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1.
Immunotherapy ; 11(13): 1107-1116, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31378114

RESUMO

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.

2.
Trials ; 20(1): 387, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262366

RESUMO

PURPOSE: The purpose of the study was to compare the safety and efficacy of autologous mesenchymal stem cells (MSCs) embedded in a xenogenic scaffold for repairing the supraspinatus tendon. METHODS: This was a randomized, double-blind and placebo-controlled trial evaluating patients with full-thickness rotator cuff tears (Eudra-CT, 2007-007630-19). Effectiveness was evaluated using the Constant score and a visual analogue pain scale (VAS). Constant score has four domains including pain (15 possible points), activities of daily living (20 possible points), mobility (40 possible points), and strength (25 possible points). Scores range from 0 points (most disability) to 100 points (least disability). The structural integrity of the repaired tendon was assessed by magnetic resonance imaging (MRI) according to Patte and Thomazeau classification criteria. The primary study end point was an improvement in the Constant score by 20 points at one year compared to initial assessment. RESULTS: The trial was stopped due to adverse effects observed in both groups. Only thirteen patients were included and analyzed. The Constant questionnaire showed a significant improvement in the MSC treatment group compared with the preoperative data (p = 0.0073). Secondary outcome measures were similar in both groups. CONCLUSIONS: Our study showed preliminary inconclusive clinical outcomes in the patients treated with MSCs. Adverse events revealed the need for further approaches using scaffolds of a different nature or perhaps no scaffolds, in the context of small joints. TRIAL REGISTRATION: Eudra-CT, 2007-007630-19 . Registered on 30 January 2008. LEVEL OF EVIDENCE: A Level 1 of evidence treatment study.

3.
Front Immunol ; 10: 1459, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312201

RESUMO

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

4.
Arthritis Res Ther ; 21(1): 112, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060598

RESUMO

INTRODUCTION: Mesenchymal stem cells (MSCs) have the ability to differentiate into different types of cells of the mesenchymal lineage, such as osteocytes, chondrocytes, and adipocytes. It is also known that under inflammatory stimuli or in the appropriate experimental conditions, they can also act as regulators of inflammation. Thus, in addition to their regenerating potential, their interest has been extended to their possible use in cell therapy strategies for treatment of immune disorders. OBJECTIVE: To analyze, by RNA-seq analysis, the transcriptome profiling of allogenic MSCs under RA lymphocyte activation. METHODS: We identified the differentially expressed genes in bone marrow mesenchymal stem cells after exposure to an inflammatory environment. The transcriptome profiling was evaluated by means of the precise measurement of transcripts provided by the RNA-Seq technology. RESULTS: Our results evidenced the existence of blocking of both regenerative (differentiation) and immunomodulatory phenotypes under inflammatory conditions characterized by an upregulation of genes involved in immune processes and a simultaneous downregulation of genes mainly involved in regenerative or cell differentiation functions. CONCLUSIONS: We conclude that the two main functions of MSCs (immunomodulation and differentiation) are blocked, at least while the inflammation is being resolved. Inflammation, at least partially mediated by gamma-interferon, drives MSCs to a cellular distress adopting a defensive state. This knowledge could be of particular interest in cases where the damage to be repaired has an important immune-mediated component.

5.
Clin Exp Rheumatol ; 37(5): 774-782, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30789151

RESUMO

OBJECTIVES: Cardiovascular (CV) disease is one of the main causes of morbi-mortality in spondyloarthritis (SpA), partially explained by traditional CV risk factors. Information on lipoprotein(a) [Lp(a)], a non-conventional risk factor, in SpA is scarce. In this study we assessed the prevalence of hyperlipoproteinaemia(a) in SpA patients and analysed the possible related factors. METHODS: A baseline analysis was made of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) patients and controls included in the CARMA project (CARdiovascular in RheuMAtology), a 10-year prospective study evaluating the risk of CV events in chronic inflammatory rheumatic diseases. A multivariate logistic regression model was performed using hyperlipoproteinaemia(a) (Lp(a) >50 mg/dl) as a dependent variable and adjusting for confounding factors. RESULTS: 19.2% (95% CI: 16.80-22.05) of the SpA patients [20.7% (95% CI: 16.91-24.82) of those with AS and 17.7% (95% CI: 14.15-21.75) of those with PsA] and 16.7% (95% CI: 13.23-20.86) of the controls had hyperlipoproteinaemia(a) (p=0.326). Adjusting for age and sex, SpA patients were more likely to have hyperlipoproteinaemia(a) than controls (OR: 1.43, 95%CI: 1.00-2.04; p=0.05), especially those with AS (OR: 1.81, 95%CI: 1.18-2.77; p=0.007). In the adjusted model, apolipoprotein B in all patients, non-steroidal anti-inflammatory drugs in AS, and female sex in PsA, were associated with hyperlipoproteinaemia(a). No disease-specific factors associated with hyperlipoproteinaemia(a) were identified. CONCLUSIONS: SpA patients show a moderately increased risk of hyperlipoproteinaemia(a) compared to controls, especially those with AS. Lp(a) determination may be of interest to improve the CV risk assessment in SpA patients.


Assuntos
Hiperlipoproteinemias , Espondilartrite , Artrite Psoriásica , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Hiperlipoproteinemias/epidemiologia , Masculino , Estudos Prospectivos , Fatores de Risco , Espondilartrite/sangue , Espondilartrite/epidemiologia
8.
Ann Rheum Dis ; 78(3)2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30552173

RESUMO

OBJECTIVE: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis affecting up to 30% of patients with psoriasis (Ps). To date, most of the known risk loci for PsA are shared with Ps, and identifying disease-specific variation has proven very challenging. The objective of the present study was to identify genetic variation specific for PsA. METHODS: We performed a genome-wide association study in a cohort of 835 patients with PsA and 1558 controls from Spain. Genetic association was tested at the single marker level and at the pathway level. Meta-analysis was performed with a case-control cohort of 2847 individuals from North America. To confirm the specificity of the genetic associations with PsA, we tested the associated variation using a purely cutaneous psoriasis cohort (PsC, n=614) and a rheumatoid arthritis cohort (RA, n=1191). Using network and drug-repurposing analyses, we further investigated the potential of the PsA-specific associations to guide the development of new drugs in PsA. RESULTS: We identified a new PsA risk single-nucleotide polymorphism at B3GNT2 locus (p=1.10e-08). At the pathway level, we found 14 genetic pathways significantly associated with PsA (pFDR<0.05). From these, the glycosaminoglycan (GAG) metabolism pathway was confirmed to be disease-specific after comparing the PsA cohort with the cohorts of patients with PsC and RA. Finally, we identified candidate drug targets in the GAG metabolism pathway as well as new PsA indications for approved drugs. CONCLUSION: These findings provide insights into the biological mechanisms that are specific for PsA and could contribute to develop more effective therapies.

9.
Clin Rheumatol ; 38(5): 1329-1337, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30588556

RESUMO

BACKGROUND: Atherosclerosis leading to cardiovascular disease (CVD) is the main cause of mortality and morbidity in patients with rheumatoid arthritis (RA). Paraoxonase1 (PON1) is the best understood member of plasma paraoxonases with anti-atherogenic properties. PATIENTS AND METHODS: Spanish RA (n = 549) consecutively recruited from 1 single center and 477 ethnically matched healthy controls were included in a case-control study. The concentration of PON1 was evaluated by means of an enzyme-linked immunosorbent sssay (ELISA). An arylesterase/paraoxonase assay kit was used to evaluate PON1 activity. Sample genotyping was performed by using TaqMan assays-on-demand. All results were expressed as medians ± interquartile range. One-way ANOVA comparisons were done using a nonparametric Kruskall-Wallis test. P values under 0.05 were considered to be significant. RESULTS: The concentration of PON1 in the RA group was higher than in control group (p = 0.0003), although the differences were not significant when PON1 activities were compared between both groups. No significant differences were found related to distributions of rs662 genotypes in RA patients compared to healthy controls. Among rs854860 polymorphisms, overall genotype was widely distributed between RA patients and controls. Overall PON1 concentration in plasma was not significantly different between individuals carrying any of rs662 (p = 0.8501) or rs854860 (p = 0.2741) polymorphisms. Although PON1 levels were not associated with any of the SNPs in the study, differences appear when enzyme activities are compared for each SNP separately. CVD in RA patients correlate with increased PON1 levels and lower PON1 activity. CONCLUSIONS: Although protective role of PON1 against oxidative damage in vivo could be related to other activities, in our study arylesterase activity was useful to identify phenotypic differences with emphasis placed on two SNPs coding for nonconservative amino acid changes in the functional protein.

10.
Clin Rheumatol ; 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30328025

RESUMO

The study aims to analyze the association between the bone and cartilage/periarticular components of the radiographic joint damage and disability over the course of disease, in a cohort of rheumatoid arthritis (RA) patients from a day-to-day clinical practice. The secondary aim is to study the role of demographic and disease-related variables in this association. We performed a retrospective longitudinal study including 736 RA patients. Disability was assessed with the health assessment questionnaire (HAQ), and radiographic joint damage of hands and wrists with the Sharp van-der-Heijde score (total (SHS), erosion (ES), and narrowing/(sub)luxation (NSLS) components]. Generalized estimating equations models, adjusted by disease activity, demographic and disease-related variables, were used to test the relationship between SHS and medium-term (median value of the HAQs performed in the following year after each radiograph) and long-term (set of HAQ measures performed during follow-up, at least 1 year apart from the first x-ray) disability. Interaction terms between the SHS and demographic and disease-related variables were introduced in the models. To account for multiple testing, Bonferroni correction was applied. NSLS was independently associated with medium-term disability, even after Bonferroni correction. We observed significant and positive interactions between NSLS and age at x-ray, and with the ES. SHS showed no association with long-term disability. The cartilage/soft tissue component of the radiographic joint damage seems to exert a much more important role in medium-term disability than the erosive component. This association could be modulated by the age at the x-ray and by the magnitude of the erosive damage.

11.
Arthritis Rheumatol ; 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30277011

RESUMO

OBJECTIVES: The new RA-specific autoantibodies, the anti-carbamylated protein antibodies (ACarPA), provide an opportunity to improve management and understanding of RA. However, many questions remain about them, including their relationship with HLA-DRB1 alleles. MATERIAL AND METHODS: The samples of 1126 RA patients from three collections were obtained. Serum reactivity against in vitro carbamylated FCS proteins was determined by ELISA. HLA-DRB1 alleles were determined by either hybridization techniques or imputation from HLA dense genotypes. These results were combined by meta-analysis with data from three previously reported cohorts. The carrier frequencies of the common HLA-DRB1 alleles were compared between the antibody-positive subgroups and the double-negative subgroup in ACPA/ACarPA stratified patients, and between the four patient strata and the healthy controls. RESULTS: Meta-analysis was conducted with 3709 RA patients and 2305 healthy subjects. It revealed a significant increase of HLA-DRB1*03 carriers in the ACPA- /ACarPA+ subgroup in comparison with both ACPA- /ACarPA- patients and healthy controls that was consistent in the six sample collections. This association was independent of the SE and the analyzed confounders. No other allele was specifically associated with ACPA- /ACarPA+ patients. In contrast, the SE was significantly increased in the ACPA+ /ACarPA- and ACPA+ /ACarPA+ patient subgroups without distinction between them. Also, some alleles (including HLA-DRB1*03) were associated with protection from ACPA+ RA. CONCLUSION: A specific association of HLA-DRB1*03 with ACPA- /ACarPA+ RA has been identified that suggests preferential presentation of carbamylated peptides as a new mechanism for HLA contribution to RA susceptibility. This article is protected by copyright. All rights reserved.

12.
Arthritis Rheumatol ; 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30251476

RESUMO

OBJECTIVE: A genome-wide association study (GWAS) was conducted to shed light into the genetic background influencing the development of cardiovascular (CV) disease in patients diagnosed with rheumatoid arthritis (RA). METHODS: After quality control and imputation, a total of 6,308,944 polymorphisms across the whole genome were analysed in 2,989 RA patients from European origin. Data on subclinical atherosclerosis, obtained by carotid ultrasonography through assessment of carotid intima-media thickness (cIMT) and presence/absence of carotid plaques, were available for 1,355 individuals. RESULTS: A genetic variant of the RARB gene (rs116199914) was associated with cIMT values at the genome-wide level of significance (minor allele (G): beta (ß) coefficient=0.142, P=1.86E-08). Interestingly, rs116199914 overlapped with regulatory elements in tissues related to CV pathophysiology and immune cells. In addition, biological pathway enrichment and predictive protein-protein relationship analyses, including suggestive GWAS signals of potential relevance, revealed a functional enrichment of the collagen biosynthesis network related to the presence/absence of carotid plaques (GO:0032964, PFDR =4.01E-03). Furthermore, our data suggest a potential influence of the previously described candidate CV risk loci NFKB1, MSRA and ZC3HC1 (P=8.12E-04, P=5.94E-04 and P=2.46E-04, respectively). CONCLUSION: Our study strongly suggests that genetic variation within RARB contributes to the development of subclinical atherosclerosis in patients with RA. This article is protected by copyright. All rights reserved.

13.
Sci Rep ; 8(1): 8195, 2018 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-29844438

RESUMO

A rare variant (BAFF-var) of the tumor necrosis factor superfamily 13b (TNFSF13B) gene has been recently associated with multiple sclerosis (MS) and systemic lupus erythematosus (SLE). The aim of this study was to investigate the association between TNFSF13B BAFF-var and susceptibility to rheumatoid arthritis (RA) and replicate that association in SLE. 6,218 RA patients, 2,575 SLE patients and 4,403 healthy controls from three different countries were included in the study. TNFSF13B BAFF-var was genotyped using TaqMan allelic discrimination assay. PLINK software was used for statistical analyses. TNFSF13B BAFF-var was significantly associated with RA (p = 0.015, OR = 1.21, 95% CI = 1.03-1.41) in the Spanish cohort. A trend of association was observed in the Dutch (p = 0.115) and German (p = 0.228) RA cohorts. A meta-analysis of the three RA cohorts included in this study revealed a statistically significant association (p = 0.002, OR = 1.24, 95% CI = 1.10-1.38). In addition, TNFSF13B BAFF-var was significantly associated with SLE in the Spanish (p = 0.001, OR = 1.41, 95% CI = 1.14-1.74) and the German cohorts (p = 0.030, OR = 1.86, 95% CI = 1.05-3.28), with a statistically significant p-value obtained in the meta-analysis (p = 0.0002, OR = 1.46, 95% CI = 1.09-2.32). The results obtained confirm the known association of TNFSF13B BAFF-var with SLE and, for the first time, demonstrate that this variant contributes to susceptibility to RA.

14.
Reumatol. clín. (Barc.) ; 14(1): 4-8, ene.-feb. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-170366

RESUMO

Objetivo. Estimar los costes médicos directos en los pacientes con artritis reumatoide (AR) y los factores predictores en los pacientes tratados con fármacos biológicos y sin biológicos. Métodos. Se realizó un estudio transversal en una muestra incluyendo pacientes de toda la geografía nacional. Se obtuvieron datos sociodemográficos y de tratamiento. Se registró la utilización de recursos para los 2 años de estudio y se hizo imputación de costes. Se realizaron análisis de correlación en todos los pacientes con AR y en los tratados con y sin biológicos, para estimar las diferencias entre los grupos. Los predictores de costes se analizaron mediante modelos de regresión lineal. Resultados. Se incluyeron 1.095 pacientes con AR, el 26% hombres, con una edad media de 62±14 años. La media de los costes médicos directos por paciente fue de 24.291±45.382€. Excluyendo los fármacos biológicos, el coste medio por paciente fue de 3.742±3.711€. Después de ajustar, los factores predictores de costes médicos directos para todos los pacientes con AR fueron los fármacos biológicos (p=0,00), la comorbilidad (p=0,00) y la edad del paciente (p=0,01). En el grupo sin biológicos, los predictores fueron la comorbilidad (p=0,00) y la edad del paciente (p=0,01). En el grupo con biológicos los predictores fueron el sexo del paciente (p=0,03) y la actividad de la enfermedad (p=0,02). Conclusión. Los datos muestran un notable impacto económico de la AR. Es importante identificar y estimar los factores asociados a mayor coste para desarrollar estrategias de reducción de costes y aumentar la calidad de la atención (AU)


Objective. To analyze the resource utilization in rheumatoid arthritis (RA) patients and predictive factors in and patients treated with biological drugs and biologic-naïve. 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 naïve, 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 €3,742±€3,711. 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-naïve group, the predictor of direct medical costs was comorbidity (P<.001). In the biologic treatment group predictors were follow-up length of the disease (P=.04), age (P=.02) and disease activity (P=.007). 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 (AU)


Assuntos
Humanos , Artrite Reumatoide/epidemiologia , Espondilartrite/epidemiologia , Custos Diretos de Serviços/estatística & dados numéricos , Estudos Transversais , Indicadores Econômicos , Recursos em Saúde/organização & administração
15.
Clin Exp Rheumatol ; 36 Suppl 111(2): 121-128, 2018 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29303708

RESUMO

OBJECTIVES: To assess the incidence and the risk of relapses in giant cell arteritis (GCA) patients treated with and without methotrexate (MTX) in clinical practice. Other associated factors were also investigated. METHODS: An inception cohort of GCA was assembled in the out-patient clinic at Hospital Clínico San Carlos, including patients from the date of diagnosis (Jan-1991 until Sept-2013), and followed-up until lost of follow up or Sept-2014. MAIN OUTCOME: relapse defined as recurrence of symptoms or signs of GCA with high ESR and the need to increase glucocorticoids at least 10mg over the previous dose. The independent variable was exposure to MTX over time. Covariables: Sociodemographic, clinical, and treatment. Incidence rates of relapses (IR) per 100 patient-year with their 95% confidence intervals [CI] were estimated using survival techniques. MTX influence on relapses was analysed by Cox models. RESULTS: 168 patients were included (675 patient-year). 31% of patients had relapses (IR of 12 [9.6-14.9]), and the median number of relapses was 1[1-2]. 65% of the patients were on MTX, (mean dose: 10mg). In the bivariate analysis, the risk of relapses in patients with and without MTX did not achieve statistical signification (p=0.1). After adjusting in the multivariate analysis, exposure to MTX had 72% less risk of relapse compared to those without MTX (p<0.05). Other variables included in the final model were: visual alterations and malaise at clinical presentation of GCA. CONCLUSIONS: The use of MTX seems to decrease the risk of recurrences. We also found other factors influencing on relapses.


Assuntos
Antirreumáticos/uso terapêutico , Arterite de Células Gigantes/tratamento farmacológico , Metotrexato/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Sedimentação Sanguínea , Quimioterapia Combinada , Feminino , Arterite de Células Gigantes/sangue , Glucocorticoides/administração & dosagem , Humanos , Incidência , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Recidiva , Risco
16.
Ophthalmologica ; 239(2-3): 151-158, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29241207

RESUMO

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.


Assuntos
Uveíte Intermediária/epidemiologia , Acuidade Visual , Adolescente , Criança , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Morbidade/tendências , Recidiva , Remissão Espontânea , Estudos Retrospectivos , Fatores de Risco , Espanha/epidemiologia , Análise de Sobrevida , Fatores de Tempo , Uveíte Intermediária/diagnóstico , Uveíte Intermediária/fisiopatologia
17.
Ocul Immunol Inflamm ; 26(5): 717-725, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28323495

RESUMO

PURPOSE: To analyze the influence of socio-demographic, comorbidity, and clinical-related variables in the vision-related quality of life (VR-QoL) of non-infectious uveitis patients. METHODS: Cross-sectional study includes 156 consecutive non-infectious uveitis patients from a tertiary uveitis clinic from Madrid (Spain). The main outcome was the log-transformed composite score of the Visual Functioning Questionnaire 25. Bivariate and multivariate ordinary least-squares regression models were performed and results expressed using effect sizes with 95% confidence intervals (95% CI). RESULTS: In the multivariate analysis, one unit increase in the logarithm of the minimum angle of resolution scale [i.e., worse best corrected visual acuity (BCVA)] was associated with a seven times worse VR-QoL (a 0.14-fold change [95% CI: 0.07-0.27]). Patients with ocular comorbidities had a 64% worse VR-QoL (a 0.61-fold change [95% CI: 0.49-0.77]). CONCLUSIONS: Lower BCVA and the presence of ocular comorbidities had a significant, independent, and deleterious effect in the VR-QoL of non-infectious uveitis patients.


Assuntos
Nível de Saúde , Qualidade de Vida , Uveíte/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Espanha/epidemiologia , Inquéritos e Questionários , Uveíte/epidemiologia , Uveíte/fisiopatologia , Acuidade Visual , Adulto Jovem
18.
Reumatol Clin ; 14(1): 4-8, 2018 Jan - Feb.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27810462

RESUMO

OBJECTIVE: To analyze the resource utilization in rheumatoid arthritis (RA) patients and predictive factors in and patients treated with biological drugs and biologic-naïve. 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 naïve, 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 €3,742±€3,711. 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-naïve group, the predictor of direct medical costs was comorbidity (P<.001). In the biologic treatment group predictors were follow-up length of the disease (P=.04), age (P=.02) and disease activity (P=.007). 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.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Fatores Biológicos/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Padrões de Prática Médica/economia , Espondilartrite/tratamento farmacológico , Adulto , Idoso , Artrite Reumatoide/economia , Fatores Biológicos/uso terapêutico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Estudos Retrospectivos , Espanha , Espondilartrite/economia
19.
Reumatol Clin ; 2017 Nov 25.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29183710

RESUMO

OBJECTIVE: To determine the reality of the resources and care needs in Spain for the management of patients with osteoarthritis. MATERIALS AND METHOD: An online survey. RESULTS: Description of 190 responses to a structured questionnaire (141 orthopedic surgeons and 49 rheumatologists). CONCLUSIONS: Osteoarthritis has yet to receive appropriate medical attention and a patient management model.

20.
PLoS One ; 12(10): e0185889, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28982122

RESUMO

Autoimmune diseases have a higher prevalence of cardiovascular events compared to the general population. The objective of this study was to investigate the genetic basis of cardiovascular disease (CVD) risk in autoimmunity. We analyzed genome-wide genotyping data from 6,485 patients from six autoimmune diseases that are associated with a high socio-economic impact. First, for each disease, we tested the association of established CVD risk loci. Second, we analyzed the association of autoimmune disease susceptibility loci with CVD. Finally, to identify genetic patterns associated with CVD risk, we applied the cross-phenotype meta-analysis approach (CPMA) on the genome-wide data. A total of 17 established CVD risk loci were significantly associated with CVD in the autoimmune patient cohorts. From these, four loci were found to have significantly different genetic effects across autoimmune diseases. Six autoimmune susceptibility loci were also found to be associated with CVD risk. Genome-wide CPMA analysis identified 10 genetic clusters strongly associated with CVD risk across all autoimmune diseases. Two of these clusters are highly enriched in pathways previously associated with autoimmune disease etiology (TNFα and IFNγ cytokine pathways). The results of this study support the presence of specific genetic variation associated with the increase of CVD risk observed in autoimmunity.


Assuntos
Doenças Autoimunes/complicações , Doenças Cardiovasculares/etiologia , Predisposição Genética para Doença , Variação Genética , Doenças Cardiovasculares/genética , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
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