Predictors of serious infections in rheumatoid arthritis-a prospective Brazilian cohort.

BACKGROUND: Infections increase mortality and morbidity and often limit immunosuppressive treatment in rheumatoid arthritis patients. OBJECTIVE: To analyze the occurrence of serious infections and the associated factors in a cohort of rheumatoid arthritis patients under real-life conditions. METHODS: We analyzed data from the REAL, a prospective observational study, that evaluated Brazilian RA patients, with clinical and laboratory data collected over a year. Univariate and multivariate analyses were performed from the adjustment of the logistic regression model Generalized Estimating Equations (GEE), with the primary outcome being the occurrence of serious infection, defined as need for hospitalization or use of intravenous antibiotics for its treatment. RESULTS: 841 patients were included with an average follow-up time of 11.2 months (SD 2.4). Eighty-nine serious infections occurred, corresponding to 13 infections per 100 patient-years. Pulmonary fibrosis, chronic kidney disease (CKD) and central nervous system disease increased the chances of serious infection by 3.2 times (95% CI: 1.5-6.9), 3.6 times (95% CI: 1.2-10.4) and 2.4 times (95% CI: 1.2-5.0), respectively. The use of corticosteroids in moderate doses increased the chances by 5.4 times (95% CI: 2.3-12.4), and for each increase of 1 unit in the health assessment questionnaire (HAQ), the chance increased 60% (95% CI: 20-120%). CONCLUSION: The use of corticosteroids at moderate doses increased the risk of serious infection in RA patients. Reduced functionality assessed by the HAQ and comorbidities were other important factors associated with serious infection in this cohort.

Extra-articular manifestations of rheumatoid arthritis remain a major challenge: data from a large, multi-centric cohort.

INTRODUCTION: Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. OBJECTIVE: To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. METHOD: Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann-Whitney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). RESULTS: 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) ('p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. CONCLUSIONS: ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.

Extra-articular manifestations of rheumatoid arthritis remain a major challenge: data from a large, multi-centric cohort

Abstract Introduction Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. Objective To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. Method Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann-Whit-ney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). Results 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) ('p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. Conclusions ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.

Gout treatment: survey of Brazilian rheumatology residents.

To assess the current practices in gout management among Brazilian rheumatology residents. We performed a cross-sectional online survey among all the rheumatology residents and those rheumatologists who had just completed their training (post-residency (PR)) regarding their approach to gout management. Results were compared with the 2012 American College of Rheumatology (ACR) gout guidelines and with the responses of a previous survey with a representative sample of practicing Brazilian rheumatologists (RHE). We received 224 responses (83%) from 271 subjects. Among all respondents, the first-choice treatment for gout flares was the combination of a nonsteroidal anti-inflammatory drug + colchicine for otherwise healthy patients. A target serum urate <6 mg/dL for patients without tophi was reported by >75%. Less than 70% reported starting allopurinol at low doses (≤100 mg/day) for patients with normal renal function and <50% reported maintaining urate-lowering therapy indefinitely for patients without tophi. Among residents and PR, the residency stage was the main predictor of concordance with the ACR guidelines, with PR achieving the greatest rates. Reported practices were commonly concordant with the 2012 ACR gout guidelines, especially among PR. However, some important aspects of gout management need improvement. These results will guide the development of a physician education program to improve the management of gout patients in Brazil.

Muito além do trauma: uma investigação sobre o papel das reações peritraumáticas sobre o transtorno de estresse pós-traumático / Beyond the trauma: an investigation of the role of peritraumatic reactions on posttraumatic stress disorder

O Transtorno de Estresse Pós-Traumático (TEPT) é uma condição debilitante que impacta significativamente a qualidade de vida dos seus portadores. Dentre vários fatores de risco para o TEPT, as reações peritraumáticas (RP), como a imobilidade tônica peritraumática (ITP), dissociação (DP) e reações físicas de pânico (RFP), estão entre as mais investigadas. No entanto, a maioria dos estudos avaliou essas RP separadamente, e o elo entre elas e o TEPT ainda não foi bem compreendido. Portanto, essa tese teve como objetivos: (i) estimar simultaneamente o efeito das três RP sobre o TEPT utilizando um instrumento validado; e (ii) avaliar se há efeito indireto da ITP sobre o TEPT mediado pelo sentimento de culpa/vergonha. Utilizamos modelagem de equações estruturais para analisar dados de 3211 participantes do Rio de Janeiro e de São Paulo. Tratamos as RP como variáveis latentes, selecionando desconfundidores específicos para cada reação. Nossas exposições foram as RP, sendo TEPT o desfecho. Calculamos odds ratios e intervalos de confiança de 95%. Utilizamos o Bayesian Information Criterion para comparar o ajuste de modelos não aninhados. Quando analisadas separadamente, todas as RP alcançaram significância estatística. No entanto, apenas DP (ORDP=1,8; IC95%:1,3-2,4) e RFP (ORRFP=2,5; IC95%:1,8-3,4) permaneceram estatisticamente significativas quando incluímos as três reações em um modelo com seus respectivos desconfundidores e correlações entre elas. Os resultados sugeriram um possível efeito da ITP sobre o TEPT (ORITP=1,4; IC95%:1,0-1,9). As interações entre as RP não foram estatisticamente significativas. Ao investigarmos o sentimento de culpa/vergonha como mediador entre ITP e TEPT, o efeito indireto alcançou apenas significância estatística limítrofe (ORITP(TNIE)=1,1; IC95%:1,0-1,2). Os efeitos direto (ORITP(PNDE)=1,3; IC95%: 0,8-1,8) e total (ORITP(TE)=1,4; IC95%:0,9-1,9) para ITP perderam significância quando todas as RP, seus desconfundidores e correlações entre elas fizeram parte do mesmo modelo. As demais RP, no entanto, permaneceram estatisticamente significativas (ORDP=1,7; IC95%:1,3-2,3 e ORRFP=2,5; IC95%:1,8-3,4). Nossos resultados mostraram que a DP e as RFP aumentaram o risco de TEPT mesmo quando consideradas em conjunto. A ITP pode ter efeito sobre o risco de TEPT, mas esse achado deve ser interpretado com cautela devido a significância limítrofe dessa RP em nosso modelo final. Também não identificamos uma mediação significativa entre ITP e TEPT pelos sentimentos de culpa/vergonha. Contudo, a significância limítrofe encontrada para o efeito indireto demanda investigações adicionais. Nossos achados reforçam a ideia de que as reações peritraumáticas devem ser analisadas e compreendidas como ocorrências simultâneas. Também seria oportuno que estudos envolvendo culpa/vergonha, ITP e TEPT focalizassem traumas caracterizados por aprisionamento e impossibilidade de escapar, dado que estas experiências são apontadas como mais susceptíveis para desencadear a ITP. (AU)

Posttraumatic stress disorder (PTSD) is a debilitating condition that greatly impacts quality of life. Among several PTSD risk factors, peritraumatic reactions (PR) such as peritraumatic tonic immobility (PTI), dissociation (PD) and physical panic reactions (PPR) are some of the most investigated. However, several studies have assessed these PR separately, and the pathway connecting them to PTSD is not well understood. Therefore, this thesis aimed to: (i) simultaneously estimate the effect of the three PR on PTSD using a validated instrument; and (ii) assess if there is an indirect effect of PTI on PTSD mediated by feelings of guilt/shame. We used structural equation modelling to analyse data from 3211 participants from Rio de Janeiro and São Paulo. We treated the PR as latent variables and selected specific confounders for each reaction. Our exposures were the PR, and PTSD was the outcome. We calculated odds ratios and 95% confidence intervals for each analysis. We also employed the Bayesian Information Criterion to compare the goodness of fit between non-nested models. Separately, all PR achieved statistically significant results. However, only PD (ORPD=1.8; 95%CI:1.3-2.4) and PPR (ORPPR=2.5; 95%CI:1.8-3.4) remained statistically significant when all three were included in a model with their respective confounders and correlations among all PR. Our findings suggested a possible effect of PTI on PTSD (ORPTI=1.4; 95%CI:1.0-1.9). Interactions between the PR were not statistically significant. When we investigated feelings of guilt/shame as the mediator between PTI and PTSD, the indirect effect achieved a borderline statistical significance (ORPTI(TNIE)=1.1; 95%CI:1.0-1.2). Direct (ORPTI(PNDE)=1.3; 95%CI:0.8-1.8) and total (ORPTI(TE)=1.4; 95%CI:0.9-1.9) effects lost their significance when all PR, their confounders and correlations were included in the same model. The other PR remained statistically significant (ORPD=1.7; 95%CI:1.3-2.3 and ORPPR=2.5; 95%CI:1.8-3.4). Our findings showed PD and PPR to increase the risk of PTSD even when considered in tandem. PTI could have an effect on PTSD, but this must be considered cautiously, as this PR only reached borderline significance in our final model. Feelings of guilt/shame did not significantly mediate PTI's effect on PTSD. However, a borderline statistical significance in the indirect effects warrants further investigation. Our findings reinforce the hypothesis that peritraumatic reactions should be analysed and understood as simultaneous occurrences, not as separate entities. It would also be appropriate for studies concerning guilt/shame, PTI and PTSD to focus on traumas characterized by imprisonment and feelings of inescapability, given that these experiences are allegedly more likely to trigger PTI. (AU)

Análise da capacidade funcional de uma coorte brasileira de pacientes com artrite reumatoide / Functional capacity analysis in a Brazilian cohort of rheumatoid arthritis patients

A artrite reumatoide é uma doença inflamatória crônica com prevalência mundial estimada entre 0,5 e 1%, caracterizada por dor, edema e rigidez matinal nas articulações. A doença não controlada leva à destruição articular progressiva, causando perda da qualidade de vida e da capacidade funcional. A manutenção da capacidade envolve estar apto a realizar atividades básicas do cotidiano, envolvendo higiene pessoal, carregar objetos, vestir-se, alimentar-se e locomover-se. Limitações ou impossibilidade de realizar estas atividades implica em alguma incapacidade funcional - geralmente mensurada, na artrite reumatoide, por um dos componentes do Questionário de Avaliação de Saúde. Esta dissertação teve como objetivo geral analisar a variação da capacidade funcional medida pelo Questionário de Avaliação de Saúde ­ Índice de Incapacidade em pacientes com artrite reumatoide acompanhados ambulatorialmente por um ano e propor um modelo preditivo, em função de fatores sociodemográficos e clínicos. Os objetivos específicos foram: (i) avaliar quais variáveis, previamente reportadas na literatura, têm impacto sobre a capacidade funcional dos pacientes com artrite reumatoide de uma coorte nacional; (ii) construir um modelo preditivo próprio à realidade brasileira utilizando variáveis de fácil obtenção; e (iii) avaliar se há modificação de efeito pela interação entre atividade de doença e o tempo no estudo. Avaliamos 1111 pacientes com artrite reumatoide atendidos em 11 centros de referência para tratamento de doenças reumáticas vinculados ao Sistema Único de Saúde, com coleta de dados prospectiva. Utilizamos modelos lineares de efeitos mistos para avaliar a variação da capacidade funcional, mensurada pelo Questionário de Avaliação de Saúde ­ Índice de Incapacidade, nos dados coletados em três momentos ao longo de um ano. Esta análise revelou que, na população avaliada, sexo, status socioeconômico, dor articular, uso prévio de medicamentos imunobiológicos, atividade e tempo de doença estavam associados à variação da capacidade funcional, com capacidade explicativa de 37% de nosso modelo. Ao definir as variáveis a analisar a partir de um referencial teórico estruturado com a revisão de literatura, identificamos que nossos achados apresentaram pontos comuns com estudos realizados na Europa e América do Norte. Alguns destes achados foram: pior capacidade funcional em pacientes com mais dor e doença em atividade, em pacientes do sexo feminino e naqueles que tenham feito uso prévio de medicamento imunobiológico. Também foram relevantes as curvas em formato de J relacionadas com mais tempo de doença e pior status socioeconômico. Levantamos algumas hipóteses para os escores de incapacidade encontrados nesta população, como a adaptação dos pacientes às limitações com o avanço do tempo de doença e a percepção de que estas limitações seriam parte do envelhecimento normal. Apesar de construído a partir de uma população com mais de uma década de doença, nosso modelo incluiu variáveis comumente associadas ao componente reversível da incapacidade funcional, como dor e atividade de doença. Neste cenário, o melhor controle da doença traria benefícios aos pacientes, com recuperação de ao menos parte da capacidade funcional

Rheumatoid arthritis is an inflammatory chronic disease with estimated global prevalence of 0.5 ­ 1%, characterized by morning stiffness, joint pain and swelling. If not controlled, the disease leads to progressive joint destruction, decreasing quality of life and functional capacity. To maintain this capacity involves being able to perform basic daily life activities, such as those related with personal hygiene, to carry objects, to get dressed, to eat and to deambulate. Limitations or to be unable to perform these activities implies in at least some functional disability ­ usually measured, in rheumatoid arthritis patients, by one of the Health Assessment Questionnaire components. This dissertation's general aim was to analyze functional capacity variation, measured by the Health Assessment Questionnaire ­ Disability Index, in a Brazilian cohort of rheumatoid arthritis patients followed at outpatients clinics for a year and to create a predictive model as result of several demographic and clinical features. The specific aims were: (i) to evaluate which of the variables that were previously reported in the literature have impact on the functional capacity of RA patients in a Brazilian cohort; (ii) to build a predictive model adjusted to the Brazilian reality with variables of feasible acquisition; and (iii) to evaluate if there is effect modification due to the interaction between disease activity and length of time in the study. We evaluated 1111 rheumatoid arthritis patients followed at 11 reference treatment centers for rheumatic diseases, all pertaining to the Unified Health System ­ SUS, with prospective data collection. We applied linear mixed effects models to evaluate the variation in functional capacity, measured by Health Assessment Questionnaire ­ Disability Index, within the data collected at three time points along one year. This analysis revealed that, in the evaluated population, sex, socioeconomic status, joint pain, previous use of immunobiological drugs, disease duration and activity were associated with functional capacity variation, in a model with a 37% explanatory capacity. After defining which database variables to use from a theorical model structured with the literature review, we identified that our findings presented common aspects with studies from Europe and North America. A few of the findings were: decrease of functional capacity with pain and disease activity, in female patients and also in those with previously reported immunobiological use. Also relevant were the J-shaped curves related with longer disease duration and worse socioeconomic status. Some hypotheses for the functional capacity scores found were patient adaptability to physical limitations accrued with disease duration and perception that those limitations would be part of a normal ageing process. Though built with data from a population with more than a decade of disease duration, our model included variables commonly associated with the reversible component of functional disability, such as pain and disease activity. In this scenario, tighter control of disease activity would benefit patients and bring the possibility of regaining, at least partially, their functional capacity