Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study).

BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

Validation of the regret coping scale for healthcare professionals (RCS-HCP) in portuguese for Brazil

Introduction: assessing the ability to cope with regret can contribute to support strategies for health professionals. However, in Brazil only few instruments evaluate this ability in general. Objective: this study aimed was to adapt and validate the Regret Coping Scale for Healthcare Professionals (RCS-HCP) to Brazilian Portuguese . Methods: the instruments were translated, and the psychometric properties evaluated for validity and reliability. Three hundred and forty-one professionals participated, with an average age of 38.6 ± 9.2, and 87 participated in a retest survey 30 days later. Results: exploratory factor analysis showed adequacy of the structure (KMO = 0.786) composed of three factors. In the confirmation, the performance was close to acceptable. Reliability was good for the maladaptive strategies (α = 0.834) and adequate for the problem-focused initiatives (α = 0.717), but slightly too low for adaptive strategies (α = 0.595). Test- retest showed lower than expected values, with a Spearman- Brown coefficient of 0.703. Conclusion: the RCS-HCP scale showed satisfactory performance in relation to the properties evaluated.

Introdução: a avaliação da capacidade de lidar com o arrependimento pode contribuir para estratégias de apoio aos profissionais de saúde. No entanto, no Brasil existem poucos instrumentos que avaliam essa habilidade no contexto geral. Objetivo: o objetivo do estudo foi adaptar e validar a Regret Coping Scale for Healthcare Professionals (RCS-HCP) para profissionais de saúde brasileiros. Método: na validação, os instrumentos foram traduzidos e as propriedades psicométricas avaliadas quanto à validade e confiabilidade. Participaram 341 profissionais, com média de idade de 38,6 ± 9,2, e 87 participaram de uma pesquisa de reteste 30 dias depois. Resultados: a análise fatorial exploratória mostrou adequação da estrutura (KMO = 0,786) composta por três fatores. Na confirmação, o desempenho ficou próximo do aceitável. A confiabilidade foi boa para as estratégias mal adaptativas (α = 0,834) e adequada para as estratégias focadas no problema (α = 0,717), mas um pouco baixa demais para as estratégias adaptativas (α = 0,595). Teste-reteste apresentou valores abaixo do esperado, com coeficiente de Spearman-Brown de 0,703. Conclusão: a escala RCS-HCP apresentou desempenho satisfatório em relação às propriedades avaliadas.

Management of giant-cell arteritis in Switzerland: an online national survey.

AIMS OF THE STUDY: To assess current practices in diagnosing, treating, and following-up giant-cell arteritis by specialists in Switzerland and to identify the main barriers to using diagnostic tools. METHODS: We performed a national survey of specialists potentially caring for patients with giant-cell arteritis. The survey was sent by email to all members of the Swiss Societies of Rheumatology and for Allergy and Immunology. A reminder was sent to nonresponders after 4 and 12 weeks. Its questions covered the following dimensions: respondents' main characteristics, diagnosis, treatment, and imaging's role during follow-up. The main study results were summarized using descriptive statistics. RESULTS: Ninety-one specialists, primarily aged 46-65 years (n = 53/89; 59%), working in academic or nonacademic hospitals or private practice, and treating a median of 7.5 (interquartile range [IQR]: 3-12) patients with giant-cell arteritis per year participated in this survey. Ultrasound of temporal arteries/large vessels (n = 75/90; 83%) and positron-emission-tomography-computed tomography (n = 52/91; 57%) or magnetic resonance imaging (n = 46/90; 51%) of the aorta/extracranial arteries were the most common techniques used to diagnose giant-cell arteritis with cranial or large vessel involvement, respectively. Most participants reported a short time to obtain imaging tests or arterial biopsy. The glucocorticoid tapering scheme, glucocorticoid-sparing agent, and glucocorticoid-sparing treatment duration varied among the participants. Most physicians did not follow a predefined repeat imaging scheme for follow-up and mainly relied on structural changes (vascular thickening, stenosis, or dilatation) to drive treatment choice. CONCLUSIONS: This survey indicates that imaging and temporal biopsy are rapidly accessible for diagnosing giant-cell arteritis in Switzerland but highlights heterogeneous practice in many disease management areas.

Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration.

BACKGROUND: JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. METHODS: In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. RESULTS: We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. CONCLUSION: The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.

Portuguese validation of the Regret Intensity Scale (RIS-10) for measuring the intensity of regret associated with the provision of attention in health / Validación al portugués de la Escala de Intensidad de Arrepentimiento (RIS-10) para medir la intensidad del arrepentimiento asociado a la prestación de atención en salud / Validação da versão em português da escala Regret Intensity Scale (RIS-10) para medir a intensidade do arrependimento associada à prestação de atenção em saúde

Objective. The aim of the study was to adapt and validate the Regret Intensity Scale-10 (RIS-10) for Brazilian health professionals. Methods. The validation study took place in two phases, in which the first was the translation of the instruments and the second, the field validation using psychometric properties validity and reliability of the scale with 341 professionals (doctors, nurses and physiotherapists) linked to hospitals. Validity was assessed using content validities (six judges evaluation), criteria (correlation with the Life Satisfaction Scale - SWLS and Self-Reporting Questionnaire 20 -SRQ-20) and construct (exploratory analysis using the rotation method Promax, based on the slope graph and the Kaiser criterion and confirmatory using the structural equation model) after applying the questionnaire to professionals.Reliability was measured by Cronbach's α coefficient and retest test over a maximum period of 30 days. Reproducibility was calculated by intraclass correlation. Results. A total of 341 professionals participated, with an average age of 38.6 ± 9.2 years. The content validity index (CVI) was 1.00, for all items of the scale in the proportion of agreement of the judges. Exploratory factor analysis showed a satisfactory correlation (Kaiser-Meyer-Olkin = 0.88), suggesting a two-factor model, which comprises the main components of the emotion of regret (Factor I ­ emoticons, Factor II - feelings), accounting for 64% of the total variation of the first factor. In the confirmation, the index standardized root mean squared residual = 0.063 was close to the acceptable and other values were below. The scale correlated positively with SRQ-20 (p < 0.001) and negatively with SLWS (p = 0.003). Reliability showed (Cronbach's α = 0.863) and test­retest reliability showed lower values than expected. The Bland-Altman graph showed a mean bias of -1.5 with lower and upper limits of 15.8 to 12.8 respectively. Conclusion. The RIS-10 adapted for the population performed adequately in the psychometric properties evaluated for the assessment of the intensity of regret related to the provision of health care.

Objetivo. Adaptar y validar la Escala de Intensidad de Arrepentimiento-10 (RIS-10) para profesionales de la salud brasileños. Métodos. Este estudio de validación se realizó en dos fases: la primera fue la traducción de los instrumentos y la segunda, la validación de campo evaluando las propiedades psicométricas de validez y confiabilidad de la escala con 341 profesionales (médicos, enfermeras y fisioterapeutas) vinculados a hospitales. La validez se evaluó mediante la validez de contenido (evaluación de seis jueces), criterios (correlación con la Escala de Satisfacción de Vida - SWLS y Self-Reporting Questionnaire 20 -SRQ-20) y constructo (análisis exploratorio mediante el método de rotación Promax, basado en el gráfico de pendiente (Criterio de Kaiser y confirmatorio por el modelo de ecuación estructural) luego de aplicar el cuestionario a los profesionales. La confiabilidad se midió mediante el coeficiente α de Cronbach y la prueba de reprueba en un período máximo de 30 días. La reproducibilidad se calculó por correlación intraclase. Resultados. Participaron 341 profesionales, con una edad media de 38.6 ± 9.2 años. El índice de validez de contenido (IVC) fue de 1.00 para todos los ítems de la escala en proporción de acuerdo con los jueces. El análisis factorial exploratorio mostró una correlación satisfactoria (Kaiser-Meyer-Olkin = 0.88), sugiriendo un modelo de dos factores, que comprende los componentes principales de la emoción de arrepentimiento (Factor I - emociones, Factor II - sentimientos), correspondiente al 64% de la variación total del primer factor. Tras la confirmación, el índice cuadrático medio residual estandarizado = 0.063 estuvo cerca de ser aceptable y los otros valores estaban por debajo. La escala se correlacionó positivamente con SRQ-20 (p<0.001) y negativamente con SLWS (p = 0.003). La confiabilidad mostró un α de Cronbach = 0.863 y la confiabilidad test-retest mostró valores más bajos de lo esperado. El gráfico de Bland-Altman mostró un sesgo medio de -1.5 con límites inferior y superior de 15.8 a 12.8, respectivamente. Conclusión. El RIS-10 adaptado a la población mostró un desempeño adecuado en las propiedades psicométricas utilizadas para evaluar la intensidad del arrepentimiento relacionado con la prestación de atención a la salud.

Objetivo. O objetivo do estudo foi adaptar e validar a Regret Intensity Scale-10 (RIS-10) para profissionais de saúde brasileiros. Métodos. O estudo de validação ocorreu em duas fases, sendo a primeira a tradução dos instrumentos e a segunda, a validação de campo utilizando as propriedades psicométricas validade e confiabilidade da escala com 341 profissionais (médicos, enfermeiros e fisioterapeutas) vinculados a hospitais. A validade foi avaliada por meio de validades de conteúdo (avaliação de seis juízes), critérios (correlação com a Escala de Satisfação de Vida - SWLS e Self-Reporting Questionnaire 20 -SRQ-20) e construto (análise exploratória usando o método de rotação Promax, com base no gráfico de inclinação e critério de Kaiser e confirmatório pelo modelo de equações estruturais) após aplicação do questionário aos profissionais. A confiabilidade foi medida pelo coeficiente α de Cronbach e teste de reteste em um período máximo de 30 dias. A reprodutibilidade foi calculada por correlação intraclasse. Resultados. Participaram 341 profissionais, com média de idade de 38.6 ± 9.2 anos. O índice de validade de conteúdo (IVC) foi de 1,00, para todos os itens da escala na proporção de concordância dos juízes. A análise fatorial exploratória mostrou correlação satisfatória (Kaiser-Meyer-Olkin = 0.88), sugerindo um modelo de dois fatores, que compreende os principais componentes da emoção de arrependimento (Fator I - emoções, Fator II - sentimentos), correspondendo a 64% da variação total do primeiro fator. Na confirmação, o índice raiz quadrada média residual padronizada = 0.063 ficou próximo do aceitável e os demais valores ficaram abaixo. A escala correlacionou-se positivamente com SRQ-20 (p <0.001) e negativamente com SLWS (p = 0.003). A confiabilidade apresentou (α de Cronbach = 0.863) e a confiabilidade teste-reteste apresentou valores menores do que o esperado. O gráfico de Bland-Altman mostrou um viés médio de -1.5 com limites inferior e superior de 15.8 a 12.8, respectivamente. Conclusão. O RIS-10 adaptado para a população apresentou desempenho adequado nas propriedades psicométricas avaliadas para avaliação da intensidade do arrependimento relacionado à prestação de cuidados de saúde

Comparative effectiveness of tocilizumab versus TNF inhibitors as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis after the use of at least one biologic disease-modifying antirheumatic drug: analyses from the pan-European TOCERRA register collaboration.

OBJECTIVE: To compare the effectiveness of tocilizumab (TCZ) and tumour necrosis factor (TNF) inhibitors (TNFi) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) after the use of at least one biologic DMARD (bDMARD). METHODS: We included patients with RA having used at least one bDMARD from 10 European registries. We compared drug retention using Kaplan-Meier and Cox models and Clinical Disease Activity Index (CDAI) change over time with mixed-effects models for longitudinal data. The proportions of CDAI remission and low disease activity (LDA) at 1 year were compared using LUNDEX correction. RESULTS: 771 patients on TCZ as monotherapy (TCZ mono), 1773 in combination therapy (TCZ combo), 1404 on TNFi as monotherapy (TNFi mono) and 4660 in combination therapy (TNFi combo) were retrieved. Crude median retention was higher for TCZ mono (2.31 years, 95% CI 2.07 to 2.61) and TCZ combo (1.98 years, 95% CI 1.83 to 2.11) than TNFi combo (1.37 years, 95% CI 1.30 to 1.45) and TNFi mono (1.31 years, 95% CI 1.18 to 1.47). In a country and year of treatment initiation-stratified, covariate-adjusted analysis, hazards of discontinuation were significantly lower among patients on TCZ mono or combo compared with patients on TNFi mono or combo, and TNFi combo compared with TNFi mono, but similar between TCZ mono and combo. Average adjusted CDAI change was similar between groups. CDAI remission and LDA rates were comparable between groups. CONCLUSION: With significantly longer drug retention and similar efficacy to TNFi combo, TCZ mono or combo are reasonable therapeutic options in patients with inadequate response to at least one bDMARD.

Trajectories in cigarette dependence as a function of anxiety: a multilevel analysis.

BACKGROUND: We assessed the association of anxiety with cigarette dependence over time, depending on smoking status (daily, occasional or ex-smoker); and the association of anxiety with (a) smoking cessation, (b) reduction, and (c) relapse. METHODS: A prospective Internet survey of 1967 ever smokers was assessed three times at 2 weeks interval, in 2007-2010. Cigarette dependence was assessed using the cigarette dependence scale. Predictors included time, smoking status (daily, occasional or ex-smoker) and anxiety. All measures were assessed at each time point. RESULTS: Dependence decreased over time (slope=-0.21, p<0.001), as did feeling prisoner of cigarettes (slope=-0.25, p<0.001). Both decreased faster between week 0 and week 2 then between week 2 and week 4 (slopes=0.25, and 0.13; p<0.01). Differences in anxiety across individuals were associated with dependence (slope=0.28, p=0.001), feeling prisoner of cigarettes (slope=0.38, p<0.001), cessation (OR=0.42, p<0.001), relapse (OR=1.81, p<0.01), but not with smoking reduction (OR=0.85, p=0.35). Change over time in anxiety (within individuals) was associated with dependence (slope=-0.11, p=0.04), nor feeling prisoner of cigarettes (slope=-0.21, p=0.02), predicted smoking cessation (OR=0.51, p<0.001), smoking reduction (OR=0.67, p=0.047), and relapse (OR=1.52, p=0.03). CONCLUSIONS: Cross-sectionally, cigarette dependence, feeling prisoner of cigarettes, and smoking cessation were associated with anxiety; whereas prospectively, smoking cessation, reduction, and relapse were predicted by state anxiety. Thus, anxiety is an important factor that is associated with smoking behavior. Implications for treatment are discussed.