RESUMO
There is a growing appreciation that both giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely interrelated conditions that have significant overlap in aetiology, clinical characteristics and treatment regimens. Subclinical GCA in PMR is becoming increasingly recognised, and there is evolving evidence that this may be a more aggressive disease phenotype than PMR. Ultrasound (US) lends itself well as a screening tool for GCA in PMR; it is inexpensive, non-invasive, widely available, lacks ionising radiation, may be performed at the bedside and is recommended by EULAR as a first-line investigation for suspected GCA. There is insufficient evidence to currently recommend that all patients with PMR should have a US assessment for vascular involvement. However, as clinical and laboratory parameters alone do not accurately diagnose patients with subclinical GCA, we suggest that vascular US will be increasingly performed by rheumatologists in practice to identify these patients with PMR, preferably as part of larger prospective outcome studies.
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Arterite de Células Gigantes , Polimialgia Reumática , Ultrassonografia , Humanos , Arterite de Células Gigantes/diagnóstico por imagem , Polimialgia Reumática/diagnóstico por imagem , Artérias Temporais/diagnóstico por imagem , Artérias Temporais/patologia , Ultrassonografia/métodosRESUMO
OBJECTIVES: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. METHODS: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. RESULTS: In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. CONCLUSION: This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.
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Clínicos Gerais , Arterite de Células Gigantes , Polimialgia Reumática , Humanos , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamento farmacológico , Reumatologistas , Glucocorticoides/uso terapêutico , Prednisolona/uso terapêutico , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: To establish a framework by which experts define disease subsets in systemic sclerosis associated interstitial lung disease (SSc-ILD). METHODS: A conceptual framework for subclinical, clinical and progressive ILD was provided to 83 experts, asking them to use the framework and classify actual SSc-ILD patients. Each patient profile was designed to be classified by at least four experts in terms of severity and risk of progression at baseline; progression was based on 1-year follow-up data. A consensus was reached if ≥75% of experts agreed. Experts provided information on which items were important in determining classification. RESULTS: Forty-four experts (53%) completed the survey. Consensus was achieved on the dimensions of severity (75%, 60 of 80 profiles), risk of progression (71%, 57 of 80 profiles) and progressive ILD (60%, 24 of 40 profiles). For profiles achieving consensus, most were classified as clinical ILD (92%), low risk (54%) and stable (71%). Severity and disease progression overlapped in terms of framework items that were most influential in classifying patients (forced vital capacity, extent of lung involvement on high resolution chest CT [HRCT]); risk of progression was influenced primarily by disease duration. CONCLUSIONS: Using our proposed conceptual framework, international experts were able to achieve a consensus on classifying SSc-ILD patients along the dimensions of disease severity, risk of progression and progression over time. Experts rely on similar items when classifying disease severity and progression: a combination of spirometry and gas exchange and quantitative HRCT.
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Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Doenças Pulmonares Intersticiais/complicações , Escleroderma Sistêmico/complicações , Capacidade Vital , Tomografia Computadorizada por Raios X/métodos , Índice de Gravidade de Doença , PulmãoRESUMO
The coronavirus disease 2019 (COVID-19) pandemic revealed that our understanding of infectious complications and strategies to mitigate severe infections in patients with glomerular diseases is limited. Beyond COVID-19, there are several infections that specifically impact care of patients receiving immunosuppressive measures. This review will provide an overview of six different infectious complications frequently encountered in patients with glomerular diseases, and will focus on recent achievements in terms of vaccine developments and understanding of the use of specific antimicrobial prophylaxis. These include influenza virus, Streptococcus pneumoniae, reactivation of a chronic or past infection with hepatitis B virus in cases receiving B-cell depletion, reactivation of cytomegalovirus, and cases of Pneumocystis jirovecii pneumonia in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Varicella zoster virus infections are particularly frequent in patients with systemic lupus erythematosus and an inactivated vaccine is available to use as an alternative to the attenuated vaccine in patients receiving immunosuppressants. As with COVID-19 vaccines, vaccine responses are generally impaired in older patients, and after recent administration of B-cell depleting agents, and high doses of mycophenolate mofetil and other immunosuppressants. Strategies to curb infectious complications are manifold and will be outlined in this review.
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Hospedeiro Imunocomprometido , Nefropatias , Idoso , Humanos , Anti-Infecciosos , COVID-19/complicações , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Imunossupressores/uso terapêutico , Nefropatias/complicações , VacinasRESUMO
OBJECTIVES: To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD). METHODS: Physician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively. RESULTS: The study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD). CONCLUSION: The safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.
Assuntos
Antirreumáticos , COVID-19 , Doenças Musculoesqueléticas , Doenças Reumáticas , Idoso , Antirreumáticos/efeitos adversos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Doenças Musculares , Doenças Musculoesqueléticas/induzido quimicamente , Doenças Musculoesqueléticas/tratamento farmacológico , Doenças Musculoesqueléticas/epidemiologia , Sistema de Registros , Doenças Reumáticas/tratamento farmacológico , Reumatologistas , SARS-CoV-2 , Vacinação/efeitos adversosRESUMO
The first EULAR provisional recommendations on the management of rheumatic and musculoskeletal diseases (RMDs) in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), largely based on expert opinion, were published in June 2020. Since then, an unprecedented number of clinical studies have accrued in the literature. Several SARS-CoV-2 vaccines have been approved for population-wide vaccination programmes in EULAR-affiliated countries. Studies regarding vaccination of patients with (inflammatory) RMDs have released their first results or are underway.EULAR found it opportune to carefully review to what extent the initially consensus expert recommendations stood the test of time, by challenging them with the recently accumulated body of scientific evidence, and by incorporating evidence-based advice on SARS-CoV-2 vaccination. EULAR started a formal (first) update in January 2021, performed a systematic literature review according to EULAR's standard operating procedures and completed a set of updated overarching principles and recommendations in July 2021. Two points to consider were added in November 2021, because of recent developments pertaining to additional vaccination doses.
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COVID-19 , Doenças Musculoesqueléticas , Doenças Reumáticas , Humanos , SARS-CoV-2 , Doenças Reumáticas/tratamento farmacológico , Vacinas contra COVID-19 , COVID-19/prevenção & controle , VacinaçãoRESUMO
OBJECTIVES: Although evidence is accumulating globally, data on outcomes in rheumatic disease and COVID-19 in Ireland are limited. We used data from the COVID-19 Global Rheumatology Alliance (C19-GRA) to describe time-varying COVID-19 outcomes for people with rheumatic disease in Ireland. METHODS: Data entered into the C19-GRA provider registry from Ireland between 24 March 2020 and 9 July 2021 were analysed. Differences in the likelihood of hospitalization and mortality according to demographic and clinical variables were investigated using Chi-squared test or Fisher's exact test, as appropriate. Trends in odds of hospitalization and mortality over time were investigated using logistic regression with the time period as a categorical variable. RESULTS: Of 212 cases included, 59.4% were female and median age was 58.0 years (range 13-96). Of the 212 cases, 92 (43%) were hospitalized and 22 (10.4%) died. Increasing age, a diagnosis of gout, ever smoking, glucocorticoid use, having comorbidities and specific comorbidities of cancer, cardiovascular and pulmonary disease were more common in those hospitalized. A diagnosis of inflammatory arthritis, csDMARD and/or b/tsDMARD use were less frequent in those hospitalized. Increasing age, a diagnosis of gout, ever smoking, having comorbidities and specific comorbidities of obesity, cardiovascular and pulmonary disease were more common in those who died. Odds of hospitalization or mortality did not change over time. CONCLUSION: No temporal trend was observed in either COVID-19-related hospitalization or mortality outcomes for people with rheumatic disease in Ireland.
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COVID-19 , Gota , Doenças Reumáticas , Reumatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Feminino , Humanos , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Doenças Reumáticas/epidemiologia , SARS-CoV-2 , Adulto JovemRESUMO
Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) are a feature of the idiopathic inflammatory myopathies (IIM), but are also seen in other rheumatic diseases, and in individuals with no clinical symptoms. The aim of this study was to assess the clinical utility of MSA and MAA and in particular the clinical relevance of weakly positive results. We included all patients at our institution who had at least one positive result on the Immunoblot EUROLINE myositis panel over a 6-year period (2015-2020). Associations with clinical features and final diagnosis were evaluated. Eighty-seven of 225 (39%) myositis panel tests met the inclusion criteria. There were 52 strong positives and 35 weak positives for one or more MSA/MAAs. Among the strong positive group, 15% (8/52) were diagnosed with IIM, 34.6% (18/52) with interstitial lung disease, 7.7% (4/52) with anti-synthetase syndrome, 25% (13/52) with connective tissue disease, and others accounted for 25% (13/52). In weak-positive cases, only 14% (5/35) had connective tissue disease and none had IIM. 60% (21/35) of weak-positive cases were not associated with a specific rheumatic disease. A significant number of positive myositis panel results, particularly weak positives, are not associated with IIM or CTD.
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Anticorpos/sangue , Miosite/imunologia , Adulto , Idoso , Anticorpos/imunologia , Autoanticorpos/sangue , Biomarcadores/sangue , Feminino , Humanos , Imunoensaio/métodos , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite/diagnóstico , Estudos RetrospectivosRESUMO
MTX, which is the anchor-drug for the treatment of RA, has been associated with lung injury and in particular with MTX-related pneumonitis (M-pneu). Although the frequency of M-pneu has been reported to range between 0.3 and 11.6%, more recent studies and meta-analyses have challenged that, suggesting that it is less common than previously thought. M-pneu is considered a hypersensitivity reaction usually occuring early after MTX commencement, and to be dose-independent. Furthermore, it does not seem to be truly related to the development of interstitial lung disease observed in some patients as part of the natural history of RA (RA-ILD). On the other hand, there are data suggesting that clinicians should be cautious when commencing MTX in patients with pre-existing lung disease. However, treatment should not be delayed or limited in progressive RA that could lead to RA-ILD, and MTX remains one of the central players in the treat-to-target approach. In this review, we aimed to summarize the current evidence from observational studies and clinical trials on lung disease in MTX-treated RA patients. We focus the discussion on the lack of association between M-pneu and RA-ILD.
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Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Doenças Pulmonares Intersticiais/induzido quimicamente , Metotrexato/efeitos adversos , Ensaios Clínicos como Assunto , Humanos , Estudos Observacionais como Assunto , Pneumonia/induzido quimicamenteRESUMO
OBJECTIVES: The diagnosis of giant cell arteritis (GCA) is primarily a clinical one. Temporal artery (TA) ultrasound (US) has been proposed as a new diagnostic tool. We aimed to assess the performance characteristics of TA US in routine clinical practice. METHODS: All patients presenting with suspected GCA to our institution are recruited to a prospective registry. Patients who had both a TA US and biopsy (TAB) performed at the time of presentation were included in the current study. The performance characteristics of TA US was compared to physician diagnosis at six months following presentation. Predictive factors for a positive TA US were explored in univariate and multivariable logistic regression analyses. RESULTS: 162 patients were included, 123 (76%) with GCA. Mean (SD) duration of glucocorticoid therapy was 6.6 days (19.4) at the time of TA US. TA US had a sensitivity of 52.8% (95%CI 43.7, 61.9) and specificity of 71.8% (95%CI 54.9, 84.5) for the diagnosis of GCA. Glucocorticoid duration did not significantly impact the results. A sequential strategy of TA US followed by TAB in the case of a negative US had a sensitivity of 78.9% (95%CI 70.1, 85.5) and specificity of 71.8% (95%CI 54.9, 84.5), equivalent to a simultaneous testing strategy. The only factor independently predictive of a positive TA US was male sex (OR 5.53, 95% CI 2.72 to 11.22, p<0.001). CONCLUSIONS: TA US is potentially useful in the diagnosis of GCA; however, interpretation of its results requires knowledge of the performance characteristics in the target population.
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Arterite de Células Gigantes , Artérias Temporais , Ultrassonografia/métodos , Biópsia , Estudos de Coortes , Feminino , Arterite de Células Gigantes/diagnóstico , Humanos , Masculino , Estudos Prospectivos , Artérias Temporais/diagnóstico por imagemRESUMO
Background and Purpose- The diagnosis of giant-cell arteritis (GCA) is challenging. Superficial temporal artery biopsy and ultrasound are positive in only 50%. We evaluated computed tomographic angiography (CTA) of the head in GCA. Methods- This case-control study was performed using a prospective GCA registry. Cases presented with stroke symptoms, had a CTA, and were subsequently diagnosed with GCA. Age- and sex-matched controls presented with stroke symptoms, had a CTA, and were not diagnosed with GCA. CTAs were evaluated for the presence of superficial temporal artery abnormalities. Results- Fourteen cases met the inclusion criteria and were matched with 14 controls. Blurred vessel wall margins and perivascular enhancement was found in 10 cases (71.4%) and 2 controls (14.3%). CTA has an accuracy of 78.6%, sensitivity of 71.4%, and a specificity of 85.7% for GCA. Conclusions- CTA detects superficial temporal artery abnormalities in GCA. This may facilitate early diagnosis and prompt implementation of potentially sight-saving and stroke-preventing treatment.
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Arterite de Células Gigantes/diagnóstico por imagem , Artérias Temporais/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: The pathogenesis of giant cell arteritis (GCA) remains unclear. TH1 and TH17 pathways are implicated, but the proximal initiators and effector cytokines are unknown. Our aim was to assess the role of interleukin 12 (IL-12) and interleukin 23 (IL-23) in GCA pathogenesis. METHODS: IL-12 and IL-23 expression were quantified by immunohistochemistry in temporal artery biopsies (TABs). Temporal artery (TA) explant, peripheral blood mononuclear cell (PBMC) and myofibroblast outgrowth culture models were established. PBMCs and TA explants were cultured for 24 hours in the presence or absence of IL-12 (50 ng/mL) or IL-23 (10 ng/mL). Gene expression in TA was quantified by real-time PCR and cytokine secretion by ELISA. Myofibroblast outgrowths were quantified following 28-day culture. RESULTS: Immunohistochemistry demonstrated increased expression of interleukin 12p35 (IL-12p35) and interleukin 23p19 (IL-23p19) in biopsy-positive TAs, localised to inflammatory cells. IL-12p35 TA expression was significantly increased in those with cranial ischaemic complications (p=0.026) and large vessel vasculitis (p=0.006). IL-23p19 TA expression was increased in those with two or more relapses (p=0.007). In PBMC cultures, exogenous IL-12 significantly increased interleukin 6 (IL-6) (p=0.009), interleukin 22 (IL-22) (p=0.003) and interferon γ (IFN-γ) (p=0.0001) and decreased interleukin 8 (IL-8) (p=0.0006) secretion, while exogenous IL-23 significantly increased IL-6 (p=0.029), IL-22 (p=0.001), interleukin 17A (IL-17A) (p=0.0003) and interleukin 17F (IL-17F) (p=0.012) secretion. In ex vivo TA explants, IL-23 significantly increased gene expression of IL-8 (p=0.0001) and CCL-20 (p=0.027) and protein expression of IL-6 (p=0.002) and IL-8 (p=0.004). IL-12 (p=0.0005) and IL-23 (p<0.0001) stimulation increased the quantity of myofibroblast outgrowths from TABs. CONCLUSION: IL-12 and IL-23 play central and distinct roles in stimulating inflammatory and proliferative pathways relevant to GCA pathogenesis.
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Arterite de Células Gigantes/imunologia , Arterite de Células Gigantes/patologia , Interleucina-12/imunologia , Interleucina-23/imunologia , Proliferação de Células/fisiologia , Humanos , Inflamação/imunologia , Inflamação/patologia , Artérias Temporais/patologiaRESUMO
PURPOSE OF REVIEW: Osteoarthritis (OA) is the most common form of joint disease globally and is associated with significant morbidity and disability. Increasing evidence points to an important inflammatory component in the development and progression of OA. The precise pathways involved in OA inflammatory processes remain to be clarified. Basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP) crystals can induce inflammation and arthritis and recent studies point to a potential pathogenic role in OA. In the light of this evidence, we explore the relationship and potential mechanistic pathways linking calcium-containing crystals and OA. RECENT FINDINGS: CPP crystals induce inflammation through the NLRP3 inflammasome while BCP crystals mediate both NLRP3 dependent and independent effects. BCP crystals have been demonstrated to induce key mitogenic and inflammatory pathways and contribute to cartilage degradation. Calcium-containing crystals induce key inflammatory pathways and may represent an attractive novel target in OA, a condition devoid of effective treatments.
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Fosfatos de Cálcio/análise , Osteoartrite/metabolismo , Pirofosfato de Cálcio/análise , Cristalização , Humanos , Articulações/química , Líquido Sinovial/químicaRESUMO
Patients with gout have an increased risk of cardiovascular events. The glycoprotein VI (GPVI) receptor is found exclusively on platelets and megakaryocytes, is proteolytically cleaved upon platelet activation, and detectable in plasma as soluble GPVI (sGPVI). Therefore, elevated sGPVI is a marker of platelet activation and a risk marker for cardiovascular events. The aim of this study was to assess platelet activation, as measured by plasma sGPVI level in gout. Blood samples were taken from patients with gout or osteoarthritis, and from healthy volunteers. Demographic and clinical data were collected for all participants. Blood samples were processed as double-spun platelet-poor plasma. Plasma sGPVI levels were measured using enzyme-linked immunosorbent assay. Mann-Whitney U test was used to compare groups. In total, 91 patients were included, 27 during gout flare, 41 with intercritical gout, 23 with osteoarthritis, and 53 healthy controls. Median (interquartile range) sGPVI levels were 6.51 ng/mL (4.52, 8.41) in gout flare, 3.58 ng/mL (2.11, 5.55) in intercritical gout, 2.73 ng/mL (2.17, 3.72) in osteoarthritis, and 2.19 ng/mL (1.72, 3.31) in healthy controls. Plasma sGPVI levels in both gout groups were significantly increased compared to healthy controls (p < 0.005 for each), in gout flare compared to osteoarthritis (p < 0.005), and in gout flare compared to intercritical gout (p = 0.001). There was no significant difference in sGPVI levels in gout patients with and without tophi or in those prescribed colchicine. We conclude that patients with gout exhibit platelet hyperactivity as demonstrated by elevated sGPVI levels. Platelet activation is exacerbated in gout, especially during gout flares.
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Plaquetas/metabolismo , Gota/sangue , Ativação Plaquetária , Glicoproteínas da Membrana de Plaquetas/metabolismo , Adulto , Idoso , Plaquetas/patologia , Feminino , Gota/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND: An Illness Severity and Co-morbidity composite score can predict 30-day mortality outcome. METHODS: We computed a summary risk score (RS) for emergency medical admissions and used cluster analysis to define four subsets Results: Four cluster groups were defined. Cluster 1 - RS 7 points (IQR 5, 8) Cluster 2 - 9 (IQR 8, 11), Cluster 3 - 12 (IQR 11, 13) and Cluster 4 - 14 (IQR 13, 15). Clusters predicted 30-day in hospital mortality OR 1.86 (95%CI: 1.82, 1.92); respective rates 1.4% (95% CI: 1.3%, 1.6%), 3.4% (95% CI: 3.1%, 3.6%), 7.8% (95% CI: 7.5%, 8.1%) and 16.5% (95% CI: 15.7%, 17.2%). CONCLUSION: Cluster grouping of Risk Score was age related; strongest outcome determinant was Acute Illness Severity.
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Emergências , Mortalidade Hospitalar , Admissão do Paciente/estatística & dados numéricos , Índice de Gravidade de Doença , Análise por Conglomerados , Comorbidade , Humanos , Prognóstico , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVES: Since the 2007 recommendations for the management of early arthritis have been presented, considerable research has been published in the field of early arthritis, mandating an update of the 2007 European League Against Rheumatism (EULAR) recommendations for management of early arthritis. METHODS: In accordance with the 2014 EULAR Standardised Operating Procedures, the expert committee pursued an approach that was based on evidence in the literature and on expert opinion. The committee involved 20 rheumatologists, 2 patients and 1 healthcare professional representing 12 European countries. The group defined the focus of the expert committee and target population, formulated a definition of 'management' and selected the research questions. A systematic literature research (SLR) was performed by two fellows with the help of a skilled librarian. A set of draft recommendations was proposed on the basis of the research questions and the results of the SLR. For each recommendation, the categories of evidence were identified, the strength of recommendations was derived and the level of agreement was determined through a voting process. RESULTS: The updated recommendations comprise 3 overarching principles and 12 recommendations for managing early arthritis. The selected statements involve the recognition of arthritis, referral, diagnosis, prognostication, treatment (information, education, pharmacological and non-pharmacological interventions), monitoring and strategy. Eighteen items were identified as relevant for future research. CONCLUSIONS: These recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis.
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Antirreumáticos/uso terapêutico , Artrite/diagnóstico , Artrite/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite/terapia , Terapia por Exercício , Glucocorticoides/uso terapêutico , Humanos , Estilo de Vida , Terapia OcupacionalRESUMO
Systemic lupus erythematosus (SLE) is a complex disease targeting multiple organs as a result of overactivation of the type I interferon (IFN) system, a feature currently being targeted by multiple biologic therapies against IFN-α. We have identified an estrogen-regulated microRNA, miR-302d, whose expression is decreased in SLE patient monocytes and identify its target as interferon regulatory factor (IRF)-9, a critical component of the transcriptional complex that regulates expression of interferon-stimulated genes (ISGs). In keeping with the reduced expression of miR-302d in SLE patient monocytes, IRF9 levels were increased, as was expression of a number of ISGs including MX1 and OAS1. In vivo evaluation revealed that miR-302d protects against pristane-induced inflammation in mice by targeting IRF9 and hence ISG expression. Importantly, patients with enhanced disease activity have markedly reduced expression of miR-302d and enhanced IRF9 and ISG expression, with miR-302d negatively correlating with IFN score. Together these findings identify miR-302d as a key regulator of type I IFN driven gene expression via its ability to target IRF9 and regulate ISG expression, underscoring the importance of non-coding RNA in regulating the IFN pathway in SLE.