDs to placebo or other DMARDs. DATA COLLECTION AND ANALYSIS: Two reviewers independently collected the data in a standardized form and assessed the methodological quality of the trial using validated criteria. Outcome measures included ACR and EULAR responses, DAS 28 and components of ACR response and radiographic data. Safety data were also included. Continuous data were reported as weighted mean difference (WMD) with 95% confidence interval (95%CI), absolute benefit (AB) and relative difference (RD). Dichotomous outcomes were reported as relative risk (RR) with 95% CI, absolute risk difference (ARD) or risk difference (RDiff) with 95%CI and number needed to treat (NNT) or to harm (NNH). When significant heterogeneity was not found, data were pooled. MAIN RESULTS: Six studies with 2381 patients were included in this review. Two comparisons were done: A. adalimumab subcutaneously (sc) + methotrexate (or DMARDs) versus placebo sc + methotrexate (or DMARDs). B. adalimumab sc in monotherapy versus placebo sc. In the comparison A, with adalimumab 40 mg every other week (e.o.w.), the RR to achieve an ACR 20 response at 24 weeks ranged in the included studies from 1.52 to 4.63, and the NNT ranged from 1.9 to 5.4. The RR (95%CI) to achieve an ACR 50 response was 4.63 (3.04-7.05), and the NNT was 3.0 (95%CI 2.0-6.0). The RR (95%CI) to achieve an ACR 70 response was 5.14 (3.14-8.41) and the number needed to treat was 7.0 (95%CI 5.0-13.0). At 52 weeks, the RRs (95%CI) to achieve an ACR 20, 50, and 70 response were 2.46 (1.87-3.22), 4.37 (2.77-6.91), and 5.15 (2.60-10.22), with NNTs of 2.9, 3.1, and 5.3, respectively. At 52 weeks, adalimumab 40 mg e.o.w. and 20 mg every week (e.w.) significantly slowed the radiological progression including Sharp modified index, erosion score, and joint space score (only with 40 mg e.o.w.). In the comparison B, with adalimumab 40 mg e.o w. , the RRs to achieve an ACR 20, 50, and 70 response at 24/26 weeks were 1.91 (1.17-3.10), 2.84 (1.58-5.12), and 7.33 (2.25-33.90) with NNTs of 5.0 (95%CI 3.0-9.0), 7.0 (4.0-20.0), and 9.0 (3.0-38.0), respectively. In most of the analysed studies and comparisons, there were not significant differences in safety outcomes between adalimumab and control groups. The development of positive antinuclear antibodies was significantly more frequent in adalimumab patients than in placebo patients. Serious infections were significantly more frequent in adalimumab patients in only one study (Keystone 2004) with a RR (95%CI) of 7.64(1.02-57.18) and a NNH of 30.2. AUTHORS' CONCLUSIONS: On the basis of the studies reviewed here, adalimumab in combination with methotrexate is efficacious and safe in the treatment of the rheumatoid arthritis. Adalimumab 40 mg sc e.o.w. and 20 mg e.w. slows the radiographic progression at 52 weeks. Adalimumab in combination with DMARDs other than methotrexate is also efficacious and safe, even though data from one only study are available and the number of patients in each group is low. Adalimumab in monotherapy is efficacious and safe in the treatment of the rheumatoid arthritis but the effect size is lower than with combined therapy.

[Resource utilization in a cohort of rheumatoid arthritis patients attended in rheumatology units in Spain]. / Utilización de recursos en una cohorte de pacientes con artritis reumatoide atendidos en área especializada de reumatología en España.

OBJECTIVE: To determine resource use over a 1-year period in patients with rheumatoid arthritis (RA) attended in rheumatology units in hospitals within the Spanish public health system. PATIENTS AND METHODS: An observational, longitudinal, prospective, multicenter, 1-year study was performed in randomly selected rheumatology units in hospitals of the Spanish public health system. Patients with RA were randomly selected in each hospital. Four visits (at baseline and every 4 months) were conducted by a rheumatologist not routinely involved in the care of the patient. Demographic and disease-related variables were collected. Patient diaries and systematic interviews were used to gather data on resource use. RESULTS: A total of 301 patients were included and 190 (83% females) completed the study. The mean age was 59 ± 13 years and the mean disease duration was 10 ± 10 years. The resources most heavily used were medical. All of the patients made medical visits with a median of four visits to rheumatologists (1-13). Ninetynine percent of the patients took at least one drug. The most frequent drugs were paracetamol (41%), deflaza-cort (32%), and methotrexate (24%). Laboratory tests were performed in all patients, and x-rays were performed in 59%. Sixty-one patients (32%) were hospitalized; 75% of these patients were non-surgical. The most frequently used non-medical direct resources were meals and home visits by non-medical staff (39%). Thirtyone patients (16%) had some type of work disability. CONCLUSIONS: AR is associated with substantial utilization of medical and non-medical resources related to the disease and work disability.

[Cost analysis in a cohort of rheumatoid arthritis patients managed in rheumatology units in Spain]. / Análisis de costes en una cohorte de enfermos con artritis reumatoide atendidos en área especializada de reumatología en España.

OBJECTIVE: To assess the annual costs of rheumatoid arthritis (RA) patients attended at rheumatology units in Spanish public hospitals. METHODS: A longitudinal, prospective, multicenter, observational, 1-year study was performed in the rheumatology units of randomly selected Spanish public hospitals. Randomly selected RA patients were included. The patients made four visits (at baseline and every 4 months). Resource use and costs were collected from patient diaries and structured questionnaires. RESULTS: A total of 301 patients were included and 190 (83% women) completed the study. The mean (± SD) age was 59±13 years and the mean disease duration was 10±10 years. The median annual cost per patient was 3,845 euros (318-36,783). The estimated total annual cost of the Spanish RA population managed in the rheumatology units of public hospitals was 590,110,000 euros. Of total costs, 74% were direct costs and 26% were indirect costs. Medical costs represented 81% of direct costs. The main components of medical costs were drugs (56%), medical visits (21%), complementary tests (12%), and hospitalizations (11%). Permanent work disability represented 66% of indirect costs. CONCLUSIONS: Direct costs were substantially higher than indirect costs. The main components of medical costs were drugs. There was high variability in resource use with a wide range of annual costs per patient.

[Rofecoxib versus non-steroidal anti-inflammatory drugs in arthrosis treatment: cost-effectiveness analysis for Spain]. / Rofecoxib frente a antiinflamatorios no esteroideos en el tratamiento de la artrosis: análisis coste-efectividad para España.

OBJECTIVE: Analyze the efficiency of non-selective non-steroidal anti-inflammatory drugs (NSAIDs) versus rofecoxib prescription for arthrosis treatment in Spain through a theoretical model of cost-effectiveness. METHODOLOGY: A theoretical model of decision that evaluates the efficiency of the use of non-selective NSAIDs and rofecoxib in the treatment of patients > 65 years with arthrosis who were nonrespondent to the administration of acetaminophen 4 g/day. The analysis focuses on the estimate of the impact derived from the gastrointestinal (GI) adverse effects. Two alternative analysis contexts are considered: "customary clinical practice" and "rational use of GI drugs" with possible preventive use of gastroprotective (GP) drugs in both groups. The time horizon is 1 year. Direct expenses are estimated from the Spanish Health System perspective. The effectiveness parameter used is the number of severe GI complications prevented. RESULTS: Under the assumptions of the first context, with a 55% estimated combinated prescription of non-selective GP with NSAID, and 6% with rofecoxib, the percentage of cost compensation of rofecoxib is 72%. Under the assumptions of the second context, the cost of rofecoxib is totally compensated when the percentage of combinated prescription of GP with NSAIDs is 59%. CONCLUSION: The use of rofecoxib can be a cost-effective alternative with regard to the traditional non-selective NSAID in the arthrosis treatment, especially in context of higher preventive use of CI drugs.

La versión española del BASDAI es fiable y se correlaciona con la actividad de la enfermedad en pacientes con espondilitis anquilosante / The Spanish version of the BASDAI is reliable and correlates with disease activity in patients with ankylosing spondylitis

Objetivo: Estudiar la fiabilidad, validez de constructo y factibilidad de una versión en español del Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) para medir la actividad de la enfermedad en pacientes con espondilitis anquilosante (EA).Métodos: Estudio transversal. Se incluyeron pacientes con EA (criterios de Nueva York modificados). El mismo reumatólogo evaluó a todos los pacientes. Se registraron variables demográficas y relacionadas con la EA, incluyendo valoraciones globales del médico y el paciente, valoración del dolor por el paciente, BASDAI, BASFI (Bath Ankylosing Spondylitis Functional Index), BASMI (Bath Ankylosing Spondylitis Metrology Index) y cuestionarios de calidad de vida SF-36 y EuroQol. El BASDAI fue adaptado al español. Se estudiaron la fiabilidad (consistencia interna y reproducibilidad test-retest), validez de constructo y factibilidad (tiempo empleado y comprensión).Resultados: Se incluyeron 92 pacientes, 69 varones (75 por ciento), con edad (X +/- DE [media +/- desviación estándar]) de 40,7 +/- 9,1 años y duración de la enfermedad (X +/- DE) de 11 +/- 7,8 años. La puntuación del BASDAI mostró correlación estadísticamente significativa con r de Pearson mayores de 0,6 con a valoración del dolor por el paciente (VGP), valoración del dolor por el paciente y medido por el SF-36, función física medida por el BASFI y por el SF-36, calidad de vida medida por el SF-36 y Euro Qol y vitalidad medida por el SF-36. VGP, valoración del dolor por el paciente, BASFI y vitalidad mantuvieron asociación independiente con el BASDAI, en el modelo de regresión y explicaron el 73 por ciento de las variaciones en su puntuación. El coeficiente alfa de Cronbach fue de 0,87 y la prueba test-retest tuvo una rho de Spearman de 0,92, p<0,0001. El tiempo promedio fue de 60 segundos y la comprensión buena. Conclusiones: La versión en español del BASDAI mostró fiabilidad, validez de constructo y factibilidad, por lo que puede ser utilizada para medir la actividad de la enfermedad en pacientes españoles con EA (AU)

Costes calidad de vida-artritis reumatoide. Estudio económico y de la calidad de vida de los pacientes con artritis reumatoide en España. Resultados preliminares / The costs and quality of life in rheumatoid arthritis study in Spain. Preliminary results

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