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BackgroundThe EXXELERATE study revealed poorer clinical outcomes in patients treated with adalimumab (ADL) and baseline rheumatoid factor (RF) above 203 IU/mL. However, responses were similar in patients treated with certolizumab pegol (CZP) regardless of RF levels.ObjectivesThis study investigated the impact of RF levels >203 IU/mL on TNF inhibitors (TNFi) serum levels and the association with secondary nonresponse in RA patients treated with TNFi.MethodsWe performed an observational ambispective study with RA patients treated with infliximab (IFX), ADL, or CZP. Patients were stratified according to baseline RF levels: ≤ or >203 IU/mL. After 6 months, serum drug levels and antidrug antibodies were measured, and reasons for discontinuation were collected.ResultsWe included 170 RA patients: 90 (53%) received IFX, 48 (28%) ADL, and 32 (19%) CZP. While CZP serum levels did not differ between RF groups at 6 months (p = 0.6), RF levels >203 IU/mL were linked to lower serum drug levels in patients treated with IFX (p = 0.09) or ADL (p = 0.02). Secondary nonresponse was 3.6 times higher in patients with high versus low RF levels in patients under IFX or ADL. However, the reasons for withdrawal were not affected by RF levels in patients treated with CZP.ConclusionBaseline RF above 203 IU/mL is associated with lower serum drug levels and an increased risk of discontinuation due to secondary nonresponse in patients treated with IFX or ADL. In contrast, drug levels and clinical outcomes are not significantly impacted by baseline RF levels in patients under CZP.

Abstract Background Real world data on the response to the SARS-CoV-2 vaccine in patients with immunomediated diseases (IMIDs) treated with immunesuppressants is of great interest because vaccine response may be impaired. The main aim was to study the humoral and cellular immune response after SARS-CoV-2 vaccination in patients with IMIDs treated with immunosuppressants. The secondary aim was to describe the frequency of SARS-CoV-2 infections after vaccination in these patients. Material and methods This is an observational study including 86 patients with IMIDs. All patients were treated with biologic or targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs: TNF inhibitors (TNFi), rituximab, anti-interleukin 6 receptor (anti-IL6R) or JAK inhibitors (JAKi)]. Demographic and clinical information were collected. After 4–6 weeks of 2nd and 3rd vaccine doses, humoral response was assessed using the Thermo Scientific ELiA SARS-CoV-2-Sp1 IgG Test. Also, in patients with serum SARS-CoV-2 antibody levels under 100UI/ml, cellular response was analyzed using the QuantiFERON SARS-CoV-2 Starter Pack. Results A total of 86 patients under b/tsDMARDs and 38 healthy controls were included. Most patients received TNFi (45 with TNFi, 31 with rituximab, 5 with anti-IL6R and 5 with JAKi). SARS-CoV-2 antibodies (Ab) were present in an 86% of patients with IMIDs and in 100% healthy controls (p = 0.017). However, 12 (14%) patients had undetectable SARS-CoV-2 Ab levels, all treated with rituximab. In addition, SARS-CoV-2 Ab (IU/ml) were statistically lower in patients (Mdn (IQR): 59.5 (17–163) in patients vs 625 (405–932) in controls, p

Objectives To analyse the trajectories of Disease Activity Score 28 (DAS28), patient global assessment (PGA) and physician global assessment (PhGA) and to assess their predictive capabilities on difficult-to-treat rheumatoid arthritis (D2TRA) classification.Methods Longitudinal study of patients with rheumatoid arthritis (RA) from 2020 to 2022. Based on the D2TRA EULAR (European Alliance of Associations for Rheumatology) definition, patients were classified as D2TRA according to biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) failure due to inefficacy (D2TRA-inefficacy) or other reasons (D2TRA-other). Patients who did not fulfil the D2TRA criteria were classified as NoD2TRA. DAS28, PGA and PhGA scores collected every 6 months during the first 24 months of b/tsDMARD treatment were used to identify different trajectories using latent class mixed models (LCMM).Results The study population comprised 255 patients with RA, of whom 167 were NoD2TRA, 58 D2TRA-inefficacy and 30 D2TRA-other. LCMM stratified patients into two different trajectories for DAS28 and PhGA and three for PGA according to the most stable model. The most notable variation occurred during the first 6 months of treatment, thereafter remaining stable during the follow-up period. Most D2TRA-inefficacy patients fitted the trajectory, showing higher values of the studied parameters. NoD2TRA followed the trajectory with lower values, and D2TRA-other were distributed more homogeneously across all trajectories.Conclusions The assessment of disease activity, together with patients’ and physicians’ perceptions, form a key element in the correct discrimination of patients who are going to develop D2TRA-inefficacy. However, identifying those patients who will be D2TRA-other remains challenging, whether by subjective or objective parameters.

PURPOSETime to antibiotic administration (TTA) is a commonly used standard of care in pediatric cancer settings in high-income countries. Effective interventions to improve outcomes in cancer patients with febrile neutropenia (FN) often address timely and appropriate antibiotic administration. We assessed the effectiveness of a locally adapted multimodal strategy in decreasing TTA in a resource-constrained pediatric cancer center in Mexico.METHODSWe conducted a prospective observational study between January 2014 and April 2019. A three-phase (phase I: execution, phase II: consolidation, phase III: sustainability) multimodal improvement strategy that combined system change, FN guideline development, education, auditing and monitoring, mentoring, and dissemination was implemented to decrease TTA in inpatient and ambulatory areas. Sustainability factors were measured by using a validated tool during phases I and III.RESULTSOur population included 105 children with cancer with 204 FN events. The baseline assessment revealed that only 50% of patients received antibiotics within 60 minutes of prescription (median time: inpatient, 75 minutes; ambulatory, 65 minutes). After implementing our improvement strategy, the percentage of patients receiving antibiotics within 60 minutes of prescription increased to 88%. We significantly decreased median TTA in both clinical areas during the three phases of the study. In phase III (sustainability), the median TTA was 40 minutes (P = .023) in the inpatient area and 30 minutes (P = .012) in the ambulatory area. The proportion of patients with sepsis decreased from 30% (baseline) to 5% (phase III) (P = .001).CONCLUSIONOur results demonstrate that locally adapted multimodal interventions can reduce TTA in resource-constrained settings. Mentoring and dissemination were novel components of the multimodal strategy to improve FN-associated clinical outcomes. Improving local infrastructure, ongoing monitoring systems, and leadership engagement have been key factors to achieving sustainability during the 5-year period.

Abstract Mucin 1/Krebs von den Lungen-6 (KL-6) is proposed as a serum biomarker of several interstitial lung diseases (ILDs), including connective tissue disorders associated with ILD. However, it has not been studied in a large cohort of Caucasian antisynthetase syndrome (ASSD) patients. Consequently, we assessed the role of MUC1 rs4072037 and serum KL-6 levels as a potential biomarker of ASSD susceptibility and for the differential diagnosis between patients with ILD associated with ASSD (ASSD-ILD +) and idiopathic pulmonary fibrosis (IPF). 168 ASSD patients (149 ASSD-ILD +), 174 IPF patients and 523 healthy controls were genotyped for MUC1 rs4072037 T > C. Serum KL-6 levels were determined in a subgroup of individuals. A significant increase of MUC1 rs4072037 CC genotype and C allele frequencies was observed in ASSD patients compared to healthy controls. Likewise, MUC1 rs4072037 TC and CC genotypes and C allele frequencies were significantly different between ASSD-ILD+ and IPF patients. Additionally, serum KL-6 levels were significantly higher in ASSD patients compared to healthy controls. Nevertheless, no differences in serum KL-6 levels were found between ASSD-ILD+ and IPF patients. Our results suggest that the presence of MUC1 rs4072037 C allele increases the risk of ASSD and it could be a useful genetic biomarker for the differential diagnosis between ASSD-ILD+ and IPF patients.

Abstract The initial management of rheumatoid arthritis (RA) has a high impact on disease prognosis. Therefore, we need to select the most appropriate treatment as soon as possible. This goal requires biomarkers of disease severity and prognosis. One such biomarker may be the presence of anti-carbamylated protein antibodies (ACarPA) because it is associated with adverse long term outcomes as radiographic damage and mortality. Here, we have assessed the ACarPA as short-term prognostic biomarkers. The study was conducted in 978 prospective early arthritis (EA) patients that were followed for two years. Our results show the association of ACarPA with increased levels of all the disease activity measures in the first visit after arthritis onset. However, the associations were more significant with the high levels in local measures of inflammation and physician assessment than with the increases in systemic inflammation and patient-reported outcomes. More notably, disease activity was persistently increased in the ACarPA positive patients during the two years of follow-up. These differences were significant even after accounting for the presence of other RA autoantibodies. Therefore, the ACarPA could be considered short-term prognostic biomarkers of increased disease activity in the EA patients.

BackgroundThe International Classification of Functioning, Disability, and Health Core Sets (ICF-CSs) for schizophrenia are a set of categories for assessing functioning in persons with this health condition. This study aimed to: a) estimate the network structure of the Brief ICF-CS for schizophrenia, b) examine the community structure (categories strongly clustered together) underlying this network, and c) identify the most central categories within this network.MethodsA total of 638 health professionals from different backgrounds and with a significant role in the treatment of individuals with schizophrenia participated in a series of Delphi studies. Based on their responses we used the Ising model to estimate the network structure of the 25-category Brief ICF-CS, and then estimated the degree of centrality for all categories. Finally, the community structure was detected using the walktrap algorithm.ResultsThe resulting network revealed strong associations between individual categories within components of the ICF (i.e., Body functions, Activities and participation, and Environmental factors). The results also showed three distinct clusters of categories corresponding to the same three components. The categories e410 Individual attitudes of immediate family members, e450 Individual attitudes of health professionals, d910 Community life, and d175 Solving problems were among the most central categories in the Brief ICF-CS network.ConclusionThese results demonstrate the utility of a network approach for estimating the structure of the ICF-CSs. Implications of these results for clinical interventions and development of new instruments are discussed.

Abstract Background Biological therapies have improved the clinical course and quality of life of rheumatoid arthritis (RA) patients. Despite the availability and effectiveness of these treatments, some patients experience multiple failures to biologic disease-modifying antirheumatic drugs (bDMARDs), constituting a particular challenge to clinicians. Objectives This study aims to determine the percentage of rheumatoid arthritis (RA) patients who fail to respond to subsequent bDMARDs, describe their characteristics, and identify specific baseline and early features during the first bDMARD as possible predictors of consecutive multiple bDMARD failure. Methods This is a longitudinal study involving RA patients from the prospective biological cohort drawn from the La Paz University Hospital RA Registry (RA-Paz), starting a bDMARD during the years 2000 to 2019. Patients who presented insufficient response (due to primary or secondary inefficacy) to at least three bDMARDs or two bDMARDs with different mechanism of action were considered multi-refractory (MR-patients). Patients who achieved low disease activity or remission (by DAS-28) with the first bDMARD and maintained this over a follow-up period of at least 5 years were considered non-refractory (NR-patients). Results A total of 41 out of 402 (10%) patients were MR-patients and 71 (18%) NR-patients. In the multivariate analysis, the presence of erosions, younger age, higher baseline DAS-28 and mostly achieving delta-DAS

Objectives To determine the frequency of sustained remission (R) or low diseas activity (LDA) in patients with axial spondyloarthritis (axSpA) undergoing long-term biological therapy and to analyse predictive factors for achieving these outcomes.Design Prospective, observational cohort study.Setting Spanish hospital.Participants Patients with axSpA who initiated biological treatment between 2003 and 2017.Intervention Assessment of demographic and clinical characteristics at the beginning of treatment and disease activity every 6 months up to a maximum of 2 years.Main outcome measures Disease activity was measured by Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index and C reactive protein (BASDAI&CRP). Sustained R was defined as ASDAS

Abstract Background The patients with RA benefit from early identification soon after the first clinical symptoms appear. The 2010 ACR/EULAR classification criteria were developed to fulfill this need and their application has been demonstrated to be effective. However, there is still room for improvement. Therefore, we aimed to evaluate the potential of the concordant presence of RF, anti-CCP and anti-carbamylated protein antibodies to improve current RA classification among early arthritis (EA) patients. Methods Data from the first visit of 1057 patients in two EA prospective cohorts were used. The serological scores from the 2010 ACR/EULAR criteria and the concordant presence of the three RA autoantibodies were assessed relative to a gold standard consisting of the RA classification with the 1987 ACR criteria at the 2 years of follow-up. Results The concordant presence of three antibodies showed predictive characteristics allowing for direct classification as RA (positive predictive value = 96.1% and OR = 80.9). They were significantly better than the corresponding to the high antibody titers defined as in the 2010 classification criteria (PPV = 88.8%, OR = 26.1). In addition, the concordant presence of two antibodies was also very informative (PPV = 82.3%, OR = 15.1). These results allowed devising a scoring system based only on antibody concordance that displayed similar overall performance as the serological scoring system of the 2010 criteria. However, the best classification was obtained combining the concordance and 2010 serological systems, a combination with a significant contribution from each of the two systems. Discussion The concordant presence of RA autoantibodies showed an independent contribution to the classification of EA patients that permitted increased discrimination and precision.

The identification of “trained immunity/tolerance” in myeloid cells has changed our perception of the performance of monocytes and macrophages during inflammatory and immune responses. Pemetrexed (PMX) and methotrexate (MTX) are blockers of the one-carbon metabolism (OCM) and commonly used therapeutic agents in cancer and rheumatoid arthritis (RA). We have previously showed that MTX promotes trained immunity in human macrophages. In the present manuscript, we have assessed the anti-inflammatory effects of PMX and MTX and found that OCM blockers alter the functional and gene expression profile of human macrophages and that OCM blockade reprograms macrophages towards a state of lipopolysaccharide (LPS) tolerance at the signaling and functional levels. Moreover, OCM blockade reduced macrophage LPS responsiveness by impairing the expression of membrane-bound and soluble CD14 (sCD14). The therapeutic relevance of these results was later confirmed in early RA patients, as MTX-responder RA patients exhibit lower sCD14 serum levels, with baseline sCD14 levels predicting MTX response. As a whole, our results demonstrate that OCM is a metabolic circuit that critically mediates the acquisition of innate immune tolerance and positions sCD14 as a valuable tool to predict MTX response in RA patients.

Background: Currently, there is contradictory evidence regarding the best strategy to follow after discontinuation of a first biological agent in patients with rheumatoid arthritis (RA). We aimed to compare the long-term efficacy of switching to a second tumor necrosis factor inhibitor (TNFi) versus biopharmaceuticals with other mechanisms of action (non-TNFi) in patients with RA who previously failed a first TNFi. Methods: This prospective cohort study analyzed data from 127 patients who discontinued a previous TNFi between 1999 and 2016. Disease activity was assessed at baseline and at 6, 12, and 24 months (m-6, m-12, m-24) after switching. Primary outcome was the proportion of patients achieving good/moderate EULAR response (E-resp). Factors associated with clinical outcomes were assessed using univariate and multivariate logistic regression models. Results: Seventy-seven (61%) patients received a second TNFi and 50 (39%) switched to a non-TNFi. At m-6 and m-12, no differences were observed between groups; nevertheless, at m-24, the proportion of patients with E-resp was higher in the non-TNFi group (49% TNFi group versus 77% non-TNFi group; p = 0.002). In regression models, switching to a non-TNFi was significantly associated with E-resp at m-24 (odds ratio = 3.21; p = 0.01). When assessing the response to the second biological agent based on the reason for discontinuation of the first TNFi, similar results were obtained; at m-24, patients who discontinued the first TNFi due to inefficacy (either primary or secondary) experienced a better E-resp if they had switched to a non-TNFi (primary inefficacy: 52% TNFi group versus 79% non-TNFi group, p = 0.09; secondary inefficacy: 50% versus 76%, p = 0.03). Conclusion: In our cohort of RA patients who discontinued a first TNFi, those who switched to a non-TNFi were three times more likely to attain a sustained clinical response, regardless of whether they had discontinued the first biologic due to a primary or secondary inefficacy.

Currently, there is an increasing interest in treating patients at risk of rheumatoid arthritis (RA) to prevent the development of this chronic disease. In this sense, research has focused attention on the early identification of predictive factors of this disease. Autoantibodies and markers of systemic inflammation can be present before clinical arthritis and RA development. So, the phase of inflammatory arthralgia preceding clinical arthritis is an important part of the window of opportunity and, starting treatment might prevent progression to chronic arthritis. Additionally, the early diagnosis and treatment initiation, in patients with inflammatory arthritis at risk of persistence and/or erosive progression, are fundamental because may allow optimal clinical responses, better chances of achieving sustained remission, preventing irreversible organ damage and optimizing long-term outcomes. This review aims to give an overview of clinical risk factors for developing RA, both in suspected arthralgia and in undifferentiated arthritis. Besides taking into consideration the role of serological markers (immunological and acute phase reactants) and clinical features assessed at consultation such as: articular affection and patient's clinical perception. Other features as sociodemographic and environmental factors (lifestyle habits, microbiota, periodontal disease among others), have been included in this revision to give an insight on strategies to prevent development of RA and/or to treat it in early stages.

Criticisms of the “container” model of pregnancy picturing female and embryo as separate entities multiply in various philosophical and scientific contexts during the last decades. In this paper, we examine how this model underlies received views of pregnancy in evolutionary biology, in the characterization of the transition from oviparity to viviparity in mammals and in the selectionist explanations of pregnancy as an evolutionary strategy. In contrast, recent evo-devo studies on eutherian reproduction, including the role of inflammation and new maternal cell types, gather evidence in favor of considering pregnancy as an evolved relational novelty. Our thesis is that from this perspective we can identify the emergence of a new historical individual in evolution. In evo-devo, historical units are conceptualized as evolved entities which fulfill two main criteria, their continuous persistence and their non-exchangeability. As pregnancy can be individuated in this way, we contend that pregnant females are historical individuals. We argue that historical individuality differs from, and coexists with, other views of biological individuality as applied to pregnancy (the physiological, the evolutionary and the ecological one), but brings forward an important new insight which might help dissolve misguided conceptions.

La reificación de la identidad femenina y la expropiación de las funciones sexuales y reproductivas de las mujeres representan un elemento común de los patriarcados. Con tal finalidad, históricamente, se activaron tres discursos: irracionalización, esencialización de la identidad femenina y colonización de sus cuerpos como Naturaleza sexualizada. La enajenación de dichas funciones atrae, cada vez con mayor interés, la atención de un neoliberalismo sexual y reproductivo que encuentra en las mismas un provechoso nicho de mercado. El presente artículo aborda cómo, dichas estrategias históricas, siguen operando en el imaginario colectivo y la comunicación, analizando el caso concreto de la denominada gestación subrogada.

An integrated and interdisciplinary care system for individuals with schizophrenia is essential, which implies the need for a tool that assesses the difficulties and contextual factors of relevance to their functioning, and facilitates coordinated working across the different professions involved in their care. The International Classification of Functioning, Disability and Health Core Sets (ICF-CS) cover these requirements. This study aimed to evaluate the content validity of the ICF-CSs for schizophrenia from the perspective of experts. Six three-round Delphi studies were conducted with expert panels from different professional backgrounds which have played a significant role in the treatment of individuals with schizophrenia (psychiatry, psychology, nursing, occupational therapy, social work and physiotherapy). In total, 790 experts from 85 different countries participated in the first round. In total, 90 ICF categories and 28 Personal factors reached expert consensus (reached consensus from four or more professional perspectives). All the categories in the brief version of the ICF-CS for schizophrenia reached consensus from all the professional perspectives considered. As for the comprehensive version, 89.7% of its categories reached expert consensus. The results support the worldwide content validity of the ICF-CSs for schizophrenia from an expert perspective and underline the importance of assessing functioning by considering all the components implied.

Abstract Classification of patients with rheumatoid arthritis (RA) as quickly as possible improves their prognosis. This reason motivates specially dedicated early arthritis (EA) clinics. Here, we have used 1062 EA patients with two years of follow-up to explore the value of anti-carbamylated protein (anti-CarP) antibodies, a new type of RA specific autoantibodies, for classification. Specifically, we aimed to determine whether the addition of anti-CarP antibodies to IgM rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, which are helpful in RA classification, improves it or not. Our analysis showed that incorporation of the anti-CarP antibodies to combinations of the other two antibodies (all joint by the OR Boolean operator) produces a modest increase in sensitivity (2.2% higher), at the cost of decreased specificity (8.1% lower). The cost-benefit ratio was more favorable in the patients lacking the other autoantibodies. However, it did not improve by considering different titer levels of the anti-CarP antibodies, or after exhaustively exploring other antibody combinations. Therefore, the place in RA classification of these antibodies is questionable in the context of current treatments and biomarkers. This conclusion does not exclude their potential value for stratifying patients in joint damage, disease activity, disability, or mortality categories.

Spanish universities have a normalized presence of women and are bound by law to incorporate gender studies and a non androcentric perspective in teaching and research. Nevertheless, ceilings and glass walls remain, gender studies have not been mainstreamed and the different disciplines have androcentric views on knowledge. After the adoption of the so-called Bolonia Plan, far from implementing the legal duty, the treatment provided to gender studies in the Higher Education system has been peripheric. This article adresses this situation in public universities, highlights some problematic elements as well as possible solutions.

Resumen: En la gran mayoría de las naciones del mundo la trata con fines de explotación sexual está tipificada y castigada por la legislación penal, pese a ello se estima que entre 1,3 y 4,4 millones mujeres y niñas permanecen explotadas por las redes criminales de trata sexual. Aunque Naciones Unidas, el Consejo de Europa, la Unión Europea o la propia legislación española disponen de instrumentos normativos encaminados a la lucha contra esta modalidad de trata, el número de detenciones y el de víctimas liberadas es anecdótico y la impunidad de los tratantes es habitual. Lejos de reducirse su incidencia, se observa un proceso de expansión a escala planetaria. El presente artículo examina los factores que están contribuyendo a la expansión o incremento de la trata sexual, analiza las políticas encaminadas a la prevención, protección de las víctimas o persecución del delito desde una perspectiva multinivel para ofrecer un diagnóstico de aquellos elementos que están restando eficacia y operatividad a la acción institucional. Por último y en coherencia, concluye con algunas propuestas que permiten subsanar las disfunciones detectadas y abordar un cambio de paradigma en el diseño de las políticas contra la trata con fines de explotación sexual. Abstract: In most of the nations of the world, trafficking in women for the purpose of sexual exploitation is a crime punished by the law. Nevertheless between 1.3 and 4.4 million women and girls are estimated to be still exploited by sexual trafficking networks. Although United Nations, the Council of Europe and the European Union, or national law in Spain have instruments aimed at eradicating this type of human trafficking, the number of detained traffickers and victims made free, is a mere anecdote and impunity is usual. Far from showing a decrease in its prevalence, trafficking for the purpose of sexual exploitation is in a process of expansion in the all world. This article analyses the factors that contribute to this expansion and the policies of prevention, victims’ protection and persecution of the crime from a multilevel perspective, in order to provide a diagnosis of those elements that undermine the effectiveness and operativeness of the institutional action. Consistent with this analysis and as conclusions, the author makes some proposals to remedy the dysfunctions detected and suggest a change of paradigm in the design of policies against trafficking for the purpose of sexual exploitation.

El presente artículo aborda el debate sobre la regulación de la gestación comercial como una revisión a demanda del mercado que, bajo la falacia del libre consentimiento, incorpora una nueva clausula al Contrato Sexual. Un debate en el que procede analizar, por un lado, los límites de la mercantilización y, por otro, los requisitos éticos que permiten hablar de libre consentimiento en un contexto globalizado de feminización de la pobreza, desigualdad sexual y rearme del neoliberalismo patriarcal.

La biología sintética mantiene una relación muy singular con la teoría evolutiva: por un lado, parte de una interpretación ingenieril de la evolución para fundar su aproximación al diseño de bioartefactos; por otro, la biología sintética aspira, en última instancia, a deshacerse de la evolución creando organismos de novo que se comporten de un modo predecible. Tras examinar las tres grandes propiedades que aparecen recurrentemente en la descripción sintética de los nuevos artefactos orgánicos (su caracterización como sistemas modulares, computables y producto del diseño), argumentaré que la biología sintética se erige sobre una concepción de los organismos y en particular de la relación de estos con su legado histórico que ha sido profundamente cuestionada por la biología evolucionista contemporánea.

Schizophrenia is a severe mental disorder associated with impairment in functioning. A multidisciplinary approach is essential to help individuals with this health condition, and psychological interventions are considered a priority. The International Classification of Functioning, Disability and Health (ICF) offers a theoretical framework for assessing functioning and disability. The ICF Core Sets for schizophrenia are a list of ICF categories describing the most common problems in functioning of persons affected by this health condition. This study aimed to explore the content validity of these ICF Core Sets and to identify the most common problems in people with schizophrenia from the perspective of psychologists. Psychologists with experience of schizophrenia treatment were recruited for a three-round Delphi study in order to gather their views regarding the problems commonly presented by these patients. A total of 175 psychologists from 46 countries covering the six WHO regions answered the first-round questionnaire, and 137 completed all three rounds. The 7,526 concepts extracted from first-round responses were linked to 412 ICF categories and 53 personal factors. Consensus (≥75% agreement) was reached for 76 ICF categories and 28 personal factors. Seventy-three of the 97 ICF categories that form the Comprehensive ICF Core Set for schizophrenia achieved consensus, and only three categories that yielded consensus do not feature in this Core Set. These results support the content validity of these ICF Core Sets from the perspective of psychologists. This provides further evidence of the suitability of the ICF framework for describing functioning and disability in persons with schizophrenia.

Background: Major depression is a psychiatric disorder characterized neuropsychologically by poor performance in tasks of memory, attention, processing speed, and executive function. The aim of this systematic review was to examine the evidence regarding the neuropsychological profile of people with major depression and to determine which of two explanatory models—the processing speed hypothesis or the cognitive effort hypothesis—has most empirical support. Methods: We searched three relevant databases and reviewed the reference lists of the articles retrieved. The results obtained with the Trail Making Test and the Stroop Color-Word Test were reviewed for 37 studies published between 1993 and 2020. Results: The empirical evidence supports both hypotheses: cognitive effort and processing speed, suggesting that depression is not only characterized by psychomotor slowing but also involves a specific deficit in executive function. Discussion: We discuss potentially relevant variables that should be considered in future research in order to improve knowledge about the neurocognitive profile of depression. The main limitation of this study derives from the considerable heterogeneity of participants with MD, which makes it difficult to compare and integrate the data.

Introduction: The analysis of patients’ satisfaction with healthcare is recognised as being useful in the evaluation of health outcomes and perceived quality of care. Little is known, however, about how the psychological status of women who experience perinatal complications may affect their perceived satisfaction with care. Methods: We assessed healthcare satisfaction in 52 women who had undergone intrauterine surgery during a complicated monochorionic twin pregnancy and examined the influence that fetal loss and sociodemographic, clinical, and psychological factors had on the degree of satisfaction. Data were gathered in an individual interview and through the administration of the Medical Patient Satisfaction Questionnaire, Beck Depression Inventory, and State−Trait Anxiety Inventory. Relationships between variables were analysed using a chi-square test, Spearman’s rho, Student’s t test, and the Mann−Whitney U test, in accordance with the metric nature of the variables and the assumptions fulfilled. Results: Age and level of education were not associated with the degree of healthcare satisfaction. Negative but non-significant correlations were observed between the level of satisfaction and symptoms of anxiety and depression. Satisfaction with healthcare was high in the sample as a whole, although it was significantly higher among women who had not experienced fetal loss. There were no differences in satisfaction with services involving direct contact with medical staff, whereas satisfaction with indirect services was lower among women who had experienced perinatal loss. Conclusions: Due to the unique characteristics of this population, specialised care teams of both professional healthcare and indirect services are needed. Although administrative aspects of healthcare are regarded as being of secondary importance, this may not be the case with more vulnerable populations.

Background—The cerebellum has been recently suggested as an important player in the addiction brain circuit. Cannabis is one of the most used drugs worldwide, and its long-term effects on the central nervous system are not fully understood. No valid clinical evaluations of cannabis impact on the brain are available today. The cerebellum is expected to be one of the brain structures that are highly affected by prolonged exposure to cannabis, due to its high density in endocannabinoid receptors. We aim to use a motor adaptation paradigm to indirectly assess cerebellar function in chronic cannabis users (CCUs). Methods—We used a visuomotor rotation (VMR) task that probes a putatively-cerebellar implicit motor adaptation process together with the learning and execution of an explicit aiming rule. We conducted a case-control study, recruiting 18 CCUs and 18 age-matched healthy controls. Our main measure was the angular aiming error. Results—Our results show that CCUs have impaired implicit motor adaptation, as they showed a smaller rate of adaptation compared with healthy controls (drift rate: 19.3 +/− 6.8° vs. 27.4 +/− 11.6°; t(26) = −2.1, p = 0.048, Cohen’s d = −0.8, 95% CI = (−1.7, −0.15)). Conclusions—We suggest that a visuomotor rotation task might be the first step towards developing a useful tool for the detection of alterations in implicit learning among cannabis users.

The incorporation of women in the public sphere can be regarded as one of the most important revolutions occurred over the past century. However, it is still an incomplete revolution due to the fact that the new gender roles in the public sphere have not meant a change in the traditional roles in the private sphere. The impossibility of reconciling public and private responsibilities and the unpaid nature of the latter contribute in great measure to gender inequality. This imbalance in the distribution of time devoted to the public and the private spheres, results in the decre¬ase of competitiveness of European women in the labour market with the subsequent lower numbers of women’s employment in Europe and the precarious nature of much employment. Temporary employment, part time jobs, lower wages or occupational and sectorial segregation are the distinctive features that typify the employment of European women. Spain, in particular, has one of the most unbalanced models of the EU regarding sexual division of labour, resulting in Spanish men having the majority of paid work, while Spanish women support the weigh of most of the unpaid work. This explains Spain’s being the fourth European country with the largest gender gap inemployment (after Italy, Greece and Malta), the second in unemployment (after Greece), the third in temporary work, and its being above average concerning sectorial and occupational segregation. Segregation that has, against all logic, increased in the past few years.

ObjectiveTo examine the frequency and phenotype of Th17 cells in the peripheral blood of early RA (eRA) patients.MethodsCD4+ T cells were isolated from the peripheral blood of 33 eRA patients, 20 established RA patients and 53 healthy controls (HC), and from the synovial fluid of 20 established RA patients (RASF), by ficoll-hypaque gradient and magnetical negative selection. After polyclonal stimulation, the frequency of Th17 and Th1 cells was determined by flow cytometry and concentrations of IL-17, IFN-γ, TNF-α and IL-10 were measured by ELISA in cell-free supernatants.ResultsWhen all of our eRA patients were analyzed together, a significantly lower percentage of circulating Th17 cells and a lower CD4-derived IL-17 secretion were observed in comparison with HC. However, after stratifying by anti-CCP antibody status, circulating Th17 cells were decreased in anti-CCP(+) but not in anti-CCP(-)-eRA. All Th17 cells were CD45RO+CD45RA- and CCR6+. Dual Th17/Th1 cells were also exclusively decreased in anti-CCP(+)-eRA. Circulating Th17 and Th17/Th1 cells were negatively correlated with anti-CCP titres. When anti-CCP(+)-eRA patients were retested one year after initiating treatment with oral methotrexate, their circulating Th17 frequency was no longer different from HC. Of note, the percentage of circulating Th1 cells and the secretion of CD4-derived IFN-γ, TNF-α and IL-10 were not different between eRA patients and HC. In established RA patients, circulating Th17 and T17/Th1 cell frequencies were comparable to HC. In RASF, both Th17 and Th1 cells were increased when compared with blood of eRA patients, established RA patients and HC.ConclusionDecreased circulating Th17 levels in eRA seem to be a marker of anti-CCP seropositivity, and return to levels observed in healthy controls after treatment with methotrexate.

BACKGROUND: The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. METHODOLOGY AND RESULTS: We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5' allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01-0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = -0.27 [-0.56- -0.01], p = 0.042; TT genotype = -0.68 [-1.64- -0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. CONCLUSIONS: Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.

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