Exploring EEG-based motor imagery decoding: a dual approach using spatial features and spectro-spatial Deep Learning model IFNet.

Introduction: In recent years, the decoding of motor imagery (MI) from electroencephalography (EEG) signals has become a focus of research for brain-machine interfaces (BMIs) and neurorehabilitation. However, EEG signals present challenges due to their non-stationarity and the substantial presence of noise commonly found in recordings, making it difficult to design highly effective decoding algorithms. These algorithms are vital for controlling devices in neurorehabilitation tasks, as they activate the patient's motor cortex and contribute to their recovery. Methods: This study proposes a novel approach for decoding MI during pedalling tasks using EEG signals. A widespread approach is based on feature extraction using Common Spatial Patterns (CSP) followed by a linear discriminant analysis (LDA) as a classifier. The first approach covered in this work aims to investigate the efficacy of a task-discriminative feature extraction method based on CSP filter and LDA classifier. Additionally, the second alternative hypothesis explores the potential of a spectro-spatial Convolutional Neural Network (CNN) to further enhance the performance of the first approach. The proposed CNN architecture combines a preprocessing pipeline based on filter banks in the frequency domain with a convolutional neural network for spectro-temporal and spectro-spatial feature extraction. Results and discussion: To evaluate the approaches and their advantages and disadvantages, EEG data has been recorded from several able-bodied users while pedalling in a cycle ergometer in order to train motor imagery decoding models. The results show levels of accuracy up to 80% in some cases. The CNN approach shows greater accuracy despite higher instability.

Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes.

BACKGROUND: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. RESULTS: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. CONCLUSIONS: Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.

Magnetoinductive metasurface of capacitively-loaded split rings for local field homogenization in a 7 T MRI birdcage: A simulation study.

The transmit field B1+ in a 7 T birdcage is inherently inhomogeneous due to the effects of wavelengths on tissue. This work investigates the homogenization of this field through metasurfaces that consist of a two-dimensional planar array of capacitively loaded conducting rings. The metasurfaces are placed in the intermediate space between the head and the birdcage on either side of the head. The periodical structure of this type of metasurface supports magnetoinductive waves because of the mutual inductive coupling existing between the elements of the array. The analysis takes advantage of this coupling and exploits the excitation of a standing magnetoinductive wave across the arrays, which creates a strong local field that contributes to locally homogenize the field of the birdcage. The presence of the arrays does not detune the birdcage, so that they can be used with commercial birdcages that operate both to transmit and to receive.

The complex landscape of TMS devices: A brief overview.

The increasing application of TMS in research and therapy has spawned an ever-growing number of commercial and non-commercial TMS devices and technology development. New CE-marked devices appear at a rate of approximately one every two years, with new FDA-approved application of TMS occurring at a similar rate. With the resulting complex landscape of TMS devices and their application, accessible information about the technological characteristics of the TMS devices, such as the type of their circuitry, their pulse characteristics, or permitted protocols would be beneficial. We here present an overview and open access database summarizing key features and applications of available commercial and non-commercial TMS devices (http://www.tmsbase.info). This may guide comparison and decision making about the use of these devices. A bibliometric analysis was performed by identifying commercial and non-commercial TMS devices from which a comprehensive database was created summarizing their publicly available characteristics, both from a technical and clinical point of view. In this document, we introduce both the commercial devices and prototypes found in the literature. The technical specifications that unify these devices are briefly analysed in two separate tables: power electronics, waveform, protocols, and coil types. In the prototype TMS systems, the proposed innovations are focused on improving the treatment regarding the patient: noise cancellation, controllable parameters, and multiple stimulation. This analysis shows that the landscape of TMS is becoming increasingly fragmented, with new devices appearing ever more frequently. The review provided here can support development of benchmarking frameworks and comparison between TMS systems, inform the choice of TMS platforms for specific research and therapeutic applications, and guide future technology development for neuromodulation devices. This standardisation strategy will allow a better end-user choice, with an impact on the TMS manufacturing industry and a homogenisation of patient samples in multi-centre clinical studies. As an open access repository, we envisage the database to grow along with the dynamic development of TMS devices and applications through community-lead curation.

Spasticity evaluation with the Amadeo Tyromotion device in patients with hemispheric stroke.

Objective: The objective of this study is to verify the reliability and the concurrent and discriminant validity of the measurements of spasticity offered by the robotic device, quantifying the (1) test-retest reliability, (2) correlation with the clinical evaluation using the Modified Ashworth Scale (MAS), (3) inter-rater reliability between the two physiotherapists, and (4) ability to discriminate between healthy and stroke patients. Methods: A total of 20 stroke patients and 20 healthy volunteers participated in the study. Two physical therapists (PT1 and PT2) independently evaluated the hand spasticity of stroke subjects using the MAS. Spasticity was assessed, both in healthy and stroke patients, with the Amadeo device at three increasing velocities of passive movement for three consecutive repeated assessments, while raw data of force and position were collected through an external program. Data analysis: The intraclass correlation coefficient (ICC) and the weighted kappa were computed to estimate the reliability of the Amadeo device measurements, the inter-rater reliability of MAS, and the correlation between the MAS and Amadeo device measurements. The discriminant ability of the Amadeo device was assessed by comparing the stroke and healthy subjects' spasticity measurements with the percentage of agreements with 0 in MAS for healthy subjects. Results: The test-retest reliability of the Amadeo device was high with ICC at all three velocities (ICC = 0.908, 0.958, and 0.964, respectively) but lower if analyzed with weighted kappa correlation (0.584, 0.748, and 0.749, respectively) as mean values for each velocity. The correlation between Amadeo and the clinical scale for stroke patients with weighted kappa correlation was poor (0.280 ± 0.212 for PT1 and 0.290 ± 0.155 for PT2). The inter-rater reliability of the clinical MAS was high (ICC = 0.911). Conclusion: Both MAS and Amadeo spasticity scores showed good reliability. The Amadeo scores did not show a strong clinical correlation with the MAS in stroke patients. Hitherto, Amadeo evaluation shows trends that are consistent with the characteristics of spasticity, such as an increase in spasticity as the speed of muscle stretching increases. The ability of the device to discriminate between stroke patients and healthy controls is low. Future studies adopting an instrumental gold standard for spasticity may provide further insight into the validity of these measurements.

An EEG database for the cognitive assessment of motor imagery during walking with a lower-limb exoskeleton.

One important point in the development of a brain-machine Interface (BMI) commanding an exoskeleton is the assessment of the cognitive engagement of the subject during the motor imagery tasks conducted. However, there are not many databases that provide electroencephalography (EEG) data during the use of a lower-limb exoskeleton. The current paper presents a database designed with an experimental protocol aiming to assess not only motor imagery during the control of the device, but also the attention to gait on flat and inclined surfaces. The research was conducted as an EUROBENCH subproject in the facilities sited in Hospital Los Madroños, Brunete (Madrid). The data validation reaches accuracies over 70% in the assessment of motor imagery and attention to gait, which marks the present database as a valuable resource for researches interested on developing and testing new EEG-based BMIs.

Making Bipedal Robot Experiments Reproducible and Comparable: The Eurobench Software Approach.

This study describes the software methodology designed for systematic benchmarking of bipedal systems through the computation of performance indicators from data collected during an experimentation stage. Under the umbrella of the European project Eurobench, we collected approximately 30 protocols with related testbeds and scoring algorithms, aiming at characterizing the performances of humanoids, exoskeletons, and/or prosthesis under different conditions. The main challenge addressed in this study concerns the standardization of the scoring process to permit a systematic benchmark of the experiments. The complexity of this process is mainly due to the lack of consistency in how to store and organize experimental data, how to define the input and output of benchmarking algorithms, and how to implement these algorithms. We propose a simple but efficient methodology for preparing scoring algorithms, to ensure reproducibility and replicability of results. This methodology mainly constrains the interface of the software and enables the engineer to develop his/her metric in his/her favorite language. Continuous integration and deployment tools are then used to verify the replicability of the software and to generate an executable instance independent of the language through dockerization. This article presents this methodology and points at all the metrics and documentation repositories designed with this policy in Eurobench. Applying this approach to other protocols and metrics would ease the reproduction, replication, and comparison of experiments.

Legged locomotion over irregular terrains: state of the art of human and robot performance.

Legged robotic technologies have moved out of the lab to operate in real environments, characterized by a wide variety of unpredictable irregularities and disturbances, all this in close proximity with humans. Demonstrating the ability of current robots to move robustly and reliably in these conditions is becoming essential to prove their safe operation. Here, we report an in-depth literature review aimed at verifying the existence of common or agreed protocols and metrics to test the performance of legged system in realistic environments. We primarily focused on three types of robotic technologies, i.e., hexapods, quadrupeds and bipeds. We also included a comprehensive overview on human locomotion studies, being it often considered the gold standard for performance, and one of the most important sources of bioinspiration for legged machines. We discovered that very few papers have rigorously studied robotic locomotion under irregular terrain conditions. On the contrary, numerous studies have addressed this problem on human gait, being nonetheless of highly heterogeneous nature in terms of experimental design. This lack of agreed methodology makes it challenging for the community to properly assess, compare and predict the performance of existing legged systems in real environments. On the one hand, this work provides a library of methods, metrics and experimental protocols, with a critical analysis on the limitations of the current approaches and future promising directions. On the other hand, it demonstrates the existence of an important lack of benchmarks in the literature, and the possibility of bridging different disciplines, e.g., the human and robotic, towards the definition of standardized procedures that will boost not only the scientific development of better bioinspired solutions, but also their market uptake.

A unified scheme for the benchmarking of upper limb functions in neurological disorders.

BACKGROUND: In neurorehabilitation, we are witnessing a growing awareness of the importance of standardized quantitative assessment of limb functions. Detailed assessments of the sensorimotor deficits following neurological disorders are crucial. So far, this assessment has relied mainly on clinical scales, which showed several drawbacks. Different technologies could provide more objective and repeatable measurements. However, the current literature lacks practical guidelines for this purpose. Nowadays, the integration of available metrics, protocols, and algorithms into one harmonized benchmarking ecosystem for clinical and research practice is necessary. METHODS: This work presents a benchmarking framework for upper limb capacity. The scheme resulted from a multidisciplinary and iterative discussion among several partners with previous experience in benchmarking methodology, robotics, and clinical neurorehabilitation. We merged previous knowledge in benchmarking methodologies for human locomotion and direct clinical and engineering experience in upper limb rehabilitation. The scheme was designed to enable an instrumented evaluation of arm capacity and to assess the effectiveness of rehabilitative interventions with high reproducibility and resolution. It includes four elements: (1) a taxonomy for motor skills and abilities, (2) a list of performance indicators, (3) a list of required sensor modalities, and (4) a set of reproducible experimental protocols. RESULTS: We proposed six motor primitives as building blocks of most upper-limb daily-life activities and combined them into a set of functional motor skills. We identified the main aspects to be considered during clinical evaluation, and grouped them into ten motor abilities categories. For each ability, we proposed a set of performance indicators to quantify the proposed ability on a quantitative and high-resolution scale. Finally, we defined the procedures to be followed to perform the benchmarking assessment in a reproducible and reliable way, including the definition of the kinematic models and the target muscles. CONCLUSIONS: This work represents the first unified scheme for the benchmarking of upper limb capacity. To reach a consensus, this scheme should be validated with real experiments across clinical conditions and motor skills. This validation phase is expected to create a shared database of human performance, necessary to have realistic comparisons of treatments and drive the development of new personalized technologies.

Static magnetic field stimulation over motor cortex modulates resting functional connectivity in humans.

Focal application of transcranial static magnetic field stimulation (tSMS) over the human motor cortex induces local changes in cortical excitability. Whether tSMS can also induce distant network effects, and how these local and distant effects may vary over time, is currently unknown. In this study, we applied 10 min tSMS over the left motor cortex of healthy subjects using a real/sham parallel design. To measure tSMS effects at the sensori-motor network level, we used resting-state fMRI. Real tSMS, but not sham, reduced functional connectivity within the stimulated sensori-motor network. This effect of tSMS showed time-dependency, returning to sham levels after the first 5 min of fMRI scanning. With 10 min real tSMS over the motor cortex we did not observe effects in other functional networks examined (default mode and visual system networks). In conclusion, 10 min of tSMS over a location within the sensori-motor network reduces functional connectivity within the same functional network.

Dietary habits in patients with fibromyalgia: a cross-sectional study.

OBJECTIVES: To the scarce information on dietary habits in fibromyalgia (FM), it is added that there are no comparative studies with other rheumatic diseases. The objective of this study was to characterise the dietary habits of patients with FM by comparing, for the first time, with healthy controls (HC) and rheumatoid arthritis (RA). METHODS: This cross-sectional, observational study was based on data obtained from the Dietfibrom project for FM and from the IMID Consortium for RA and HC. All participants completed a food frequency questionnaire evaluating their weekly dietary intake of main food groups. The three cohorts were compared using a multiple logistic regression model adjusted for age, sex, and body mass index. RESULTS: After quality control, n=287 FM, n=1,983 HC and n=1,942 RA patients were analysed. We found that FM had a profound impact in the diet compared to HC, reducing the consumption of dairy (OR=0.32, p<0.0001), bread and/or whole grain cereals (OR=0.59, p=0.0006), fresh fruit (OR=0.66, P=0.008), and fish (OR=0.64, p=0.002). These same four food groups were also significantly reduced in FM patients in comparison to RA patients (p<0.0005 in all cases). Additionally, a lower consumption of pasta, rice and/or potatoes was also observed in FM compared to RA (OR=0.72, p=0.028). CONCLUSIONS: The present cross-sectional study shows that FM is associated to a significant change in the normal dietary patterns. These results underscore the importance of diet in this prevalent disease and are a warning of the potential long-range effects of a deficient nutritional status.

Food groups associated with immune-mediated inflammatory diseases: a Mendelian randomization and disease severity study.

BACKGROUND/OBJECTIVES: Immune-mediated inflammatory diseases (IMIDs) are prevalent diseases. There is, however, a lack of understanding of the link between diet and IMIDs, how much dietary patterns vary between them and if there are food groups associated with a worsening of the disease. SUBJECTS/METHODS: To answer these questions we analyzed a nation-wide cohort of n = 11,308 patients from six prevalent IMIDs and 2050 healthy controls. We compared their weekly intake of the major food categories, and used a Mendelian randomization approach to determine which dietary changes are caused by disease. Within each IMID, we analyzed the association between food frequency and disease severity. RESULTS: After quality control, n = 11,230 recruited individuals were used in this study. We found that diet is profoundly altered in all IMIDs: at least three food categories are significantly altered in each disease (P < 0.05). Inflammatory bowel diseases showed the largest differences compared to controls (n ≥ 8 categories, P < 0.05). Mendelian randomization analysis supported that some of these dietary changes, like vegetable reduction in Crohn's Disease (P = 2.5 × 10-10, OR(95% CI) = 0.73(0.65, 0.80)), are caused by the disease. Except for Psoriatic Arthritis and Systemic Lupus Erythematosus, we have found ≥2 food groups significantly associated with disease severity in the other IMIDs (P < 0.05). CONCLUSIONS: This cross-disease study demonstrates that prevalent IMIDs are associated to a significant change in the normal dietary patterns. This variation is highly disease-specific and, in some cases, it is caused by the disease itself. Severity in IMIDs is also associated with specific food groups. The results of this study underscore the importance of studying diet in IMIDs.

Opioides en la artrosis / Opioids in osteoarthritis

La artrosis (OA) es una de las principales causas de discapacidad y dolor crónico. La OA es también responsable de un sustancial coste sociosanitario, tanto directo como por la pérdida de productividad laboral e invalidez. A pesar de numerosos esfuerzos, los tratamientos para mitigar el impacto de esta enfermedad no han alcanzado el umbral deseable de eficacia. Revisamos la utilidad de los opioides para la terapia del dolor de la OA. Los opioides proporcionan un alivio clínicamente poco relevante del dolor en el corto y medio plazo. Pueden mejorar la capacidad funcional a corto, pero no a medio plazo. La tolerabilidad a estos agentes es baja. Por lo tanto, los opioides juegan un papel limitado en el manejo del dolor por la OA en un reducido grupo de pacientes.(AU)

Osteoarthritis (OA) rank highly among global causes of disability and chronic pain. OA is also responsible for substantial health and societal costs, both directly and as a consequence of impaired work productivity and early retirement. Despite numerous efforts, treatments to paliate the impact of the disease have not reached a threshold of efficacy. We review the utility of opioids for the treatment of pain due to OA. Opioids provide no clinically relevant pain relief in the short- and intermediate-term for osteoarthritis pain. They provide a clinically relevant reduction in disability in the short but not in the intermediate term. The short- and intermediate-term tolerability of opioids is low. Therefore, opioids have a limited role in the management of OA pain in selected patients.(AU)

Prefiltering based on experimental paradigm for analysis of fMRI complex brain networks.

Brain networks offers a new insight about connections between function and anatomical regions of human brain. We present results from brain networks built from functional magnetic resonance images during finger tapping paradigm. Pearson voxel-voxel correlation in time and frequency domains were performed for all subjects. Besides this standard framework we have implemented a new approach consisting in filtering the data with respect to the fMRI paradigm (finger tapping) in order to obtain a better understanding of the network involved in the execution of the task. The main topological graph measures have been compared in both cases: voxel-voxel correlation and voxel-paradigm filtering plus voxel-voxel correlation. With the standard voxel-voxel correlation a clearly free-scale network was obtained. On the other hand, when we prefiltered the paradigm we obtained two different kind of networks: 1) free-scale; 2) random-like. To our best knowledge, this behaviour is reported here for first time for brain networks. We suggest that paradigm signal prefiltering can provide more infomation about the brain networks.

Aspectos prácticos de la medición de los niveles de fármacos biológicos y de anticuerpos antifármaco en artritis reumatoide y espondiloartritis / Practical aspects of biological throught levels and antidrug antibodies in rheumatoid arthritis and spondyloarthritis

OBJETIVOS: Emitir recomendaciones sobre aspectos prácticos de la monitorización de los niveles de fármacos biológicos que puedan ser de utilidad para reumatólogos. MÉTODOS: Se realizó una revisión sistemática de la literatura de estudios en los que se determinaron niveles de fármaco y de anticuerpos antifármaco en pacientes con artritis reumatoide o espondiloartritis para estudiar si podían predecir diferentes desenlaces. Con los resultados de la revisión un grupo de expertos discutió bajo qué circunstancias podría ser útil la solicitud de niveles de fármacos biológicos y sus anticuerpos, lo que se concretó en una serie de preguntas clínicas que fueron respondidas con la evidencia científica disponible y creándose algoritmos para facilitar la toma de decisiones. RESULTADOS: Se establece que la determinación de los niveles de fármaco puede ser especialmente útil en 2 situaciones clínicas, cuando hay fallo al tratamiento (primario o secundario) y en remisión mantenida. Se revisa también qué técnica de laboratorio y momento para tomar la muestra son los más adecuados para la medición, y se establecen recomendaciones sobre la interpretación de los niveles de fármaco y sobre factores a tener en cuenta (por ejemplo, índice de masa corporal y fármacos modificadores de la enfermedad). CONCLUSIONES: Se han elaborado algoritmos y establecido posibles pautas y directrices para solicitar niveles de fármaco y de anticuerpos antifármaco en pacientes con artritis reumatoide y espondiloartritis, basados en la evidencia, que pueden ayudar a la toma de decisiones clínicas

OBJECTIVES: Issue recommendations on practical aspects of the monitoring of levels of biological drugs that may be useful for rheumatologists. METHODS: We conducted a systematic review of studies in which drug and anti-drug antibody levels were determined in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) to study whether they could predict different outcomes. In light of the results of the review, a group of experts discussed under what circumstances testing biological drug levels and their antibodies could be useful. The discussion resulted in a series of clinical questions that were answered with the scientific evidence collected, and in algorithms that facilitate decision making. RESULTS: It was established that the determination of drug levels can be especially useful in two clinical situations, on treatment failure (primary or secondary) and on sustained remission. It is also reviewed which laboratory technique and timing for sample drawing are the most suitable for the measurement. Recommendations are issued on the interpretation of drug levels and on factors to be taken into account (for example, body mass index and disease modifying drugs). CONCLUSIONS: Evidence-based algorithms and guidelines have been established to test drug levels and anti-drug antibodies in patients with RA and SpA, which can help clinical decision making

Eficacia y seguridad de los glucocorticoides en la artritis reumatoide: revisión sistemática de la literatura / Efficacy and safety of glucocorticoids in rheumatoid arthritis: systematic literature review

OBJETIVOS: 1) Revisar sistemática y críticamente la evidencia sobre las características de uso, eficacia y seguridad de los glucocorticoides (GC) en la artritis reumatoide (AR); 2) emitir recomendaciones prácticas sobre su utilización. MÉTODOS: Se realizó una revisión sistemática de la literatura con una estrategia de búsqueda bibliográfica sensible en Medline, Embase y Cochrane Library. Se seleccionaron ensayos clínicos aleatorizados que analizasen la eficacia y/o la seguridad de los GC en pacientes con AR. Dos revisores realizaron la primera selección por título y abstract y 10, la selección tras lectura en detalle y la recogida de datos. La calidad se evaluó con la escala de Jadad. En una reunión de grupo nominal con base en sus resultados se consensuaron una serie de recomendaciones. RESULTADOS: Se incluyeron 47 artículos. Los GC, en combinación con los fármacos antirreumáticos modificadores de la enfermedad, ayudan a controlar la actividad de la enfermedad y a inhibir la progresión radiográfica, especialmente en el corto-medio plazo y en las AR de inicio. Los GC pueden mejorar la función y el dolor. Distintos tipos y vías de administración son eficaces, sin que exista un esquema de tratamiento estandarizado (dosis de inicio, desescalada y duración del tratamiento con los GC) superior a otro. Los acontecimientos adversos de los GC son muy frecuentes, dependientes de la dosis, de gravedad variable, muchos de ellos leves. Se generaron 7 recomendaciones sobre el uso y la gestión del riesgo de los GC. CONCLUSIONES: Estas recomendaciones pretenden resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones con respecto al uso de GC en la AR

OBJECTIVES: 1) To systematically and critically review the evidence on the characteristics, efficacy and safety of glucocorticoids (CS) in rheumatoid arthritis (RA); 2) to generate practical recommendations. METHODS: A systematic literature review was performed through a sensitive bibliographic search strategy in Medline, Embase and the Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of CS in patients with RA. Two reviewers performed the first selection by title and abstract. Then 10 reviewers selected the studies after a detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. In a nominal group meeting, based on the results of the systematic literature review, related recommendations were reached by consensus. RESULTS: A total of 47 articles were finally included. CS in combination with disease-modifying antirheumatic drugs help control disease activity and inhibit radiographic progression, especially in the short-to-medium term and in early RA. CS can also improve function and relieve pain. Different types and routes of administration are effective, but there is no standardized scheme (initial dose, tapering and duration of treatment) that is superior to others. Adverse events when using CS are very frequent and are dose-dependent and variable severity, although most are mild. Seven recommendations were generated on the use and risk management of CS. CONCLUSIONS: These recommendations aim to resolve some common clinical questions and aid in decision-making for CS use in RA

Practical Aspects of Biological Throught Levels and Antidrug Antibodies in Rheumatoid Arthritis and Spondyloarthritis. / Aspectos prácticos de la medición de los niveles de fármacos biológicos y de anticuerpos antifármaco en artritis reumatoide y espondiloartritis.

OBJECTIVES: Issue recommendations on practical aspects of the monitoring of levels of biological drugs that may be useful for rheumatologists. METHODS: We conducted a systematic review of studies in which drug and anti-drug antibody levels were determined in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA) to study whether they could predict different outcomes. In light of the results of the review, a group of experts discussed under what circumstances testing biological drug levels and their antibodies could be useful. The discussion resulted in a series of clinical questions that were answered with the scientific evidence collected, and in algorithms that facilitate decision making. RESULTS: It was established that the determination of drug levels can be especially useful in two clinical situations, on treatment failure (primary or secondary) and on sustained remission. It is also reviewed which laboratory technique and timing for sample drawing are the most suitable for the measurement. Recommendations are issued on the interpretation of drug levels and on factors to be taken into account (for example, body mass index and disease modifying drugs). CONCLUSIONS: Evidence-based algorithms and guidelines have been established to test drug levels and anti-drug antibodies in patients with RA and SpA, which can help clinical decision making.

Efficacy and safety of glucocorticoids in rheumatoid arthritis: Systematic literature review. / Eficacia y seguridad de los glucocorticoides en la artritis reumatoide: revisión sistemática de la literatura.

OBJECTIVES: 1) To systematically and critically review the evidence on the characteristics, efficacy and safety of glucocorticoids (CS) in rheumatoid arthritis (RA); 2) to generate practical recommendations. METHODS: A systematic literature review was performed through a sensitive bibliographic search strategy in Medline, Embase and the Cochrane Library. We selected randomized clinical trials that analyzed the efficacy and/or safety of CS in patients with RA. Two reviewers performed the first selection by title and abstract. Then 10 reviewers selected the studies after a detailed review of the articles and data collection. The quality of the studies was evaluated with the Jadad scale. In a nominal group meeting, based on the results of the systematic literature review, related recommendations were reached by consensus. RESULTS: A total of 47 articles were finally included. CS in combination with disease-modifying antirheumatic drugs help control disease activity and inhibit radiographic progression, especially in the short-to-medium term and in early RA. CS can also improve function and relieve pain. Different types and routes of administration are effective, but there is no standardized scheme (initial dose, tapering and duration of treatment) that is superior to others. Adverse events when using CS are very frequent and are dose-dependent and variable severity, although most are mild. Seven recommendations were generated on the use and risk management of CS. CONCLUSIONS: These recommendations aim to resolve some common clinical questions and aid in decision-making for CS use in RA.

A Combined Transcriptomic and Genomic Analysis Identifies a Gene Signature Associated With the Response to Anti-TNF Therapy in Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is the most frequent autoimmune disease involving the joints. Although anti-TNF therapies have proven effective in the management of RA, approximately one third of patients do not show a significant clinical response. The objective of this study was to identify new genetic variation associated with the clinical response to anti-TNF therapy in RA. Methods: We performed a sequential multi-omic analysis integrating different sources of molecular information. First, we extracted the RNA from synovial biopsies of 11 RA patients starting anti-TNF therapy to identify gene coexpression modules (GCMs) in the RA synovium. Second, we analyzed the transcriptomic association between each GCM and the clinical response to anti-TNF therapy. The clinical response was determined at week 14 using the EULAR criteria. Third, we analyzed the association between the GCMs and anti-TNF response at the genetic level. For this objective, we used genome-wide data from a cohort of 348 anti-TNF treated patients from Spain. The GCMs that were significantly associated with the anti-TNF response were then tested for validation in an independent cohort of 2,706 anti-TNF treated patients. Finally, the functional implication of the validated GCMs was evaluated via pathway and cell type epigenetic enrichment analyses. Results: A total of 149 GCMs were identified in the RA synovium. From these, 13 GCMs were found to be significantly associated with anti-TNF response (P < 0.05). At the genetic level, we detected two of the 13 GCMs to be significantly associated with the response to adalimumab (P = 0.0015) and infliximab (P = 0.021) in the Spain cohort. Using the independent cohort of RA patients, we replicated the association of the GCM associated with the response to adalimumab (P = 0.0019). The validated module was found to be significantly enriched for genes involved in the nucleotide metabolism (P = 2.41e-5) and epigenetic marks from immune cells, including CD4+ regulatory T cells (P = 0.041). Conclusions: These findings show the existence of a drug-specific genetic basis for anti-TNF response, thereby supporting treatment stratification in the search for response biomarkers in RA.