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1.
BMC Musculoskelet Disord ; 22(1): 792, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34525992

RESUMO

BACKGROUND: Persistent monoarthritis in otherwise well-controlled rheumatoid arthritis presents a therapeutic challenge. Intra-articular (IA) steroids are a mainstay of treatment, though some have queried whether IA disease modifying anti-rheumatic drugs (DMARD) and biologics can be used in those who fail steroid injections. METHODS: A systematic literature review was conducted using four medical databases to identify randomized, controlled trials assessing IA therapies in RA patients. Included studies underwent Cochrane Risk of Bias 2 assessment for quality. RESULTS: Twelve studies were included, 6 of which examined intra-articular (IA) TNF inhibitors (TNFi), and 6 studies evaluating IA methotrexate. Of those evaluating IA TNFi, one study reported statistical improvement in TNFi therapy when compared with placebo. The remaining 5 studies compared IA TNFi therapy with steroid injections. IA TNFi had statistically improved symptom scores and clinical assessments comparable with IA steroid treatments. In the 6 studies evaluating IA methotrexate, the addition of methotrexate to steroid intra-articular therapy was not found to be beneficial, and singular methotrexate injection was not superior to the control arms (saline or triamcinolone). Risk-of-bias (ROB) assessment with the Revised Cochrane ROB tool indicated that 2 of 6 TNFi studies were at some risk or high risk for bias, compared with 5 out of 6 methotrexate studies. CONCLUSION: For persistent monoarthritis in rheumatoid arthritis, IA methotrexate was not found to have clinical utility. Intra-articular TNFi therapy appears to have equal efficacy to IA steroids, though the optimal dose and frequency of injections is yet unknown.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Humanos , Metotrexato/uso terapêutico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
2.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445645

RESUMO

Endogenous DNA derived from the nuclei or mitochondria is released into the bloodstream following cell damage or death. Extracellular DNA, called cell-free DNA (cfDNA), is associated with various pathological conditions. Recently, multiple aspects of cfDNA have been assessed, including cfDNA levels, integrity, methylation, and mutations. Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis, and treatment of RA has highly varied outcomes. cfDNA in patients with RA is elevated in peripheral blood and synovial fluid and is associated with disease activity. Profiling of cfDNA in patients with RA may then be utilized in various aspects of clinical practice, such as the prediction of prognosis and treatment responses; monitoring disease state; and as a diagnostic marker. In this review, we discuss cfDNA in patients with RA, particularly the sources of cfDNA and the correlation of cfDNA with RA pathogenesis. We also highlight the potential of analyzing cfDNA profiles to guide individualized treatment approaches for RA.


Assuntos
Artrite Reumatoide/diagnóstico , Ácidos Nucleicos Livres/análise , Ácidos Nucleicos Livres/genética , Líquido Sinovial/química , Animais , Artrite Reumatoide/genética , Humanos , Prognóstico
3.
Ned Tijdschr Geneeskd ; 1652021 06 24.
Artigo em Holandês | MEDLINE | ID: mdl-34346619

RESUMO

Systemic autoimmune diseases are characterized by their heterogenic clinical presentations and often poorly understood pathogenesis. As such, the diagnosis process may be complex and the final diagnosis is made by an expert, after considering a differential diagnosis. Classification criteria are developed for research purposes to select homogenous populations of already diagnosed patients. In clinical practice, these classification criteria are sometimes misused as diagnostic criteria. We describe three patient histories. Two patients met the classification criteria of several separate diseases, emphasizing the amount of overlap between different sets of criteria and the necessity of making a diagnosis before using classification criteria. A third patient was diagnosed with systemic sclerosis and later developed rheumatoid arthritis; a diagnosis that could have been overlooked if classification criteria were used diagnostically. We describe the correct use of classification criteria in systemic autoimmune diseases and discuss what the diagnostic process is supposed to entail.


Assuntos
Artrite Reumatoide , Doenças Autoimunes , Artrite Reumatoide/diagnóstico , Doenças Autoimunes/diagnóstico , Diagnóstico Diferencial , Humanos
4.
Pan Afr Med J ; 38: 379, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34367458

RESUMO

Introduction: rheumatoid arthritis (RA) dramatically affects the quality of life of patients. The objective of our study was to study the link between the activity of the disease and the quality of life of Guinean (Conakry) and Cameroonian patients with RA. Methods: pilot multicentric cross-sectional study (Ignace Dean National Hospital of Conakry in Guinea and Efoulan Yaoundé District Hospital in Cameroon) for 15 months (1st October 2016 to 30th January 2018). The diagnosis of RA was based on the criteria of the ACR/EULAR. Disease activity was assessed by DAS 28. The EMIR questionnaire and the Steinbrocker score were used to assess quality of life. Results: fifty-two patients, 82% of whom were women. The total EMIR score was 5.06±0.50 as a relatively impaired quality of life. Alteration of quality of life was more marked on psychic components (6.78±0.99) and pain (5.37±0.99). The work component was the least affected (4.03±0.98). DAS28 was significantly related to psychic components (p=0.036, R=0.29), pain (p=0.076, R=0.25), physical (p=0.0029, R=0.41), and at the overall quality of life (total EMIR) (p=0.027, R=0.31). Conclusion: the most significant of RA on quality of life was related to pain (EVA-pain) and RA activity (DAS 28). The results of this pilot study will have to be confirmed by a largest study.


Assuntos
Artrite Reumatoide/fisiopatologia , Dor/etiologia , Qualidade de Vida , Adulto , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/psicologia , Camarões , Estudos Transversais , Feminino , Guiné , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Índice de Gravidade de Doença , Inquéritos e Questionários
5.
S D Med ; 74(8): 363-366, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34461001

RESUMO

Methotrexate therapy has evolved over the years to become a fundamental component in the management of rheumatoid arthritis and psoriasis. Liver toxicity remains an ever-present concern when prescribing methotrexate. As such, methotrexate liver toxicity monitoring guidelines have been developed independently by rheumatologists and dermatologists. The main differentiating factor between the dermatology and rheumatology guidelines is risk stratification. Dermatology guidelines are largely based off of the presence or absence of hepatoxicity risk factors (alcohol usage, obesity, type II diabetes, among other) while the rheumatology guidelines do not emphasize this distinction. Thus, the aim of this review is to identify why these screening guidelines differences exist and discuss if the differences in stratification and screening are valid. We will also briefly examine alternatives to the current gold standard hepatoxicity screening test: the liver biopsy.


Assuntos
Artrite Reumatoide , Doença Hepática Induzida por Substâncias e Drogas , Diabetes Mellitus Tipo 2 , Psoríase , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Consenso , Humanos , Metotrexato/efeitos adversos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico
6.
BMC Musculoskelet Disord ; 22(1): 746, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34461875

RESUMO

BACKGROUND: Shifts in treatment strategies for rheumatoid arthritis (RA) have made ambulatory care more labour-intensive. These developments have prompted innovative care models, including mobile health (mHealth) applications. This study aimed to explore the perceptions of mHealth-inexperienced stakeholders concerning these applications in RA care. METHODS: We performed a qualitative study by focus group interviews of stakeholders including RA patients, nurses specialised in RA care and rheumatologists. The qualitative analysis guide of Leuven (QUAGOL), which is based on grounded theory principles, was used to thematically analyse the data. In addition, the Persuasive Systems Design (PSD) model was used to structure recommended app-features. RESULTS: In total, 2 focus groups with nurses (total n = 16), 2 with patients (n = 17) and 2 with rheumatologists (n = 25) took place. Six overarching themes emerged from the analysis. Efficiency of care and enabling patient empowerment were the two themes considered as expected benefits of mHealth-use in practice by the stakeholders. In contrast, 4 themes emerged as possible barriers of mHealth-use: the burden of chronic app-use, motivational aspects, target group aspects, and legal and organisational requirements. Additionally, recommendations for an ideal mHealth-app could be structured into 4 domains (Primary Task Support, Dialogue Support, Social Support and System Credibility) according to the PSD-framework. Most recommended features were related to improving ease of use (Task Support) and System Credibility. CONCLUSIONS: Although mHealth-apps were expected to improve care efficiency and stimulate patient empowerment, stakeholders were concerned that mHealth-app use could reinforce negative illness behaviour. For mHealth-apps to be successful in practice, challenges according to stakeholders were avoiding long-term poor compliance, finding the target audience and tailoring a legal and organisational framework. Finally, the ideal mHealth-application should above all be trustworthy and easy to use.


Assuntos
Artrite Reumatoide , Aplicativos Móveis , Telemedicina , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/terapia , Grupos Focais , Humanos , Pesquisa Qualitativa
7.
Arthritis Res Ther ; 23(1): 210, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380557

RESUMO

BACKGROUND: First-degree relatives (FDRs) of people with rheumatoid arthritis (RA) have a fourfold increased risk of developing RA. The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire was developed to document symptoms in persons at risk of RA. The aims of this study were (1) to describe symptoms in a cohort of FDRs of patients with RA overall and stratified by seropositivity and elevated CRP and (2) to determine if patient characteristics were associated with symptoms suggestive of RA. METHODS: A cross-sectional study of FDRs of patients with RA, in the PREVeNT-RA study, who completed a study questionnaire, provided a blood sample measured for rheumatoid factor, anti-CCP and CRP and completed the SPARRA questionnaire. Moderate/severe symptoms and symmetrical, small and large joint pain were identified and described. Symptoms associated with both seropositivity and elevated CRP were considered suggestive of RA. Logistic regression was used to determine if symptoms suggestive of RA were associated with patient characteristics. RESULTS: Eight hundred seventy participants provided all data, 43 (5%) were seropositive and 122 (14%) had elevated CRP. The most frequently reported symptoms were sleep disturbances (20.3%) and joint pain (17.9%). Symmetrical and small joint pain were 11.3% and 12.8% higher, respectively, in those who were seropositive and 11.5% and 10.7% higher in those with elevated CRP. In the logistic regression model, seropositivity, older age and feeling depressed were associated with increased odds of small and symmetrical joint pain. CONCLUSIONS: This is the first time the SPARRA questionnaire has been applied in FDRs of patients with RA and has demonstrated that the presence of symmetrical and small joint pain in this group may be useful in identifying people at higher risk of developing RA.


Assuntos
Artrite Reumatoide , Autoanticorpos , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Estudos Transversais , Humanos , Peptídeos Cíclicos , Fator Reumatoide , Inquéritos e Questionários
8.
Int J Rheum Dis ; 24(9): 1106-1111, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34375036

RESUMO

Rheumatoid arthritis (RA) is a major health burden in Asia Pacific affecting the quality of life of patients and consuming healthcare resources. According to recent estimates from the World Health Organization-International League Against Rheumatism-Community Oriented Program for Control of Rheumatic Diseases, prevalence is around 0.3%-0.5%. Management guidelines have helped to improve treatment across this diverse region. To gain better insight into current real-world management applications in view of these guidelines, virtual meetings were conducted in mid-2020 to explore perspectives of rheumatologists and patients, as well as discuss the impact of coronavirus disease 2019 on RA management. Patients and rheumatologists from Hong Kong, Malaysia, Singapore, the Philippines, Thailand, India, Pakistan, and Taiwan were included, representing a diverse mix of healthcare systems, wealth, ethnicity and culture. Despite many countries having prospered in recent years, similar challenges in RA diagnosis and treatment were identified. The daily impact and patient experience of RA were also similar across countries, marked by "silent" pain and disability, and universal misunderstanding of the disease. Late diagnosis and treatment, and barriers to access to appropriate treatment, remain problematic. The experience shared by Taiwan offers a glimmer of hope, however, wherein patient advocacy groups have succeeded in being included in policy-making decisions and securing access to advanced treatment. Real-world solutions that pay heed to the unique local needs and diversity of Asia Pacific are required to improve RA management, which will take time. In the interim, help can be sought from the trained, non-rheumatologist community to reduce some of the disease burden.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , COVID-19 , Manejo da Dor/tendências , Padrões de Prática Médica/tendências , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Ásia/epidemiologia , Humanos , Resultado do Tratamento
9.
Talanta ; 234: 122705, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364500

RESUMO

This paper reports the preparation of the first dual electrochemical immunosensor for the simultaneous determination of the CXCL7 chemokine and the MMP3 metalloproteinase as relevant biomarkers for the better diagnosis and monitoring of rheumatoid arthritis derived from the multiple biomarkers measurement. The developed immunosensor involves the use of carboxylated magnetic beads (MBs) and dual screen-printed carbon electrodes (SPdCEs). Sandwich-type configurations implied the covalent immobilization of specific anti-CXCL7 (cAb1) or anti-MMP3 (cAb2) capture antibodies onto MBs and the use of biotinylated detection antibodies with further labelling with HRP-Strept conjugates. The resulting MBS bioconjugates were magnetically captured on the respective working electrode of the SPdCE and the determination of the antigens was accomplished by measuring the amperometric responses of H2O2 mediated by hydroquinone (HQ) at a potential value of -0.20 V. The dual immunosensor provided calibration plots with linear ranges between 1 and 75 ng mL-1 (CXCL7) (R2 = 0.997) and from 2.0 to 2000 pg mL-1 (MMP3) (R2 = 0.998) with detection limits of 0.8 ng mL-1 and 1.2 pg mL-1, respectively. The assay took 2 h 20 min for the simultaneous determination of both biomarkers. The dual immunosensor was successfully applied to the analysis of human serum from positive and negative RA patients.


Assuntos
Artrite Reumatoide , Técnicas Biossensoriais , Artrite Reumatoide/diagnóstico , Biomarcadores , Quimiocinas , Técnicas Eletroquímicas , Eletrodos , Humanos , Peróxido de Hidrogênio , Imunoensaio , Limite de Detecção , Metaloproteinase 3 da Matriz , beta-Tromboglobulina
10.
Medicine (Baltimore) ; 100(28): e26445, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260526

RESUMO

RATIONALE: Several diseases feature tumors, or tumor-mimicking lesions, that further invade the bone and surrounding joints of the wrist region. Here, we describe 3 rare cases of multiple destructed carpal bones and adjacent joints in different disease entities confirmed via pathologic diagnosis. PATIENT CONCERNS: All 3 cases were examined between January 2016 and December 2019. Three patients presented with similar clinical manifestations and radiographic features, with multiple osteolytic lesions in the carpal bones and metacarpal bone base. DIAGNOSES: The 3 cases were diagnosed as diffuse type tenosynovial giant cell tumor, calcifying aponeurotic fibroma, and rheumatoid arthritis. INTERVENTIONS: Separate, experienced radiologist and pathologist took part in the interpretation and compartmentalization of radiographs and pathological findings, respectively. Even magnetic resonance imaging could not achieve a diagnosis; surgical excision was therefore required, with subsequent pathological assessment for treatment and final diagnosis. OUTCOMES: functional outcomes also differed among patients, poorest in rheumatoid arthritis patient. LESSONS: We report 3 rare disease entities, presenting with multifocal osteolytic lesions in the wrist. They all presented with similar clinical manifestations, and the final diagnoses were made via pathological evaluation. Compared with tenosynovial giant cell tumor and calcifying aponeurotic fibroma, rheumatoid arthritis had the poorest outcome.


Assuntos
Artrite Reumatoide/patologia , Ossos do Carpo/patologia , Fibroma Ossificante/patologia , Tumor de Células Gigantes de Bainha Tendinosa/patologia , Neoplasias de Tecidos Moles/patologia , Artrite Reumatoide/diagnóstico , Ossos do Carpo/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Fibroma Ossificante/diagnóstico , Tumor de Células Gigantes de Bainha Tendinosa/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Osteólise/diagnóstico por imagem , Osteólise/patologia , Neoplasias de Tecidos Moles/diagnóstico
11.
Trials ; 22(1): 450, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261530

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease that severely impacts quality of life. Currently available medications for the treatment of RA have adverse side effects. Emerging evidence suggests that intradermal acupuncture (IA) is feasible and safe for patients, but its application in RA patients has not been examined. Our study aims to explore the efficacy and safety of IA for the treatment of RA. METHODS: This study is a randomised, sham-controlled, patient-outcome assessor-statistician blind trial that aims to evaluate the effects of IA in patients with RA. We will recruit 132 patients aged ≥ 18 years with a diagnosis of RA. Patients will be randomly allocated with a 1:1 ratio to IA or sham IA groups. Both groups will receive basic treatment and nursing routines for RA. The experimental group will receive actual IA treatment, whereas the control group will receive sham IA treatment. All patients will receive one course of treatment (i.e., four consecutive treatment sessions with an intervening 1-day interval). Primary outcomes will be traditional Chinese medicine (TCM) syndromes before and after a treatment course and Health Assessment Questionnaire (HAQ) scores. Secondary outcomes will be disease activity score 28 (DAS28) and levels of serum C-reactive protein (CRP). Outcome measures will be collected pre- and post-treatment. DISCUSSION: This study aims to provide high-quality evidence for the efficacy and safety of IA for treating RA. In addition, the results will provide references for selection of acupoints for other syndromes in clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000038028 . Registered on 8 September 2020.


Assuntos
Terapia por Acupuntura , Artrite Reumatoide , Terapia por Acupuntura/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/terapia , Humanos , Medicina Tradicional Chinesa , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
12.
Arthritis Res Ther ; 23(1): 178, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229736

RESUMO

BACKGROUND: We developed a model to predict remissions in patients treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs) and to identify important clinical features associated with remission using explainable artificial intelligence (XAI). METHODS: We gathered the follow-up data of 1204 patients treated with bDMARDs (etanercept, adalimumab, golimumab, infliximab, abatacept, and tocilizumab) from the Korean College of Rheumatology Biologics and Targeted Therapy Registry. Remission was predicted at 1-year follow-up using baseline clinical data obtained at the time of enrollment. Machine learning methods (e.g., lasso, ridge, support vector machine, random forest, and XGBoost) were used for the predictions. The Shapley additive explanation (SHAP) value was used for interpretability of the predictions. RESULTS: The ranges for accuracy and area under the receiver operating characteristic of the newly developed machine learning model for predicting remission were 52.8-72.9% and 0.511-0.694, respectively. The Shapley plot in XAI showed that the impacts of the variables on predicting remission differed for each bDMARD. The most important features were age for adalimumab, rheumatoid factor for etanercept, erythrocyte sedimentation rate for infliximab and golimumab, disease duration for abatacept, and C-reactive protein for tocilizumab, with mean SHAP values of - 0.250, - 0.234, - 0.514, - 0.227, - 0.804, and 0.135, respectively. CONCLUSIONS: Our proposed machine learning model successfully identified clinical features that were predictive of remission in each of the bDMARDs. This approach may be useful for improving treatment outcomes by identifying clinical information related to remissions in patients with rheumatoid arthritis.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Adalimumab/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Inteligência Artificial , Produtos Biológicos/uso terapêutico , Etanercepte/uso terapêutico , Humanos , Aprendizado de Máquina
13.
Int J Clin Pharmacol Ther ; 59(9): 618-626, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34281633

RESUMO

OBJECTIVE: The relative efficacy and tolerability of tocilizumab, sarilumab, and sirukumab as monotherapy were assessed and compared with those of adalimumab in patients with rheumatoid arthritis (RA) who were intolerant to or responded inadequately to methotrexate (MTX). MATERIALS AND METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tocilizumab, sarilumab, and sirukumab, and adalimumab in RA patients who are intolerant to or show an inadequate response to MTX. RESULTS: Three RCTs comprising 1,066 patients met the inclusion criteria. Tocilizumab 8 mg monotherapy was associated with the most favorable surface under the cumulative ranking curve (SUCRA) for the ACR20 response rate. Compared with adalimumab, tocilizumab, and sarilumab as monotherapy showed significantly higher ACR20 response rates. Ranking probability based on SUCRA indicated that tocilizumab 8 mg had the highest probability of being the best choice for achieving ACR20 response rate, followed by sarilumab 200 mg, adalimumab 40 mg, and sirukumab 50 mg. Moreover, the ACR50 response rate showed a similar distribution pattern to that of ACR20. Regarding adverse events, the ranking probability based on SUCRA indicated that sarilumab 200 mg was possibly the safest, followed by adalimumab 40 mg, tocilizumab 8 mg, and sirukumab 50 mg. However, the number of patients who experienced serious adverse events did not differ significantly between these biologics. CONCLUSION: Based on ACR20 and ACR50 response rates, monotherapy with tocilizumab 8 mg, followed by sarilumab and sirukumab monotherapy, was optimal for patients with RA responding inadequately to MTX or showing intolerance.


Assuntos
Antirreumáticos , Artrite Reumatoide , Adalimumab/efeitos adversos , Anticorpos Monoclonais Humanizados , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Quimioterapia Combinada , Humanos , Metotrexato/efeitos adversos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Clin Exp Rheumatol ; 39(4): 705-720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34238403

RESUMO

Management of rheumatoid arthritis (RA) has evolved over the years as a result of better understanding of the role of different therapeutic strategies, as well as following an increasing availability of new disease-modifying antirheumatic drugs. However, the role of patients in sharing decisions, as well as the rules informing precision medicine or the principles to follow in case of specific comorbidities or extra-articular manifestations are still areas for improvement. Moreover, in 2020, the novel Coronavirus disease-19 outbreak has completely changed many attitudes in terms of assessment and treatment paradigms in most clinical diseases, including RA. In this narrative review, the authors report their specific point of view on the management of RA, based on a critical revision of literature published in 2020, focusing on relevant novelties and future research directions.


Assuntos
Antirreumáticos , Artrite Reumatoide , COVID-19 , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Comorbidade , Humanos , SARS-CoV-2
15.
Anal Chim Acta ; 1174: 338699, 2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34247731

RESUMO

Anisotropic organic-inorganic hybrid nanoparticles possessing different functionalities and physicochemical properties from each compartment have attracted significant interest for the development of advanced functional materials. Moreover, their self-assembled structures exhibit unique optical properties for photonics-based biosensing. We report herein the fabrication of anisotropic bimetal-polymer nanoparticles (ABPNs) via combination of oxidative polymerization and additional growth of metallic nanoparticles on Au seeds as well as their directional clustering mediated via noncovalent interactions. Polymerization of anilines for poly (aniline) shell was conducted by reducing silver nitrate onto the Au seed in the presence of a surfactant, giving rise to spatially distinct bimetallic Au core and Ag shell compartment and the poly (aniline) counter-one that comprise the ABPNs. Furthermore, ABPNs were directionally clustered in a controlled manner via hydrophobic interaction, when the bimetallic compartment was selectively modified. These nanoclusters showed highly enhanced optical properties owing to the increased electromagnetic fields while the poly (aniline) being used to offer antibody binding capacity. Taking advantages of those properties of the ABPN nanoclusters, surface-enhanced Raman scattering (SERS) intensity-based quantification of two different biomarkers: autoantibodies against cyclic citrullinated peptide and rheumatoid factor was demonstrated using ABPN nanoclusters as SERS nanoprobes. Conclusively, this work has great potential to satisfy a need for multiplexing in diagnosis of early stage of rheumatoid arthritis.


Assuntos
Artrite Reumatoide , Nanoestruturas , Compostos de Anilina , Artrite Reumatoide/diagnóstico , Ouro , Humanos , Análise Espectral Raman
16.
BMJ Open ; 11(7): e048409, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261688

RESUMO

PURPOSE: Rheumatoid arthritis (RA) is an insidious autoimmune disease, with an immunological onset years before diagnosis. Early interventions in preclinical stages could prevent or minimise the progression towards irreversible joint damage. The SCREEN-RA cohort (Evaluation of a SCREENing strategy for Rheumatoid Arthritis) aims to characterise the preclinical stages of the disease, to identify environmental risk factors, and to discover or validate novel biomarkers predictive for RA development. PARTICIPANTS: SCREEN-RA includes an at-risk population for RA, namely first-degree relatives of patients with established RA. FINDINGS TO DATE: The cohort started in 2009 is composed of mostly asymptomatic healthy individuals (total n=1458, 7262 person-years), with a mean age of 44 years at enrolment, 74% female and 91% Caucasian ethnicity. During the study period, 16 participants have developed RA. All participants provide baseline serum, DNA and RNA samples, and in a subset, stool samples and oral examination are performed for microbiota assessment. At enrolment, 10% of participants had asymptomatic autoimmunity associated with RA (n=147), 10% presented 'clinically suspect arthralgias' (n=143) and 3% reported arthralgias in conjunction with autoimmunity or high genetic risk (n=51). Studies with this cohort have uncovered risk factors for RA development, such as female hormonal factors, poor oral health or intestinal dysbiosis. FUTURE PLANS: Future directions include immunological and 'multiomics' approaches to discover new biological markers of progression towards RA, as well as testing preventive interventions in 'high-risk' population.


Assuntos
Artrite Reumatoide , Grupos Étnicos , Adulto , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/genética , Autoanticorpos , Estudos de Coortes , Feminino , Humanos , Masculino , Suíça/epidemiologia
17.
Trials ; 22(1): 433, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229728

RESUMO

BACKGROUND: Adaptive model-based dose-finding designs have demonstrated advantages over traditional rule-based designs but have increased statistical complexity but uptake has been slow especially outside of cancer trials. TRAFIC is a multi-centre, early phase trial in rheumatoid arthritis incorporating a model-based design. METHODS: A Bayesian adaptive dose-finding phase I trial rolling into a single-arm, single-stage phase II trial. Model parameters for phase I were chosen via Monte Carlo simulation evaluating objective performance measures under clinically relevant scenarios and incorporated stopping rules for early termination. Potential designs were further calibrated utilising dose transition pathways. DISCUSSION: TRAFIC is an MRC-funded trial of a re-purposed treatment demonstrating that it is possible to design, fund and implement a model-based phase I trial in a non-cancer population within conventional research funding tracks and regulatory constraints. The phase I design allows borrowing of information from previous trials, all accumulated data to be utilised in decision-making, verification of operating characteristics through simulation, improved understanding for management and oversight teams through dose transition pathways. The rolling phase II design brings efficiencies in trial conduct including site and monitoring activities and cost. TRAFIC is the first funded model-based dose-finding trial in inflammatory disease demonstrating that small phase I/II trials can have an underlying statistical basis for decision-making and interpretation. TRIAL REGISTRATION: Trials Registration: ISRCTN, ISRCTN36667085 . Registered on September 26, 2014.


Assuntos
Artrite Reumatoide , Neoplasias , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Teorema de Bayes , Simulação por Computador , Relação Dose-Resposta a Droga , Humanos , Projetos de Pesquisa
18.
Arthritis Res Ther ; 23(1): 184, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238346

RESUMO

BACKGROUND: The new concept of difficult-to-treat rheumatoid arthritis (D2T RA) refers to RA patients who remain symptomatic after several lines of treatment, resulting in a high patient and economic burden. During a hackathon, we aimed to identify and predict D2T RA patients in structured and unstructured routine care data. METHODS: Routine care data of 1873 RA patients were extracted from the Utrecht Patient Oriented Database. Data from a previous cross-sectional study, in which 152 RA patients were clinically classified as either D2T or non-D2T, served as a validation set. Machine learning techniques, text mining, and feature importance analyses were performed to identify and predict D2T RA patients based on structured and unstructured routine care data. RESULTS: We identified 123 potentially new D2T RA patients by applying the D2T RA definition in structured and unstructured routine care data. Additionally, we developed a D2T RA identification model derived from a feature importance analysis of all available structured data (AUC-ROC 0.88 (95% CI 0.82-0.94)), and we demonstrated the potential of longitudinal hematological data to differentiate D2T from non-D2T RA patients using supervised dimension reduction. Lastly, using data up to the time of starting the first biological treatment, we predicted future development of D2TRA (AUC-ROC 0.73 (95% CI 0.71-0.75)). CONCLUSIONS: During this hackathon, we have demonstrated the potential of different techniques for the identification and prediction of D2T RA patients in structured as well as unstructured routine care data. The results are promising and should be optimized and validated in future research.


Assuntos
Artrite Reumatoide , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Bases de Dados Factuais , Humanos , Aprendizado de Máquina
19.
Arthritis Res Ther ; 23(1): 189, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256800

RESUMO

BACKGROUND: The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. METHODS: Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. RESULTS: IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. CONCLUSION: IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815 .


Assuntos
Antirreumáticos , Artrite Reumatoide , Anticorpos Anti-Proteína Citrulinada , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Autoanticorpos , Humanos , Interferon-alfa/uso terapêutico , Fator Reumatoide
20.
Arthritis Res Ther ; 23(1): 201, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34311770

RESUMO

BACKGROUND: The increased risk of cardiovascular events (CVE) in rheumatoid arthritis (RA) is not fully explained by traditional risk factors. Immuno-inflammatory mechanisms and autoantibodies could be involved in the pathogenesis of atherosclerotic disease. It has been suggested that anti-phosphorylcholine antibodies (anti-PC) of the IgM subclass may have atheroprotective effects. Here, we aimed to investigate the association between levels of IgM anti-PC antibodies with CVE in patients with early RA. METHODS: The study population was derived from the BARFOT early RA cohort, recruited in 1994-1999. The outcome of incident CVE (AMI, angina pectoris, coronary intervention, ischemic stroke, TIA) was tracked through the Swedish Hospital Discharge and the National Cause of Death Registries. Sera collected at inclusion and the 2-year visit were analyzed with ELISA to determine levels of anti-PC IgM. The Kaplan-Meier estimates and Cox proportional hazards regression models were used to compare CV outcome in the groups categorized by baseline median level of IgM anti-PC. RESULTS: In all, 653 patients with early RA, 68% women, mean (SD) age 54.8 (14.7) years, DAS28 5.2 (1.3), 68% seropositive, and without prevalent CVD, were included. During the follow-up of mean 11.7 years, 141 incident CVE were recorded. Baseline IgM anti-PC above median was associated with a reduction in risk of incident CVE in patients aged below 55 years at inclusion, HR 0.360 (95% CI, 0.142-0.916); in males, HR 0.558 (0.325-0.958); in patients with BMI above 30 kg/m2, HR 0.235 (0.065-0.842); and in those who did not achieve DAS28 remission at 1 year, HR 0.592 (0.379-0.924). The pattern of associations was confirmed in the models with AUC IgM anti-PC over 2 years. CONCLUSION: Protective effects of higher levels of innate IgM anti-PC autoantibodies on CVE were detected in younger patients with RA and those at high risk of CVE: males, presence of obesity, and non-remission at 1 year.


Assuntos
Artrite Reumatoide , Aterosclerose , Doenças Cardiovasculares , Idoso , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Autoanticorpos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Feminino , Humanos , Imunoglobulina M , Masculino , Pessoa de Meia-Idade , Fosforilcolina , Fatores de Risco
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