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BackgroundRheumatic and musculoskeletal diseases (RMDs) are chronic diseases that may alternate between asymptomatic periods and flares. These conditions require complex treatments and close monitoring by rheumatologists to mitigate their effects and improve the patient’s quality of life. Often, delays in outpatient consultations or the patient’s difficulties in keeping appointments make such close follow-up challenging. For this reason, it is very important to have open communication between patients and health professionals. In this context, implementing telemonitoring in the field of rheumatology has great potential, as it can facilitate the close monitoring of patients with RMDs. The use of these tools helps patients self-manage certain aspects of their disease. This could result in fewer visits to emergency departments and consultations, as well as enable better therapeutic compliance and identification of issues that would otherwise go unnoticed. ObjectiveThe main objective of this study is to evaluate the implementation of a hybrid care model called the mixed attention model (MAM) in clinical practice and determine whether its implementation improves clinical outcomes compared to conventional follow-up. MethodsThis is a multicenter prospective observational study involving 360 patients with rheumatoid arthritis (RA) and spondylarthritis (SpA) from 5 Spanish hospitals. The patients will be followed up by the MAM protocol, which is a care model that incorporates a digital tool consisting of a mobile app that patients can use at home and professionals can review asynchronously to detect incidents and follow patients' clinical evolution between face-to-face visits. Another group of patients, whose follow-up will be conducted in accordance with a traditional face-to-face care model, will be assessed as the control group. Sociodemographic characteristics, treatments, laboratory parameters, assessment of tender and swollen joints, visual analog scale for pain, and electronic patient-reported outcome (ePRO) reports will be collected for all participants. In the MAM group, these items will be self-assessed via both the mobile app and during face-to-face visits with the rheumatologist, who will do the same for patients included in the traditional care model. The patients will be able to report any incidence related to their disease or treatment through the mobile app. ResultsParticipant recruitment began in March 2024 and will continue until December 2024. The follow-up period will be extended by 12 months for all patients. Data collection and analysis are scheduled for completion in December 2025. ConclusionsThis paper aims to provide a detailed description of the development and implementation of a digital solution, specifically an MAM. The goal is to achieve significant economic and psychosocial impact within our health care system by enhancing control over RMDs. Trial RegistrationClinicalTrials.gov NCT06273306; https://clinicaltrials.gov/ct2/show/NCT06273306 International Registered Report Identifier (IRRID)PRR1-10.2196/55829

Objective To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels.Methods Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off:

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.

INTRODUÇÃO: Em 2018, um estudo de investigação realizado numa Unidade de Saúde Familiar (USF) estimou uma prevalência de défice cognitivo ligeiro (DCL) de 29,1%, verificando-se uma associação entre o melhor desempenho no teste Montreal Cognitive Assessement (MoCA) com a leitura de jornais e livros e a realização de passatempos. O objetivo do projeto foi melhorar a capacidade cognitiva nos idosos com DCL através de atividades de treino cognitivo. MÉTODOS: Projeto de intervenção realizado numa USF com uma amostra de 20 idosos com DCL. Decorreram sessões presenciais de treino cognitivo e foram entregues cadernos de trabalhos de casa. Foi aplicado o MoCA versão portuguesa aos zero, três e seis meses para avaliação do desempenho cognitivo. RESULTADOS: No início do estudo, a pontuação mediana no MoCA foi 18,5. Após seis meses, registou-se uma pontuação mediana de 23. Verificou-se uma melhoria da pontuação global em todos os domínios cognitivos, com exceção da linguagem e da orientação. CONCLUSÃO: O objetivo foi atingido pela melhoria do desempenho cognitivo após seis meses de estudo. O treino cognitivo tem um potencial efeito benéfico na saúde da população idosa e requer materiais de simples elaboração e baixo custo que podem ser aplicados em lares de idosos e centros de dia através dos cuidadores.

Abstract The social space refers to physical or virtual places where people interact with one another. It decisively influences the emergence of human behaviors. However, little is known about the nature and complexity of the social space, nor its relationship to context and spatial scale. Recently, the science of complex systems has bridged between fields of knowledge to provide quantitative responses to fundamental sociological questions. In this paper, we analyze the shifting behavior of social space in terms of human interactions and wealth distribution across multiple scales using fine-grained data collected from both official (US Census Bureau) and unofficial data sources (social media). We use these data to unveil how patterns strongly depend upon the observation scale. Therefore, it is crucial for any analysis to be framed within the appropriate context to avoid biased results and/or misleading conclusions. Biased data analysis may lead to the adoption of fragile and poor decisions. Including context and a proper understanding of the spatial scale are essential nowadays, especially with the pervasive role of data-driven tools in decision-making processes.

Abstract Background Hypophosphatasia (HPP) is a rare and underdiagnosed condition characterized by deficient bone and teeth mineralization. The aim of this study was first, to evaluate the diagnostic utility of employing alkaline phosphatase (ALP) threshold levels to identify adults with variants in ALPL among individuals with persistently low ALP levels and second, to determine the value of also including its substrates (serum pyridoxal-5′-phosphate—PLP—and urinary phosphoetanolamine-PEA) for this purpose in order to create a biochemical algorithm that could facilitate the diagnostic work-up of HPP. Results The study population comprised 77 subjects with persistent hypophosphatasaemia. They were divided into two groups according to the presence (+GT) or absence (−GT) of pathogenic ALPL variants: 40 +GT and 37 −GT. Diagnostic utility measures were calculated for different ALP thresholds and Receiver Operating Characteristic (ROC) curves were employed to determine PLP and PEA optimal cut-off levels to predict the presence of variants. The optimal threshold for ALP was 25 IU/L; for PLP, 180 nmol/L and for PEA, 30 µmol/g creatinine. Biochemical predictive models were assessed using binary logistic regression analysis and bootstrapping machine learning technique and results were then validated. For ALP 180 nmol/L) that when combined, seem to be very useful to identify individuals with ALPL variants.

Abstract The COVID-19 pandemic was an inevitable outcome of a globalized world in which a highly infective disease is able to reach every country in a matter of weeks. While lockdowns and strong mobility restrictions have proven to be efficient to contain the exponential transmission of the virus, its pervasiveness has made it impossible for economies to maintain this kind of measures in time. Understanding precisely how the spread of the virus occurs from a territorial perspective is crucial not only to prevent further infections but also to help with policy design regarding human mobility. From the large spatial differences in the behavior of the virus spread we can unveil which areas have been more vulnerable to it and why, and with this information try to assess the risk that each community has to suffer a future outbreak of infection. In this work we have analyzed the geographical distribution of the cumulative incidence during the first wave of the pandemic in the region of Galicia (north western part of Spain), and developed a mathematical approach that assigns a risk factor for each of the different municipalities that compose the region. This risk factor is independent of the actual evolution of the pandemic and incorporates geographic and demographic information. The comparison with empirical information from the first pandemic wave demonstrates the validity of the method. Our results can potentially be used to design appropriate preventive policies that help to contain the virus.

Abstract To analyze the epidemiology, clinical features and costs of hospitalized patients with gout during the last decade in Spain. Retrospective observational study based on data from the Minimum Basic Data Set (MBDS) from the Spanish National Health Service database. Patients ≥ 18 years with any gout diagnosis at discharge who had been admitted to public or private hospitals between 2005 and 2015 were included. Patients were divided in two periods: p1 (2005–2010) and p2 (2011–2015) to compare the number of hospitalizations, mean costs and mortality rates. Data from 192,037 patients with gout was analyzed. There was an increase in the number of hospitalized patients with gout (p

Abstract Immunogenicity related to treatment with TNF inhibitors (TNFi) is one of the causes for the decreased attainment of clinical response in patients with rheumatoid arthritis (RA). The B-cell activating factor (BAFF) may be playing a role in the development of immunogenicity. The objective of this study was to analyse the association of baseline concentration of serum B-cell activating factor (BAFF) with immunogenicity after 6 months of TNFi treatment. A total of 127 patients with RA starting a TNFi (infliximab, adalimumab, certolizumab pegol or golimumab) were followed-up for 6 months. Serum samples were obtained at baseline and at 6 months and anti-drug antibody (ADA) and BAFF concentrations were measured. Logistic regression models were employed in order to analyse the association between BAFF concentrations and immunogenicity. Receiver operating characteristic analysis was performed to determine the BAFF concentrations with a greater likelihood of showing immunogenicity association. At 6 months, 31 patients (24%) developed ADA. A significant interaction between the age and baseline BAFF concentration was found for the development of ADA (Wald chi-square value = 5.30; p = 0.02); therefore, subsequent results were stratified according to mean age (≤ / > 55 years). Baseline serum BAFF concentration was independently associated with ADA development only in patients over 55 years (OR = 1.51; 95% CI 1.03–2.21). Baseline serum BAFF ≥ 1034 pg/mL predicted the presence of ADA at 6 months (AUC = 0.81; 95% confidence interval (CI) 0.69–0.93; p = 0.001; positive likelihood ratio = 3.7). In conclusion, our results suggest that the association of BAFF concentration and immunogenicity depends on the patient’s age. Baseline serum BAFF concentration predicts the presence of ADA within 6 months of TNFi therapy in older patients with RA.

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.

Abstract The present study used 16S rRNA gene amplicon sequencing to assess the impact on salivary microbiome of different grades of dental and periodontal disease and the combination of both (hereinafter referred to as oral disease), in terms of bacterial diversity, co-occurrence network patterns and predictive models. Our scale of overall oral health was used to produce a convenience sample of 81 patients from 270 who were initially recruited. Saliva samples were collected from each participant. Sequencing was performed in Illumina MiSeq with 2 × 300 bp reads, while the raw reads were processed according to the Mothur pipeline. The statistical analysis of the 16S rDNA sequencing data at the species level was conducted using the phyloseq, DESeq2, Microbiome, SpiecEasi, igraph, MixOmics packages. The simultaneous presence of dental and periodontal pathology has a potentiating effect on the richness and diversity of the salivary microbiota. The structure of the bacterial community in oral health differs from that present in dental, periodontal or oral disease, especially in high grades. Supragingival dental parameters influence the microbiota’s abundance more than subgingival periodontal parameters, with the former making a greater contribution to the impact that oral health has on the salivary microbiome. The possible keystone OTUs are different in the oral health and disease, and even these vary between dental and periodontal disease: half of them belongs to the core microbiome and are independent of the abundance parameters. The salivary microbiome, involving a considerable number of OTUs, shows an excellent discriminatory potential for distinguishing different grades of dental, periodontal or oral disease; considering the number of predictive OTUs, the best model is that which predicts the combined dental and periodontal status.

Objetivo: Evaluar la densidad mineral ósea (DMO) y parámetros de 3D-Shaper a nivel de fémur proximal (FP) en adultos con hipofosfatasia (HPP) confirmada genéticamente y compararlos en aquellos sujetos con y sin fracturas. Material y métodos: Análisis transversal de datos densitométricos y de arquitectura ósea de la visita basal de un estudio longitudinal en el que se incluyeron pacientes con HPP. Se realizó un estudio densitométrico (Lunar Prodigy, GE iDXA) en FP y se empleó el software 3D-Shaper (version 2,7. Galgo Medical). Resultados: Se incluyeron 33 adultos con HPP con mutaciones en heterocigosis. Un 63,6% (21/33) fueron mujeres (42,9% postmenopáusicas), y 8 de los varones (66,6%) fueron mayores de 50 años. La media de edad fue 50,56±15,08 años, el 30,3% (10/33) tuvieron fracturas previas traumáticas, y un 15,2% (5/33), de estrés. La prevalencia de osteoporosis en CF fue del 11,8% (2/17) y de osteopenia, 82,4% (14/17). En premenopáusicas y varones jóvenes se detectó baja masa ósea para la edad en un 12,5% (2/16). Al comparar sujetos con fracturas de estrés y sin ellas, así como con traumáticas, no hubo diferencias en DMO. El 3D-Shaper mostró disminución del grosor cortical (mm) en pacientes con fracturas de estrés [1,8 (1,77-1,89)] frente a sujetos sin ellas [1,94 (1,87-2,03, p=0,03)] y en comparación con los que tuvieron fracturas traumáticas [1,97 (1,88-2,04), p=0,03]. Conclusiones: Estos datos reflejan una discreta repercusión densitométrica en formas más leves del adulto. Estudios de arquitectura ósea pudieran resultar de interés para determinar pacientes susceptibles de presentar fracturas de estrés.

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 Hypophosphatasia (HPP) is an inborn error of metabolism characterized by low levels of serum alkaline phosphatase (ALP). Scarce evidence exists about features that should signal the potential association between hypophosphatasaemia and HPP in adults. The aim of this study is to estimate the prevalence of ALPL variants in subjects with persistent hypophosphatasaemia and determine the associated clinical and laboratory features. For this cross-sectional study, laboratory records of 386,353 subjects were screened by measurement of ALP activity. A total of 85 (0.18%) subjects with persistent hypophosphatasaemia (≥2 serum alkaline phosphatase–ALP–measurements ≤35 IU/L and none > 45 IU/L) were included (secondary causes previously discarded). ALPL genetic testing and a systematized questionnaire to retrieve demographic, clinical and laboratory data were performed. Descriptive analysis and logistic regression models were employed to identify the clinical and laboratory characteristics associated with ALPL variants. Results Forty subjects (47%) had a variant(s) in ALPL. With regard to clinical characteristics, the presence of an ALPL variant was significantly associated only with musculoskeletal pain (OR: 7.6; 95% IC: 1.9–30.9). Nevertheless, a trend to present more dental abnormalities (OR: 3.6; 95% IC: 0.9–13.4) was observed. Metatarsal stress fractures were also more frequent (4 vs 0; p

BackgroundConversational agents, which we defined as computer programs that are designed to simulate two-way human conversation by using language and are potentially supplemented with nonlanguage modalities, offer promising avenues for health interventions for different populations across the life course. There is a lack of open-access and user-friendly resources for identifying research trends and gaps and pinpointing expertise across international centers. ObjectiveOur aim is to provide an overview of all relevant evidence on conversational agents for health and well-being across the life course. Specifically, our objectives are to identify, categorize, and synthesize—through visual formats and a searchable database—primary studies and reviews in this research field. MethodsAn evidence map was selected as the type of literature review to be conducted, as it optimally corresponded to our aim. We systematically searched 8 databases (MEDLINE; CINAHL; Web of Science; Scopus; the Cochrane, ACM, IEEE, and Joanna Briggs Institute databases; and Google Scholar). We will perform backward citation searching on all included studies. The first stage of a double-stage screening procedure, which was based on abstracts and titles only, was conducted by using predetermined eligibility criteria for primary studies and reviews. An operational screening procedure was developed for streamlined and consistent screening across the team. Double data extraction will be performed with previously piloted data collection forms. We will appraise systematic reviews by using A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2. Primary studies and reviews will be assessed separately in the analysis. Data will be synthesized through descriptive statistics, bivariate statistics, and subgroup analysis (if appropriate) and through high-level maps such as scatter and bubble charts. The development of the searchable database will be informed by the research questions and data extraction forms. ResultsAs of April 2021, the literature search in the eight databases was concluded, yielding a total of 16,351 records. The first stage of screening, which was based on abstracts and titles only, resulted in the selection of 1282 records of primary studies and 151 records of reviews. These will be subjected to second-stage screening. A glossary with operational definitions for supporting the study selection and data extraction stages was drafted. The anticipated completion date is October 2021. ConclusionsOur wider definition of a conversational agent and the broad scope of our evidence map will explicate trends and gaps in this field of research. Additionally, our evidence map and searchable database of studies will help researchers to avoid fragmented research efforts and wasteful redundancies. Finally, as part of the Harnessing the Power of Conversational e-Coaches for Health and Well-being Through Swiss-Portuguese Collaboration project, our work will also inform the development of an international taxonomy on conversational agents for health and well-being, thereby contributing to terminology standardization and categorization. International Registered Report Identifier (IRRID)DERR1-10.2196/26680

[This corrects the article DOI: 10.1371/journal.pone.0254193.].

In recent years, the Asian gall wasp Dryocosmus kuriphilus has invaded chestnut trees and significantly affected the Portuguese chestnut production. Studies in other countries, such as Japan or Italy, have shown that the parasitoid Torymus sinensis can successfully achieve biological control of D. kuriphilus. Mathematical models help us to understand the dynamics of the interaction between the pest D. kuriphilus and its parasitoid T. sinensis and, consequently, they can help to implement measures that enhance crop pest management. In this work, the evolution of the density of D. kuriphilus and T. sinensis across time and space is studied through the numerical solution of models that include parameters based on observations made in Portugal. Simultaneous releases of the parasitoid are simulated at various locations and at different times. The results indicate that, in the case of a small and homogeneous orchard, biological control can be effective, but, in the case of extensive domains, the pest control is much more difficult to achieve. In order for biological control to be efficient, it is necessary to implement, in each chestnut-producing region, a collective strategy based on the annual monitoring of infestation levels.

Introduction Virtual Communities of Practice (VCoP) or knowledge-sharing virtual communities offer ubiquitous access to information and exchange possibilities for people in similar situations, which might be especially valuable for the self-management of patients with chronic diseases. In view of the scarce evidence on the clinical and economic impact of these interventions on chronic conditions, we aim to evaluate the effectiveness and cost-effectiveness of a VCoP in the improvement of the activation and other patient empowerment measures in patients with ischaemic heart disease (IHD).Methods and analysis A pragmatic randomised controlled trial will be performed in Catalonia, Madrid and Canary Islands, Spain. Two hundred and fifty patients with a recent diagnosis of IHD attending the participating centres will be selected and randomised to the intervention or control group. The intervention group will be offered participation for 12 months in a VCoP based on a gamified web 2.0 platform where there is interaction with other patients and a multidisciplinary professional team. Intervention and control groups will receive usual care. The primary outcome will be measured with the Patient Activation Measure questionnaire at baseline, 6, 12 and 18 months. Secondary outcomes will include: clinical variables; knowledge (Questionnaire of Cardiovascular Risk Factors), attitudes (Self-efficacy Managing Chronic Disease Scale), adherence to the Mediterranean diet (Mediterranean Diet Questionnaire), level of physical activity (International Physical Activity Questionnaire), depression (Patient Health Questionnaire), anxiety (Hospital Anxiety Scale-A), medication adherence (Adherence to Refill Medication Scale), quality of life (EQ-5D-5L) and health resources use. Data will be collected from self-reported questionnaires and electronic medical records.Ethics and dissemination The trial was approved by Clinical Research Ethics Committee of Gregorio Marañón University Hospital in Madrid, Nuestra Señora de Candelaria University Hospital in Santa Cruz de Tenerife and IDIAP Jordi Gol in Barcelona. The results will be disseminated through workshops, policy briefs, peer-reviewed publications, local/international conferences.Trial registration number ClinicalTrials.gov Registry (NCT03959631). Pre-results.

Objective Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder with a global prevalence of approximately 0.5–1%. Patients with RA are at an increased risk of developing comorbidities (eg, cardiovascular disease, pulmonary disease, diabetes and depression). Despite this, there are limited recommendations for the management and implementation of associated comorbidities. This study aimed to identify good practice interventions in the care of RA and associated comorbidities.Methods A combination of primary research (180+ interviews with specialists across 12 European rheumatology centres) and secondary research (literature review of existing publications and guidelines/recommendations) were used to identify challenges in management and corresponding good practice interventions. Findings were prioritised and reviewed by a group of 18 rheumatology experts including rheumatologists, comorbidity experts, a patient representative and a highly specialised nurse.Results Challenges throughout the patient pathway (including delays in diagnosis and referral, shortage of rheumatologists, limited awareness of primary care professionals) and 18 good practice interventions were identified in the study. The expert group segmented and prioritised interventions according to three distinct stages of the disease: (1) suspected RA, (2) recent diagnosis of RA and (3) established RA. Examples of good practice interventions included enabling self-management (self-monitoring and disease management support, for example, lifestyle adaptations); early arthritis clinic; rapid access to care (online referral, triage, ultrasound-guided diagnosis); dedicated comorbidity specialists; enhanced communication with primary care (hotline, education sessions); and integrating patient registries into daily clinical practice.Conclusion Learning from implementation of good practice interventions in centres across Europe provides an opportunity to more widely improved care for patients with RA and associated comorbidities.

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.

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPs.

Background. Human T-cell lymphotropic virus type 1 (HTLV-1) is responsible for tropical spastic paraparesis and HTLV-1-associated leukemia/lymphoma. The infection is endemic in some areas of Peru, but its prevalence in the Peruvian Amazon is not well established. We aimed to assess the seroprevalence of HTLV-1 infection in pregnant women in the Peruvian Amazon. Moreover, we performed a systematic literature review and meta-analysis of the seroprevalence of HTLV infection in Peru. (2) Methods. This is a prospective cross-sectional study involving pregnant women attending health centers in the city of Iquitos, Peru, in May and June 2019. The presence of antibodies against HTLV-1 was assessed using ELISA (HTLV I + II ELISA recombinant v.4.0, Wiener lab, Rosario, Argentina). Positive cases were confirmed by Western Blot and HTLV-1 proviral load. (3) Results. The study included 300 pregnant women with a mean age of 26 years (standard deviation [SD] 6.4). Five patients were diagnosed with HTLV-1 infection (prevalence 1.7%, 95% confidence interval (CI) 0.7% to 3.8%). Pregnant women with HTLV-1 infection were discretely younger (mean age 22.6 [SD 22.6] vs. 26.8 [SD 6.3]; p = 0.128). None of the five women had been transfused, and all were asymptomatic. Two (40%) also had a positive serology for Strongyloides, but larvae were not detected in any of the parasitological stool studies. The systematic review component identified 40 studies, which showed that the prevalence of HTLV infection in the general population was 2.9% (95% CI 1.2% to 5.3%) and in women of childbearing age, 2.5% (95% CI 1.2% to 4.0%). (4) Conclusion. The prevalence of HTLV-1 in the Peruvian Amazon basin is about 1.7%, indicating an endemic presence. Screening for HTLV-1 in prenatal care is warranted.

Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi.

Background: Reducing the dose of biological therapy (BT) when patients with immune-mediated arthritis achieve a sustained therapeutic goal may help to decrease costs for national health services and reduce the risk of serious infection. However, there is little information about whether such a decision can be applied universally. Therefore, the objective of this study was to develop appropriateness criteria for reducing the dose of BT in patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and peripheral spondyloarthritis (pSpA). Methods: The RAND/UCLA appropriateness method was coordinated by experts in the methodology. Five rheumatologists with clinical research experience in RA and/or SpA selected and precisely defined the variables considered relevant when deciding to reduce the dose of BT in the 3 diseases, in order to define patient profiles. Ten rheumatologists with experience in prescribing BT anonymously rated each profile on a scale of 1 (completely inappropriate) to 9 (completely appropriate) after revising a summary of the evidence obtained from 4 systematic literature reviews carried out specifically for this project. Findings: A total of 2,304 different profiles were obtained for RA, 768 for axSpA, and 3,072 for pSpA. Only 327 (14.2%) patient profiles in RA, 80 (10.4%) in axSpA, and 154 (5%) in pSpA were considered appropriate for reducing the dose of BT. By contrast, 749 (32.5%) patient profiles in RA, 270 (35.3%) in axSpA, and 1,243 (40.5%) in pSpA were considered inappropriate. The remaining profiles were considered uncertain. Interpretation: Appropriateness criteria for reducing the dose of BT were developed in 3 inflammatory conditions. These criteria can help clinicians treating these disorders to optimize the BT dose. However, further research is needed, since more than 50% of the profiles were considered uncertain and the real prevalence of each profile in daily clinical practice remains unknown.