Sarcopenia, immune-mediated rheumatic diseases, and nutritional interventions

Introduction: Sarcopenia is defined by a loss of muscle mass and function associated with mortality, decreased physical performance, falls, and disability. Since chronic inflammation and decreased physical activity are risk factors for developing sarcopenia, it is critical to assess the role of sarcopenia in immune-mediated rheumatic diseases (IMRDs). Moreover, nutritional interventions are emerging as key modifiable and affordable options to improve physical performance in sarcopenia. Objective: The aim of this review is to critically summarize current information on the evidence linking nutritional interventions and sarcopenia in IMRDs. Methods: The search and selection of articles was performed in Medline, Dimensions.ai, Google Scholar, Cochrane Library, Epistemonikos, and Trip Database. The results were clustered into three areas: sarcopenia and IMRDs, sarcopenia and biological disease-modifying antirheumatic drugs (bDMARDs), and nutritional interventions for sarcopenia. Findings: Several cross-sectional studies have shown a higher prevalence of sarcopenia in IMRDs, such as rheumatoid arthritis. Although not fully established, evidence linking sarcopenia and other IMRDs (ankylosing spondylitis and systemic sclerosis) has been also described. For secondary sarcopenia prevention and treatment, bDMARDs' administration proved efficacy in patients with rheumatoid arthritis. Furthermore, there is growing evidence linking nutrition to the prevention and treatment of sarcopenia. Evidence linking unfavourable results in nutritional risk assessment, insufficient intake of protein, vitamin D, antioxidant nutrients, and long-chain polyunsaturated fatty acids and sarcopenia have been reported. Conclusion: Given that sarcopenia and IMRDs have strong links, further research is needed to improve patient care

Lipoprotein(A) Concentrations In Rheumatoid Arthritis On Biologic Therapy: Results From The Cardiovascular In Rheumatology [Carma] Study Project

Background Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. Objective The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. Methods Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. Results Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (?: ?0.303, 95% confidence interval: ?0.558 to ?0.047; P = .02). Conclusions RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.This project has been supported by an unrestricted grant from Abbvie, Spain. The design, analysis, interpretation of results, and preparation of the article have been done independently of Abbvie. Dr González-Gay's studies have been supported by grants from “Fondo de Investigaciones Sanitarias” PI06/0024, PS09/00748, and PI12/00060 and RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain)

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Relación entre los polimorfismos genéticos relacionados con el transporte celular, poliglutamación y metabolismo de metotrexato y la respuesta terapéutica en artritis reumatoide

Metotrexato (MTX) es el tratamiento de primera elección en artritis reumatoide (AR). Existe enorme variabilidad en la respuesta terapéutica. Realizamos un estudio en una cohorte de 301 pacientes con AR tratados con MTX en monoterapia con el objetivo de conocer la influencia de las características clínicas y diferentes polimorfismos relacionados con el transporte y vías metabólicas del MTX sobre la respuesta terapéutica. Las variables de desenlace fueron la respuesta (baja actividad y remisión medidas por DAS28PCR) y la toxicidad por MTX. Se estudiaron los SNPs ABCB1_C3435T, GGH_T16C, FPG_G2782A, MTHFR_C677T, MTHFR_A1298C, AMPD1_C34T, ADA_A534G e ITPA_C94A, y variables relacionadas con el paciente, la enfermedad y el tratamiento. En una cohorte representativa de una AR grave, la mitad de los pacientes, especialmente mujeres, fumadores y con mayor gravedad basal, no alcanzaron una respuesta suficiente con la monoterapia. Se registraron acontecimientos adversos, principalmente gastrointestinales, neurológicos y hepáticos, en 50% de los pacientes, que motivaron la suspensión de MTX en 18% del total. La toxicidad se asoció a mujeres, menor edad y comorbilidad. La mayoría de los SNPs estudiados se ha asociado con alguna medida de desenlace, destacando la asociación de MTHFR_1298ACc con pobre respuesta y MTHFR_677TCc con buena respuesta. Algunos SNPs mostraron un efecto protector para la toxicidad, pero se asociaron con frecuencia a toxicidad global (MTHFR_677CTc, GGH_16TCc) y hepática (MTHFR_1298ACc, ADA_534AGc), especialmente en hombres. Los estudios de asociación genética deben tener en cuenta el sexo de los pacientes y otras variables clínicas. El tabaco es el principal factor modificable de respuesta a MTX.Methotrexate (MTX) is the first-choice treatment in rheumatoid arthritis (RA). There is a high variability in the therapeutic response. We conducted a case-control study nested in a cohort of 301 RA patients treated with MTX in monotherapy with the aim to explore the influence of clinical characteristics and different polymorphisms related to transport and metabolic pathways of MTX on the therapeutic response. The outcome variables were the response (low activity and remission measured by DAS28PCR) and MTX toxicity. We studied the SNPs ABCB1_C3435T, GGH_T16C, FPG_G2782A, MTHFR_C677T, MTHFR_A1298C, AMPD1_C34T, ADA_A534G and ITPA_C94A, and variables related to the patient, the disease and the treatment. In a cohort representative of severe RA, half of the patients, especially women, smokers and with more baseline severity, did not reach a sufficient response with monotherapy. Adverse events, gastrointestinal, neurological and hepatic mainly, were recorded in 50% of patients, which caused the suspension of MTX in an 18% of the total. Toxicity was associated to women, younger age and comorbidity. Most of the SNPs studied have been associated with some outcome measure, highlighting the association of MTHFR_1298ACc with poor response and MTHFR_677TCc with good response. Some SNPs showed a protective effect for toxicity, but, in general, they were frequently associated with global (MTHFR_677CTc, GGH_16TCc) and hepatic (MTHFR_1298ACc, ADA_534AGc) toxicity, especially in men. Genetic association studies should take into account the sex of patients and other clinical variables. Smoking is the main modifiable risk factor of MTX response

Relación entre los polimorfismos genéticos relacionados con el transporte celular, poliglutamación y metabolismo de metotrexato y la respuesta terapéutica en artritis reumatoide

Metotrexato (MTX) es el tratamiento de primera elección en artritis reumatoide (AR). Existe enorme variabilidad en la respuesta terapéutica. Realizamos un estudio en una cohorte de 301 pacientes con AR tratados con MTX en monoterapia con el objetivo de conocer la influencia de las características clínicas y diferentes polimorfismos relacionados con el transporte y vías metabólicas del MTX sobre la respuesta terapéutica. Las variables de desenlace fueron la respuesta (baja actividad y remisión medidas por DAS28PCR) y la toxicidad por MTX. Se estudiaron los SNPs ABCB1_C3435T, GGH_T16C, FPG_G2782A, MTHFR_C677T, MTHFR_A1298C, AMPD1_C34T, ADA_A534G e ITPA_C94A, y variables relacionadas con el paciente, la enfermedad y el tratamiento. En una cohorte representativa de una AR grave, la mitad de los pacientes, especialmente mujeres, fumadores y con mayor gravedad basal, no alcanzaron una respuesta suficiente con la monoterapia. Se registraron acontecimientos adversos, principalmente gastrointestinales, neurológicos y hepáticos, en 50% de los pacientes, que motivaron la suspensión de MTX en 18% del total. La toxicidad se asoció a mujeres, menor edad y comorbilidad. La mayoría de los SNPs estudiados se ha asociado con alguna medida de desenlace, destacando la asociación de MTHFR_1298ACc con pobre respuesta y MTHFR_677TCc con buena respuesta. Algunos SNPs mostraron un efecto protector para la toxicidad, pero se asociaron con frecuencia a toxicidad global (MTHFR_677CTc, GGH_16TCc) y hepática (MTHFR_1298ACc, ADA_534AGc), especialmente en hombres. Los estudios de asociación genética deben tener en cuenta el sexo de los pacientes y otras variables clínicas. El tabaco es el principal factor modificable de respuesta a MTX.Methotrexate (MTX) is the first-choice treatment in rheumatoid arthritis (RA). There is a high variability in the therapeutic response. We conducted a case-control study nested in a cohort of 301 RA patients treated with MTX in monotherapy with the aim to explore the influence of clinical characteristics and different polymorphisms related to transport and metabolic pathways of MTX on the therapeutic response. The outcome variables were the response (low activity and remission measured by DAS28PCR) and MTX toxicity. We studied the SNPs ABCB1_C3435T, GGH_T16C, FPG_G2782A, MTHFR_C677T, MTHFR_A1298C, AMPD1_C34T, ADA_A534G and ITPA_C94A, and variables related to the patient, the disease and the treatment. In a cohort representative of severe RA, half of the patients, especially women, smokers and with more baseline severity, did not reach a sufficient response with monotherapy. Adverse events, gastrointestinal, neurological and hepatic mainly, were recorded in 50% of patients, which caused the suspension of MTX in an 18% of the total. Toxicity was associated to women, younger age and comorbidity. Most of the SNPs studied have been associated with some outcome measure, highlighting the association of MTHFR_1298ACc with poor response and MTHFR_677TCc with good response. Some SNPs showed a protective effect for toxicity, but, in general, they were frequently associated with global (MTHFR_677CTc, GGH_16TCc) and hepatic (MTHFR_1298ACc, ADA_534AGc) toxicity, especially in men. Genetic association studies should take into account the sex of patients and other clinical variables. Smoking is the main modifiable risk factor of MTX response

Biologic Disease-modifying antirheumatic drug attributes in the first lines of treatment of rheumatoid arthritis. 2015 ACORDAR project

Existen pacientes con artritis reumatoide (AR) que no responden de la forma deseada a la terapia biológica. Nuestro objetivo fue reconocer los atributos del FAME biológico (FAMEb) que podrían identificar al más adecuado en las primeras líneas de tratamiento de la AR. Métodos Para reconocer los atributos que podrían definir el FAMEb, se realizó una búsqueda sistemática de la literatura acerca de aspectos generales, farmacología, eficacia, seguridad, administración y coste. A continuación, se realizó un proceso Delphi a 2 rondas entre un grupo de reumatólogos expertos en el manejo de la AR para determinar el grado de acuerdo con los atributos identificados, indicando el grado de importancia que se le daba a cada atributo. Se aplicaron 2 criterios para determinar la consistencia de los resultados: 1) sobre la base de la mediana y el rango intercuartílico, y 2) el cumplimiento simultáneo de media, mediana, desviación estándar, rango intercuartílico y coeficiente de variación. Se determinaron también la concordancia y la ratificación final del panel de expertos. Resultados Ochenta y tres reumatólogos españoles completaron las 2 circulaciones del proceso Delphi. Ninguno de los 77 atributos identificados se consideró de baja importancia, 75 de los 77 (97,4%) se consideraron de alta importancia y 76 de los 77 (98,7%) fueron ratificados. Quince tuvieron el apoyo del 100% del grupo de trabajo. Conclusiones Quince atributos tuvieron el apoyo del 100% del grupo de trabajo y podrían considerarse los que definirían el FAMEb ideal en las primeras líneas de tratamiento de la AR.To date, between 17% and 35% of patients with rheumatoid arthritis (RA) do not respond as expected to the initial biological therapy. The objective of this project is to recognize and weigh the attributes of biologic DMARD (bDMARD) to identify the most appropriate for each case, in the first lines of treatment of RA (after inadequate response to at least one synthetic DMARD or previous bDMARD). Methods To recognize the possible attributes that could define the bDMARD, we performed a systematic search of the literature that recognized the possible attributes involving general aspects, pharmacology, efficacy, safety, management, and cost. Then a Delphi process was conducted with two rounds among a group of selected expert rheumatologists in the management of RA indicating the degree of agreement with the attributes identified in the literature. The project was completed between February and September 2015, indicating the degree of importance that was ascribed to each attribute. Two criteria were applied to determine the consistency of results: 1) based on the median and interquartile range; and 2) on the simultaneous compliance with mean, median, standard deviation, interquartile range and coefficient of variation. The agreement and final ratification of the expert panel were also determined. Results Eighty-three Spanish rheumatologists participated and completed both rounds of the Delphi process. In no case was the importance of the 77 attributes identified considered to be low; 75 of 77 (97.4%) were considered highly important and 76 of 77 (98.7%) were ratified. Fifteen attributes had the support of 100% of the working group. Conclusions There was a high degree of agreement concerning the selected attributes. Fifteen of them had the support of 100% of the working group and could be considered the definition of the ideal bDMARD in the first lines of RA treatment.Sin financiaciónNo data JCR 20180.363 SJR (2018) Q3, 38/66 RheumatologyNo data IDR 2018UE

KEEPUPMCIVIL: a global online course for first year students in engineering and architecture degrees

During the last decades, the advance of technology has produced substantial changes in teaching and learning methodologies. In this context, we present KEEPUPMCIVIL, an online course for first year students, conducted through the Educational Innovation Project of the Universidad Politécnica de Madrid (PI-1819-5801). The online course includes, in a global virtual space, the first year subjects within Civil Engineering Degree at the Universidad Politécnica de Madrid. The institutional Moodle platform provided by the Universidad Politécnica de Madrid, can or cannot be used by each teacher, who is free to decide to host his subject within the platform, although this practice is hardly recommended. When implemented in Moodle, the individual courses do not interact between each other. The proposed global course presents an innovative format where a global visión of the first year course is developed. The main objective of KEEPUPMCIVIL is to supply the students with different resources that promote autonomous learning, thus the students themselves manage their individual learning, although encouraging collaborative work through forums and team activities available in each subject. Through these forums, students can get in touch with each other, exchange opinions, answer questions and advance in learning, even if they do not have a teacher available. This strategy will be very useful for students who are not able to attend normal classes for several reasons. The professors, who normally conduct the subjects, use their own methodologies to implement and design their individual virtual course. Therefore, different materials are included: notes, presentations, videos, computer programs, questionnaires, etc., making sure that the most suitable resources are considered to easy individual learning and acquisition of competences related to the different subjects. Despite this freedom when choosing the resources to be used in each subject, KEEPUPMCIVIL global course has been designed to display an attractive common layout that is user-friendly for both students and teachers. In fact, some professors of final year subjects have expressed interest in applying the same strategies. The subjects included in the course are: - Linear Algebra and Geometry – Calculus - Statistics and Numerical Analysis - Applied Computing - Chemistry of Materials – Physics – Geology - Drawing and Representation Systems - Management and Business Administration - Technical Mechanics. Each subject begins with a representative image and an introduction of interest, in order to highlight the need to acquire solid scientific foundation as well as specific knowledge of the degree. Since KEEPUPMCIVIL begins the 2019-20 academic year, the professors responsible for each subject will monitor the functioning and resources use by measuring the access volume and other analytics. The potential of internal transfer of this global course within the UPM is clear, since the first-year subjects of several engineering degree programs within the UPM are similar. In addition, at the external level, the possibility of implementing a MOOC (Masive Open Online Course ) based on this global course is also considered

Higher prevalence of psoriatic arthritis in the adult population in Spain? A population-based cross-sectional study.

ObjectiveThe prevalence of psoriatic arthritis (PsA) is very heterogeneous. There are no data on its frequency in the general population in Spain. The aim of EPISER2016 study was to estimate the prevalence of PsA in people aged ≥20 years in Spain.MethodsCross-sectional multicenter population-based study. Subjects from all the autonomous communities in Spain were randomly selected using multistage stratified cluster sampling. Participants in each of the municipalities randomly selected for the study were administered a telephone-based questionnaire to screen for the study diseases. If the participant reported being previously diagnosed, rheumatologists from the participant's reference hospital confirmed the diagnosis based on a review of the clinical history. Subjects not previously diagnosed but whose screening result was positive based on symptoms received a second telephone call from the investigating rheumatologist in order to evaluate the suspicion. If the suspicion remained, an appointment was made at the reference hospital to complete the diagnostic confirmation process according to CASPAR criteria. To calculate the prevalence and its 95% confidence interval (CI), the sample design was taken into account and weighing was calculated considering age, sex and geographic origin.ResultsThe sample comprised 4916 subjects. The prevalence of PsA was 0.58% (95%CI: 0.38-0.87). All but 1 of the 27 cases (96.30%) had been diagnosed prior to EPISER2016.ConclusionThe prevalence of PsA in Spain was among the highest reported to date, only below that reported in Norway (0.67%) and slightly higher than that reported in Italy (0.42%)