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Objectives The aim of this study is to evaluate risk factors for severe coronavirus disease 2019 (COVID-19) in patients with immune-mediated rheumatic diseases, stratified by systemic autoimmune conditions and chronic inflammatory arthritis. Methods An observational, cross-sectional multicentre study was performed. Patients from 10 rheumatology departments in Madrid who presented with severe acute respiratory syndrome coronavirus-2 infection between February 2020 and May 2021 were included. The main outcome was COVID-19 severity (hospital admission or mortality). Risk factors for severity were estimated, adjusting for covariates (socio-demographic, clinical, and treatments), using logistic regression analyses. Results In total, 523 patients with COVID-19 were included, among whom 192 (35.6%) patients required hospital admission and 38 (7.3%) died. Male gender, older age, and comorbidities such as diabetes mellitus, hypertension, and obesity were associated with severe COVID-19. Corticosteroid doses >10 mg/day, rituximab, sulfasalazine, and mycophenolate use, were independently associated with worse outcomes. COVID-19 severity decreased over the different pandemic waves. Mortality was higher in the systemic autoimmune conditions (univariate analysis, P Conclusions This study confirms and provides new insights regarding the harmful effects of corticosteroids, rituximab, and other therapies (mycophenolate and sulfasalazine) in COVID-19. Methotrexate and anti-tumour necrosis factor therapy were not associated with worse outcomes.

Psoriasis is a common skin disease. Up to 30% of patients with psoriasis develop psoriatic arthritis (PsA) resulting, by far, the most prevalent coexisting condition. Heterogeneity of clinical and radiological presentation is a major challenge to diagnosis of PsA. Initial reports about PsA emphasized a benign course in most patients, but it is now recognized that psoriatic arthritis often leads to impaired function and a reduced quality of life. PsA is a progressive disease characterized by diverse clinical features, often resulting in diagnostic delay and treatment that are associated with poor clinical and structural outcomes. New effective treatments may halt PsA progression, and consequently, treatment goals have evolved from simple reduction of pain to achieving full remission or minimal disease activity. This emerging treat-to-target strategy paradigm emphasize a need for early diagnosis; sensitive imaging techniques may be of value in this process. While radiography and CT depict structural damage, US and MRI have emerged as helpful tools to evaluate magnitude and severity of active inflammatory lesions. This review aims to describe the role of imaging modalities in diagnosis, follow-up and prognosis of PsA.

Introduction Psoriatic arthritis (PsA) is considered a multifaceted disease, with patients reporting low health-related quality of life (HRQoL). Data on disease burden are substantial and there exists a need for properly designed studies to learn more about the evolution of HRQoL in this condition. This study aims to identify factors associated to HRQoL evolution in PsA patients followed-up in a real-world setting in Spain. Methods We conducted a retrospective longitudinal observational study including incident patients from the rheumatology outpatient clinic of Hospital Clínico San Carlos (Madrid, Spain), diagnosed for the first time of PsA, defined as having received any ICD9/ICD10 diagnosis code of PsA, from 2007 to 2016, and followed-up until loss of follow-up, death, or November 2017. The influence of demographic and clinical variables in baseline HRQoL [assessed with the Rosser Classification Index (RCI)] was analyzed using bivariable and multivariable generalized linear models. The influence of those variables and of treatment-related factors in repeated measures of HRQoL was analyzed using bivariable and multivariable generalized estimating equations (GEE) models nested by patient. Results Two hundred and thirty patients were included in the analysis, with 3384 registered visits. At baseline, older age, a previous diagnosis of obesity, and the presence of enthesitis were significantly associated with worse HRQoL. During follow-up, using an exchangeable working correlation structure, the presence of enthesitis was also associated with worse HRQoL, coefficient (95% CI) − 0.006 (− 0.01 to − 0.002), p = 1.00E−03; conversely, treatment with methotrexate or antimalarials was associated with better HRQoL with 0.007 (0.001–0.014), p = 0.020 and 0.003 (0.001–0.005), p = 3.00E−03, respectively. Conclusions Musculoskeletal manifestations and comorbidities exert a deleterious effect in HRQoL of PsA patients. Therefore, the optimal management of this condition needs to also address these manifestations in order to try to restore the QoL of these patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00349-1.

Background To assess mortality rate (MR) and standardized mortality rate (SMR) of rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients and to evaluate the role of radiographic patterns in mortality. Methods A longitudinal multicentric study was conducted in RA-ILD patients from 2005 to 2015 and followed-up until October 2018 in Madrid. Patients were included in the Neumologia-Reumatología y Enfermedades Autoinmunes Registry, from diagnosis of ILD. The main outcome was all-cause mortality. The radiographic pattern at baseline [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), or others] was the independent variable. Covariables included sociodemographic and clinical data. Survival techniques were used to estimate MR, expressed per 1000 persons-year with their 95% confidence intervals [CI]. Cox multiple regression model was run to examine the influence of radiographic patterns on survival. SMR [CI] was calculated comparing MR obtained with MR expected in the general population of Madrid by indirect age-gender standardization. Results 47 patients were included with a follow-up 242 patients-year. There were 16 (34%) deaths, and most frequent causes were acute ILD exacerbation and pneumonia. MR was 64.3 [39.4–104.9], and 50% of the patients died at 8.3 years from ILD diagnosis. After adjusting for confounders, (UIP compared to NSIP was associated with higher mortality risk. The overall SMR was 2.57 [1.4–4.17]. Women of 60–75 years of age were the group with the highest SMR. Conclusions RA-ILD is associated with an excess of mortality compared to general population. Our results support that UIP increases the risk of mortality in RA-ILD, regardless other factors.

SARS-CoV-2; Post-mortem microbiology; Volutrauma SARS-CoV-2; Microbiología post mortem; Volutrauma SARS-CoV-2; Microbiologia post mortem; Volutrauma Background and Objective: A thorough understanding of the pathogenic mechanisms elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still requires further research. Until recently, only a restricted number of autopsies have been performed, therefore limiting the accurate knowledge of the lung injury associated with SARS-CoV-2. A multidisciplinary European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group of Forensic and Post-mortem Microbiology-ESGFOR team conducted a non-systematic narrative literature review among coronavirus 2019 disease (COVID-19) pneumonia cases assessing the histopathological (HP) effects of positive airways pressure. HP lung features were recorded and compared between mechanically ventilated (>24 hours) and control (ventilation 24 hours as an independent variable associated with DAD (OR =5.40, 95% CI: 1.48–19.62), fibrosis (OR =3.88, 95% CI: 1.25–12.08), vascular damage (OR =5.49, 95% CI: 1.78–16.95) and association of DAD plus fibrosis plus vascular damage (OR =6.99, 95% CI: 2.04–23.97). Conclusions: We identified that patients mechanically ventilated >24 hours had a significantly higher rate of pulmonary injury on histopathology independently of age and gender. Our findings emphasize the importance of maintaining a protective ventilator strategy when subjects with COVID-19 pneumonia undergo intubation.

ObjectivesMost studies on difficult-to-treat rheumatoid arthritis (D2T RA) have focused on established RA. Here, we analyze whether disease activity in the early stages of RA could influence progression to a D2T RA under real-life conditions. Other clinical and treatment-related factors were also analyzed.MethodsA longitudinal multicenter study of RA patients was conducted from 2009 to 2018. Patients were followed up until January 2021. D2T RA was defined based on EULAR criteria (treatment failure, signs suggestive of currently active/progressive disease, and management being perceived as problematic by the rheumatologist and/or patient). The main outcome was disease activity in the early stages. The covariates were sociodemographic, clinical, and treatment-related factors. We ran a multivariable logistic regression analysis to investigate risk factors associated with progression to D2T RA. Weighting techniques were also applied to balance data.ResultsThe study population comprised 631 patients and 35 developed D2T RA. At the time of diagnosis, the D2T RA group were younger, with a higher disability, DAS28 score, tender joint count and pain scores. In our final model, DAS28 was not statistically significantly associated with D2T RA. No differences were found between groups for therapy. Disability was independently associated with D2T RA (OR: 1.50; p=0.02).ConclusionsIn this cohort of patients newly diagnosed with RA, our results do not allow us to prove the influence of active disease according to DAS28. However, we did find that patients with elevated initial disability scores are more likely to develop D2T RA regardless of other factors.What is already known on this topicDespite T2T and the availability of a range of advanced therapies, D2T RA remains a relevant clinical problem. Evidence for the D2T RA population have focused on established RA. The aim of our study was to analyze whether disease activity at diagnosis could influence progression to D2T RA under real-life conditions.What this study addsWe did find that patients with elevated initial disability scores are more likely to develop D2T RA regardless of other factors.How this study might affect research, practice or policyThe implementation of more effective strategies in the early stages of the disease and focused on the most influential factors, including severe disability, may change disease course and prevent D2T RA.

ObjectivesTo describe patients with autoimmune inflammatory rheumatic diseases (AIRD) who had COVID-19 disease; to compare patients who required hospital admission with those who did not and assess risk factors for hospital admission related to COVID-19.MethodsAn observational longitudinal study was conducted during the pandemic peak of severe acute respiratory syndrome coronavirus 2 (1 March 2020 to 24 April). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid, Spain with a medical diagnosis of AIRD and with symptomatic COVID-19 were included. The main outcome was hospital admission related to COVID-19. The covariates were sociodemographic, clinical and treatments. We ran a multivariable logistic regression model to assess risk factors for the hospital admission.ResultsThe study population included 123 patients with AIRD and COVID-19. Of these, 54 patients required hospital admission related to COVID-19. The mean age on admission was 69.7 (15.7) years, and the median time from onset of symptoms to hospital admission was 5 (3–10) days. The median length of stay was 9 (6–14) days. A total of 12 patients died (22%) during admission. Compared with outpatients, the factors independently associated with hospital admission were older age (OR: 1.08; p=0.00) and autoimmune systemic condition (vs chronic inflammatory arthritis) (OR: 3.55; p=0.01). No statistically significant findings for exposure to disease-modifying antirheumatic drugs were found in the final model.ConclusionOur results suggest that age and having a systemic autoimmune condition increased the risk of hospital admission, whereas disease-modifying antirheumatic drugs were not associated with hospital admission.

ObjectivesTo asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated.MethodsA longitudinal multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry [pNEumology RhEumatology Autoinmune diseases (NEREA)] from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6–12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI.ResultsA total of 68 patients were included. FI occurred in 42 patients [IR 23.5 (95% CI 19, 29.1)] and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure [HR 0.51 (95% CI 0.31, 0.85)]. Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI.ConclusionRA-ILD patients deteriorate over time, with the median time free of impairment being

Objectives We aimed to describe persistent symptoms and sequelae in patients with rheumatic and musculoskeletal diseases (RMD) after admission owing to coronavirus disease 2019 (COVID-19), assessing the role of autoimmune rheumatic diseases (ARDs) compared with non-autoimmune rheumatic and musculoskeletal diseases (NARDs) on persistent symptoms and sequelae. Methods We performed an observational study including RMD patients who attended a rheumatology clinic in Madrid and required admission owing to COVID-19 (between March and May 2020) and survived. The study began at discharge and ran until October 2020. Main outcomes were persistence of symptoms and sequelae related to COVID-19. The independent variable was the RMD group (ARD and NARD). Covariates included sociodemographics, clinical and treatment data. We ran a multivariate logistic regression model to assess the risk of the main outcomes by RMD group. Results We included 105 patients, of whom 51.5% had ARD and 68.57% reported at least one persistent symptom. The most frequent symptoms were dyspnoea, fatigue and chest pain. Sequelae were recorded in 31 patients. These included lung damage in 10.4% of patients, lymphopenia in 10%, a central retinal vein occlusion and an optic neuritis. Two patients died. Eleven patients required re-admission owing to COVID-19 problems (16.7% ARD vs 3.9% NARD; P = 0.053). No statistically significant differences were found between RMD groups in the final models. Conclusion Many RMD patients have persistent symptoms, as in other populations. Lung damage is the most frequent sequela. Compared with NARD, ARD does not seem to differ in terms of persistent symptoms or consequences, although ARD might have more re-admissions owing to COVID-19.

Introduction: Rheumatic and musculoskeletal diseases (RMDs) have a significant impact on patients’ health-related quality of life (HRQoL) exacerbating disability, reducing independence and work capacity, among others. Predictors’ identification affecting HRQoL could help to place efforts that minimize the deleterious impact of these conditions on patients’ wellbeing. This study evaluates the influence of demographic and clinical predictors on the HRQoL of a cohort of RMD patients, measured using the Rosser classification index (RCI). Methods: We included patients attending the Hospital Clínico San Carlos (HCSC) rheumatology outpatient clinic from 1 April 2007 to 30 November 2017. The primary outcome was the HRQoL assessed in each of the patient’s visits using the RCI. Demographic and clinical variables extracted from a departmental electronic health record (EHR) were used as predictors: RMD diagnoses, treatments, comorbidities, and averaged HRQoL values from previous periods (for this last variable, values were imputed if no information was available). Association between predictors and HRQoL was analyzed using penalized generalized estimating equations (PGEEs). To account for imputation bias, the PGEE model was repeated excluding averaged HRQoL predictors, and common predictors were considered. Discussion: A total of 18,187 outpatients with 95,960 visits were included. From 410 initial predictors, 19 were independently associated with patients’ HRQoL in both PGEE models. Chronic kidney disease (CKD), an episode of prescription of third level analgesics, monoarthritis, and fibromyalgia diagnoses were associated with worse HRQoL. Conversely, the prescription in the previous visit of acid-lowering medication, colchicine, and third level analgesics was associated with better HRQoL. Conclusion: We have identified several diagnoses, treatments, and comorbidities independently associated with HRQoL in a cohort of outpatients attending a rheumatology clinic.

Background: Mesenchymal stem cells (MSCs) are a promising treatment of different musculoskeletal diseases including osteoarthritis and rheumatoid arthritis (RA). Results from different approaches in this treatment have been not conclusive. Aim: To analyze factors related to interactions between peripheral blood mononuclear cells (PBMCs) and MSCs and the influence of cellular activation. Materials & methods: PBMCs from RA patients and healthy controls (HC) were obtained. MSCs from bone marrow (BM-MSCs) were obtained from six donors. CD4, CD25, CD69 and CD127 expression was measured by flow cytometry. Repeated measures analysis of variance (ANOVA) models were performed using activation, co-culture with BM-MSCs and time of culture (24 h, 72 h, 6 days) as within-subject variables. Results: PBMCs activated and co-cultured with BM-MSCs showed a lower proportion of CD25-positive and CD25high/CD127low-negative cells in both RA and HC. Additionally, a maintained expression of CD69 was also observed in RA and HC when PBMCs were activated and co-cultured with BM-MSCs. Conclusion: Both PBMC activation grade and RA disease activity influence the immunomodulatory effect of BM-MSCs on T-cell activation.

BackgroundClinical studies with work participation (WP) as an outcome domain pose particular methodological challenges that hamper interpretation, comparison between studies and meta-analyses.ObjectivesTo develop Points to Consider (PtC) for design, analysis and reporting of studies of patients with inflammatory arthritis that include WP as a primary or secondary outcome domain.MethodsThe EULAR Standardised Operating Procedures were followed. A multidisciplinary taskforce with 22 experts including patients with rheumatic diseases, from 10 EULAR countries and Canada, identified methodologic areas of concern. Two systematic literature reviews (SLR) appraised the methodology across these areas. In parallel, two surveys among professional societies and experts outside the taskforce sought for additional methodological areas or existing conducting/reporting recommendations. The taskforce formulated the PtC after presentation of the SLRs and survey results, and discussion. Consensus was obtained through informal voting, with levels of agreement obtained anonymously.ResultsTwo overarching principles and nine PtC were formulated. The taskforce recommends to align the work-related study objective to the design, duration, and outcome domains/measurement instruments of the study (PtC: 1–3); to identify contextual factors upfront and account for them in analyses (PtC: 4); to account for interdependence of different work outcome domains and for changes in work status over time (PtC: 5–7); to present results as means as well as proportions of patients reaching predefined meaningful categories (PtC: 8) and to explicitly report volumes of productivity loss when costs are an outcome (PtC:9).ConclusionAdherence to these EULAR PtC will improve the methodological quality of studies evaluating WP.

OBJECTIVESTo describe persistent symptoms and consequences in Rheumatic and Musculoskeletal diseases (RMD) discharged from the hospital after Covid-19; to assess the roll of autoimmune rheumatic diseases (ARD) compared to and non-autoimmune rheumatic and musculoskeletal diseases (NARD) on persistent symptoms and consequences.METHODSWe performed a cross-sectional observational study. RMD attended at a rheumatology outpatient clinic in Madrid with Covid-19 that required hospital admission were included. The main outcomes were persistence of symptoms and health consequences related to Covid19 after discharge. Independent variable was RMD group (ARD and NARD) and covariates were sociodemographic, clinical, and treatments. We ran a multivariable logistic regression model to assess the risk by RMD group on main outcomes.RESULTSWe included 105 patients and 51.5% had ARD. 68.57% reported at least one persistent symptom. The most frequent were dyspnea, fatigue, and chest pain. 31 patients had consequences. Lung damage was found in 11.4% of the patients, 18% had blood test abnormalities (10% lymphopenia), two died, one developed central retinal vein occlusion and one patient developed optic neuritis. 11 patients required readmission due to Covid-19 problems (16.7% ARD vs 3.9% NARD; p=0.053). No statistically significant differences by RMD groups were found in the final models.CONCLUSIONMany RMD patients have persistent symptoms, similar to other populations. This study also highlights that lung damage is the most frequent consequence. ARD compared to NARD does not seem to differ in terms of persistent symptoms or consequences, although ARD might have a greater number of readmissions due to Covid-19.

Aims: In this pandemic, it is essential for rheumatologists and patients to know the relationship between COVID-19 and inflammatory rheumatic diseases (IRDs). We wanted to assess the role of targeted synthetic or biologic disease-modifying antirheumatic drugs (ts/bDMARDs) and other variables in the development of moderate-severe COVID-19 disease in IRD. Methods: An observational longitudinal study was conducted during the epidemic peak in Madrid (1 March to 15 April 2020). All patients attended at the rheumatology outpatient clinic of a tertiary hospital in Madrid with a medical diagnosis of IRD were included. Main outcome: hospital admission related to COVID-19. Independent variable: ts/bDMARDs. Covariates: sociodemographic, comorbidities, type of IRD diagnosis, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Incidence rate (IR) of hospital admission related to COVID-19 was expressed per 1000 patient-months. Cox multiple regression analysis was run to examine the influence of ts/bDMARDs and other covariates on IR of hospital admission related to COVID-19. Results: A total of 3951 IRD patients were included (5896 patient-months). Methotrexate was the csDMARD most used. Eight hundred and two patients were on ts/bDMARDs, mainly anti-TNF agents, and Rtx. Hospital admissions related to COVID-19 occurred in 54 patients (1.36%) with an IR of 9.15 (95% confidence interval: 7–11.9). In the multivariate analysis, older, male, comorbidities, and specific systemic autoimmune conditions (Sjögren, polychondritis, Raynaud, and mixed connective tissue disease) had more risk of hospital admissions. Exposition to ts/bDMARDs did not achieve statistical significance. Use of glucocorticoids, NSAIDs, and csDMARDs dropped from the final model. Conclusion: This study provides additional evidence in IRD patients regarding susceptibility to moderate–severe infection related to COVID-19.

Current gold-standard strategies for bone regeneration do not achieve the optimal recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells—such as mesenchymal stem cells (MSCs)—and bioactive ceramic scaffolds—such as calcium phosphate-based (CaPs) bioceramics—seem promising. The biological properties of MSCs are influenced by the tissue source. This study aims to define the optimal MSC source and construct (i.e., the MSC–CaP combination) for clinical application in bone regeneration. A previous iTRAQ analysis generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. MSCs were isolated from adipose tissue, bone marrow, and dental pulp, then cultured both on a plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate), to compare their biological features. On plastic, MSCs isolated from dental pulp (DPSCs) presented the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs demonstrated the greatest capacity to colonise the bioceramics. Furthermore, the results demonstrated a trend that DPSCs had the most robust increase in ALP activity. Regarding CaPs, β-tricalcium phosphate obtained the best viability results, while hydroxyapatite had the highest ALP activity values. Therefore, we propose DPSCs as suitable MSCs for cell-based bone regeneration strategies.

Background: Bone innate ability to repair without scaring is surpassed by major bone damage. Current gold-standard strategies do not achieve a full recovery of the bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells, like mesenchymal stem cells (MSCs), and bioactive ceramic scaffolds, like calcium phosphate-based (CaPs), are promising. Biological properties of the MSCs, including osteogenic potential, are influenced by the tissue source. The aim of this study is to define the MSC source and construct (MSC and scaffold combination) most interesting for its clinical application in the context of bone regeneration.Methods: MSCs of 9 healthy donors were isolated from adipose tissue, bone marrow and dental pulp. MSCs were cultured both on plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate) to compare their biological features: proliferation rate, osteogenic potential, cell viability and activity, ability to colonize the CaPs and ALP activity. Results: iTRAQ results generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. On plastic, MSCs isolated from dental pulp (DPSCs) were the MSCs with the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs are the MSCs with the greatest capacity to colonize bioceramics. Furthermore, results show a trend for DPSCs are the MSCs with the most robust increase in the ALP activity.Conclusion: Based in our results, we propose DPSCs as a suitable MSCs for bone/dental regeneration cell-based strategies.

Bone innate ability to repair without scaring is surpassed by major bone damage. Current gold-standard strategies do not achieve a full recovery of bone biomechanical properties. To bypass these limitations, tissue engineering techniques based on hybrid materials made up of osteoprogenitor cells, like mesenchymal stem cells (MSCs), and bioactive ceramic scaffolds, like calcium phosphate-based (CaPs), are promising. Biological properties of the MSCs, are influenced by the tissue source. The aim of this study is to define the MSC source and construct (MSC and scaffold combination) most interesting for its clinical application in bone regeneration. iTRAQ generated the hypothesis that anatomical proximity to bone has a direct effect on MSC phenotype. MSCs were isolated from adipose tissue, bone marrow and dental pulp. MSCs were cultured both on plastic surface and on CaPs (hydroxyapatite and β-tricalcium phosphate) to compare their biological features. On plastic, MSCs isolated from dental pulp (DPSCs) were the MSCs with the highest proliferation capacity and the greatest osteogenic potential. On both CaPs, DPSCs are the MSCs with the greatest capacity to colonize bioceramics. Furthermore, results show a trend for DPSCs are the MSCs with the most robust increase in the ALP activity. We propose DPSCs as a suitable MSCs for bone regeneration cell-based strategies.What do you want to do ?New mailCopy

Background: In this pandemia, it is essential for rheumatologist and patients to know the relationship between COVID-19 and inflammatory rheumatic diseases (IRD). We want to assess the role of targeted synthetic or biologic disease modifying antirheumatic drugs (ts/bDMARDs) and other variables in the development of moderate-severe COVID-19 disease in IRD. Methods: An observational longitudinal study was conducted (1stMar to 15thApr 2020). All patients from the rheumatology outpatient clinic from a hospital in Madrid with a medical diagnosis of IRD were included. Main outcome: hospital admission related to COVID-19. Independent variable: ts/bDMARDs. Covariates: sociodemographic, comorbidities, type of IRD diagnosis, glucocorticoids, NSAIDs and conventional synthetic DMARDs (csDMARDs). Incidence rate (IR) of hospital admission related to COVID-19, was expressed per 1,000 patients-month. Cox multivariate regression analysis was run to examine the influence of ts/bDMARDs and other covariates on IR. Results: 3,591 IRD patients were included (5,896 patients-month). Concerning csDMARDs, methotrexate was the most used followed by antimalarials. 802 patients were on ts/bDMARDs, mainly anti-TNF agents, and rituximab. Hospital admissions related to COVID-19 occurred in 54 patients (1.36%) with an IR of 9.15 [95%CI: 7-11.9]. In the multivariate analysis, older, male gender, presence of comorbidities and specific systemic autoimmune conditions (Sjoegren, polychondritis, Raynaud and mixed connective tissue disease) had more risk of hospital admissions regardless other factors. Exposition to ts/bDMARDs did not achieve statistical signification. Use of glucocorticoids, NSAIDs, and csDMARDs dropped from the final model. Conclusion: This study provides additional evidence in IRD patients regarding susceptibility to moderate-severe infection related to COVID-19.

OBJECTIVES: To describe patients with inflammatory rheumatic diseases (IRD) who had COVID-19; to compare patients who need hospital admission versus those that did not and assess risk factors of hospital admission related to COVID-19. METHODS: We performed a prospective observational study, from 1st March 2020 until the 24th of April. All patients being attended at the rheumatology outpatient clinic of a tertiary hospital of Madrid, with medical diagnosis of inflammatory rheumatic disease, and with symptomatic COVID-19 disease were included. Main variable was the hospital admission related to COVID-19. Covariates: sociodemographic, clinical and treatments. We performed a multivariate logistic regression model to assess risk factors of hospital admission. RESULTS: 123 patients with IRD and COVID-19 disease were identified and included. We found 54 patients that need hospital admission, 59.2% were women, with a mean age at hospital admission of 69.7 (15.7) years, and a median lag time from symptoms onset to hospital admission of 5 (3-10) days. The median length of stay was 9 (6-14) days. A total of 12 patients died (22%) during their hospital admission. Factors independently associated with hospital admission were being older (OR 1.08; p=0.00), and type of diagnosis (OR 3.55; p=0.01), compared to those who were ambulatory. DMARDs dropped from the model. Male sex, associated comorbidities and glucocorticoids use showed a tendency risk (p

We developed and independently validated a rheumatoid arthritis (RA) mortality prediction model using the machine learning method Random Survival Forests (RSF). Two independent cohorts from Madrid (Spain) were used: the Hospital Clínico San Carlos RA Cohort (HCSC-RAC; training; 1,461 patients), and the Hospital Universitario de La Princesa Early Arthritis Register Longitudinal study (PEARL; validation; 280 patients). Demographic and clinical-related variables collected during the first two years after disease diagnosis were used. 148 and 21 patients from HCSC-RAC and PEARL died during a median follow-up time of 4.3 and 5.0 years, respectively. Age at diagnosis, median erythrocyte sedimentation rate, and number of hospital admissions showed the higher predictive capacity. Prediction errors in the training and validation cohorts were 0.187 and 0.233, respectively. A survival tree identified five mortality risk groups using the predicted ensemble mortality. After 1 and 7 years of follow-up, time-dependent specificity and sensitivity in the validation cohort were 0.79–0.80 and 0.43–0.48, respectively, using the cut-off value dividing the two lower risk categories. Calibration curves showed overestimation of the mortality risk in the validation cohort. In conclusion, we were able to develop a clinical prediction model for RA mortality using RSF, providing evidence for further work on external validation.

Background An increased risk of cardiovascular (CV) complications has been described in patients with rheumatoid arthritis (RA). It is the result of the combined effect of classic CV risk factors and others that are specific to the disease. Methods We assessed data from 448 early arthritis (EA) patients: 79% women, age (median [p25-p75]) at onset: 55 [44?67] years and disease duration at study entry 5 [3?8] months; and 72% fulfilled the 1987 RA criteria at 2?years of follow-up. Rheumatoid factor was positive in 54% of patients and anti-citrullinated peptide antibodies in 50%. The follow-up of patients ranged from 2 to 5?years with more than 1400 visits with lipoprotein measurements available (mean 2.5 visits/patient). Demographic- and disease-related variables were systematically recorded. Total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were obtained from routine laboratory tests. Oxidized-LDL (oxLDL-C) levels were assessed using a commercial ELISA kit. We fitted population-averaged models nested by patient and visit to determine the effect of independent variables on serum levels of TC, its fractions, and oxLDL-C. Results After adjustment for several confounders, high-disease activity was significantly associated with decreased TC, HDL-C, and LDL-C levels and increased oxLDL-C levels. Standardized coefficients showed that the effect of disease activity was greater on oxLDL-C and HDL-C. Interestingly, we observed that those patients with lower levels of LDL-C showed higher oxLDL-C/LDL-C ratios. Conclusions High-disease activity in EA patients results in changes in the HDL-C and oxLDL-C levels, which in turn may contribute to the increased risk of CV disease observed in these patients. Our manuscript was supported by grants RD16/0011/0012, RD16/0011/0009, RD16/0011/0004, PI05/2044, and PI18/0371 from the Ministerio de Economía y Competitividad (Instituto de Salud Carlos III) and co-funded by Fondo Europeo de Desarrollo Regional (FEDER).

Resumen Objetivo Estimar los costes medicos directos en los pacientes con artritis reumatoide (AR) y los factores predictores en los pacientes tratados con farmacos biologicos y sin biologicos. Metodos Se realizo un estudio transversal en una muestra incluyendo pacientes de toda la geografia nacional. Se obtuvieron datos sociodemograficos y de tratamiento. Se registro la utilizacion de recursos para los 2 anos de estudio y se hizo imputacion de costes. Se realizaron analisis de correlacion en todos los pacientes con AR y en los tratados con y sin biologicos, para estimar las diferencias entre los grupos. Los predictores de costes se analizaron mediante modelos de regresion lineal. Resultados Se incluyeron 1.095 pacientes con AR, el 26% hombres, con una edad media de 62 ± 14 anos. La media de los costes medicos directos por paciente fue de 24.291 ± 45.382 €. Excluyendo los farmacos biologicos, el coste medio por paciente fue de 3.742 ± 3.711 €. Despues de ajustar, los factores predictores de costes medicos directos para todos los pacientes con AR fueron los farmacos biologicos (p = 0,00), la comorbilidad (p = 0,00) y la edad del paciente (p = 0,01). En el grupo sin biologicos, los predictores fueron la comorbilidad (p = 0,00) y la edad del paciente (p = 0,01). En el grupo con biologicos los predictores fueron el sexo del paciente (p = 0,03) y la actividad de la enfermedad (p = 0,02). Conclusion Los datos muestran un notable impacto economico de la AR. Es importante identificar y estimar los factores asociados a mayor coste para desarrollar estrategias de reduccion de costes y aumentar la calidad de la atencion.

Objective To analyze the resource utilization in rheumatoid arthritis (RA) patients and predictive factors in and patients treated with biological drugs and biologic-naive. Methods A cross-sectional study was performed in a sample including all regions and hospitals throughout the country. Sociodemographic data, disease activity parameters and treatment data were obtained. Resource utilization for two years of study was recorded and we made costs imputation. Correlation analyzes were performed on all RA patients and those treated with biological and biological naive, to estimate the differences in resource utilization. Factors associated with increased resources utilization (costs) attending to treatment was analyzed by linear regression models. Results We included 1.095 RA patients, 26% male, mean age of 62 ± 14 years. Mean of direct medical costs per patient was €24,291 ± €45,382. Excluding biological drugs, the average cost per patient was €3742 ± €3711. After adjustment, factors associated with direct medical costs for all RA patients were biologic drugs (P = .02) and disease activity (P = .004). In the biologic-naive group, the predictor of direct medical costs was comorbidity (P Conclusion Our data show a remarkable economic impact of RA. It is important to identify and estimate the economic impact of the disease, compare data from other geographic samples and to develop improvement strategies to reduce these costs and increase the quality of care.

Purpose: To report the incidence rate (IR) of remission in pediatric noninfectious intermediate uveitis (IU). Methods: Longitudinal retrospective cohort study, including 19 patients (32 eyes) between 1985 and 2014, followed-up until loss or January 2016. Remission was defined following the Standardization of Uveitis Nomenclature workshop criteria, prolonged remission as a remission spanning 12 months and until the end of follow-up, and relapse as recurrence of inflammatory activity in an eye in remission. Results: Median follow-up time was 6.3 years. IRs (95% confidence interval) for remission, relapse, and prolonged remission were 18.6 (13.1–26.5), 32.3 (20.6–50.7), and 6.7 (3.8–11.9) episodes per 100 eye-years, respectively. 48% of eyes relapsed in the first year following remission. 25 and 50% of eyes achieved prolonged remission after 5 and 10 years of follow-up, respectively. Conclusions: Inflammatory relapses may be frequent in noninfectious IU affecting children and adolescents, appearing early after remission. Also, prolonged remission seems infrequent, being achieved late during follow-up.

Introduction We have conducted a bibliometric study of the scientific publications on patient-reported outcomes in the field of rheumatology. Methods SCOPUS was the database used in this bibliometric study. We performed two searches. The main search involved selecting the documents published between 2000 and 2014 limited to top-tier journals addressing rheumatic and musculoskeletal diseases, using specific descriptors together with the operator and main descriptor "patient-reported outcomes" (PROs), and we performed a secondary search, with the following specific descriptors: "pain," "functional capacity," and "fatigue." We used bibliometric indicators for articles distribution (Price's law for the increase of scientific literature and Bradford's law for dispersion of articles). We also calculated the participation index of the different countries. Results A total of 983 original articles were published between 2000 and 2014. Our results confirmed the fulfilment of Price's law (correlation coefficient r = 0.9385 after linear adjustment). The average number of articles per Bradford Zone was 327.6. A total of 30 different journals were published. The type of growth for the descriptors "pain" ( r 2 = 0.5417 compared to r 2 = 0.4839) and "fatigue" ( r 2 = 06276 compared to r 2 = 0.5544) is exponential, whereas it is linear for the descriptor "functional capacity" ( r 2 = 0.6769 compared to r 2 = 0.3779). Discussion This study revealed significant linear growth of patient-related outcomes in global terms, as well as upward trends for most of the citation-based bibliometric indices, especially significant from 2010 to 2014. Pain and fatigue have greater growth as PRO concepts.

The health of the global population has undergone rapid transformation. Life expectancy and chronic conditions are increasing, and persons aged 65 years or older have become the fastest growing segment of population. The worldwide picture of disease burden is increasingly defined by disability instead of premature mortality. Population growth, ageing and sedentary lifestyles, particularly in developing countries, will result in a crisis for the population health that requires a multi-system response. The growing awareness of the diseases burden increases the need for accurate measurement and assessment of the burden and measurement of the impact of any public health action. Musculoskeletal (MSK) diseases are increasingly recognised as a major and important group of diseases, which requires more attention from society and health care systems. The epidemiological evidence confirms the dramatic increase in the majority of MSK disorders with age, a phenomenon that is occurring in all parts of the world, particularly among females. There is a necessity to ensure global health policies to recognise the importance of disability burden for overall health, well-being and economic prosperity for the individual and society. It is important to promote a common goal between public health, primary care, specialised health and social services to reduce disability; to encourage health programs or models of care addressing chronic conditions, including the importance of primary and secondary prevention, early intervention, care coordination, access to a multidisciplinary team to address the bio-psychosocial aspects of chronic conditions. There is an identified need to develop a Health Care Systems response to enable the implementation of early intervention as an effective strategy to reduce the burden of MSK disorders with particular importance and potential gains for the target population of older people who have shown an acute loss of function due to MSK diseases. It will contribute to meeting the ‘triple aim' goals in health systems of improving patient's care experience (satisfaction, confidence and trust), improving the health of people and populations (mortality, disability and quality of life) and improving the societal costs of diseases.

Background:Musculoskeletal diseases (MSKs) are the major cause of disability, affecting the patient’s daily activities as well as their Quality of Life (QoL).Objectives:To analyze in a cohort of patients with MSKs the influence of demographic and clinical predictors in repeated measures of Health-Related QoL (HRQoL) obtained from a departmental electronic health record (EHR)Methods:Patients attending the Hospital Clínico San Carlos rheumatology outpatient clinic (HCSC-MSK cohort) from April 1st, 2007 to November 30th, 2017 who were seen at least twice were included in this study. Visits separated more than one year from previous or next visit were excluded. Our primary outcome was HRQoL collected in each patient’s visit using the Rosser Classification Index (it ranges between 0 and 1, the higher value, the higher HRQoL. It is calculated as the combination of two subscales: disability and distress). Demographic and clinical variables, such as diagnoses, treatments, and comorbidities were included as predictors. Variable selection was carried out in 4 steps. First, we developed a bivariate Generalized Estimating Equations model, selecting those variables with a p-value < 0.15. Second, those with a pair-wise absolute correlation < 0.95 were carried to the next step. Third, multivariate GEE analyses were performed including clinical related variables, and those independently associated with our primary outcome were selected with a p-value < 0.15. At least one predictor of each multivariate analyses was included even if none of them had p-value < 0.15. In this case the one, with the lowest p-value was chosen. Fourth, a grid search approach was followed to determine the penalization value and a penalized GEE model was implemented including all selected variables and using an independence correlation structure. Those with an estimate greater than 10^-3 and a z-robust > 1.96 were considered to be independently associated with the HRQoL.Results:A total of 18,187 patients with 95,960 outpatient visits were included in this study. From the initial 410 predictors, 289, 241, 153, and 34 were selected in the first, second, third, fourth and fifth steps. The median age was 56.4 years. The major part of the patients were women (69.4%), and the medianRosservalue was 0.986. More common diagnoses, treatments and comorbidities were back pain, tendinitis, pain in joint; analgesia, gastric protector and NSAIDs; hypertension, dyslipidemia and diabetes respectively. The predictors with a greater negative impact in HRQoL were the use of 3rd level analgesics and azathioprine, a presence of kidney failure, fibromyalgia, and ischemic heart disease. Conversely, use of symptomatic slow action drugs for osteoarthritis, statins, lowering uric acid drugs, a diagnose of mixed connective tissue disease, and better HRQoL in the past six months were independently associated with a positive impact in the HRQoL.Conclusion:We have identified several diagnoses, treatments and comorbidites independently associated with HRQoL in a cohort of patients followed up in a rheumatology outpatient clinic. This represent a first step in the implementation of value-based care for MSK patients, as we can now review the procedures associated with a worse HRQoL in an attempt to improve them.References:Predictor selection. Dx: Diagnoses. DxE: Diagnoses Episode. DxTFT: Diagnoses Total Follow-up Time.DxTET: Diagnoses Total Episode Follow-up Time T: Treatment. DxE: Treatment Episode. DxTFT:Treatment Total Follow-up Time. DxTET: Treatment Total Episode Follow-up Time. XM: Comorbiditiesand Concomitant Treatments. DM: Demographics. HS: Health Status.Disclosure of Interests:None declared