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Enfermedades del Tejido Conjuntivo , Enfermedad de Raynaud , Acetamidas , Antihipertensivos/efectos adversos , Enfermedades del Tejido Conjuntivo/tratamiento farmacológico , Epoprostenol/uso terapéutico , Humanos , Isquemia/tratamiento farmacológico , Pirazinas , Enfermedad de Raynaud/tratamiento farmacológicoRESUMEN
AIMS: Novel therapies are needed for recurrent pericarditis, particularly when corticosteroid dependent and colchicine resistant. Based on limited data, interleukin-1 blockade with anakinra may be beneficial. The aim of this multicentre registry was to evaluate the broader effectiveness and safety of anakinra in a 'real world' population. METHODS AND RESULTS: This registry enrolled consecutive patients with recurrent pericarditis who were corticosteroid dependent and colchicine resistant and treated with anakinra. The primary outcome was the pericarditis recurrence rate after treatment. Secondary outcomes included emergency department visits, hospitalisations, corticosteroid use and adverse events. Among 224 patients (46 ± 14 years old, 63% women, 75% idiopathic), the median duration of disease was 17 months (interquartile range 9-33). Most patients had elevated C-reactive protein (91%) and pericardial effusion (88%). After a median treatment of 6 months (3-12), pericarditis recurrences were reduced six-fold (2.33-0.39 per patient per year), emergency department admissions were reduced 11-fold (1.08-0.10 per patient per year), hospitalisations were reduced seven-fold (0.99-0.13 per patient per year). Corticosteroid use was decreased by anakinra (respectively from 80% to 27%; P < 0.001). No serious adverse events occurred; adverse events consisted mostly of transient skin reactions (38%) at the injection site. Adverse events led to discontinuation in 3%. A full-dose treatment duration of over 3 months followed by a tapering period of over 3 months were the therapeutic schemes associated with a lower risk of recurrence. CONCLUSION: In patients with recurrent pericarditis, anakinra appears efficacious and safe in reducing recurrences, emergency department admissions and hospitalisations.
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Corticoesteroides/administración & dosificación , Colchicina/uso terapéutico , Resistencia a Medicamentos , Factores Inmunológicos/administración & dosificación , Proteína Antagonista del Receptor de Interleucina 1/administración & dosificación , Pericarditis/tratamiento farmacológico , Adolescente , Corticoesteroides/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Esquema de Medicación , Reducción Gradual de Medicamentos , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Proteína Antagonista del Receptor de Interleucina 1/efectos adversos , Masculino , Persona de Mediana Edad , Pericarditis/diagnóstico por imagen , Recurrencia , Sistema de Registros , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
Objectives: Scleroderma renal crisis is a rare but serious complication affecting 2%-15% of patients with systemic sclerosis. Despite treatment with angiotensin-converting enzyme inhibitors, outcomes for scleroderma renal crisis patients are still poor. The cellular signaling mechanisms in scleroderma renal crisis are not yet known. Mammalian target of rapamycin, comprised of the subunits mTORC1 and mTORC2, has been shown to be activated in vascular lesions of renal transplant patients with anti-phospholipid antibody syndrome. Given the similarities between the pathophysiology of scleroderma renal crisis and anti-phospholipid antibody syndrome, we hypothesized that the mammalian target of rapamycin pathway would also be activated in the renal vasculature of patients with scleroderma renal crisis. Methods: We retrospectively analyzed renal biopsies of five patients with scleroderma renal crisis in the Canadian Scleroderma Research Group cohort. Immunostaining was performed using anti-P-S6RP antibodies to evaluate the phosphorylation of mTORC1, and anti-Rictor and anti-S473 to determine activation of mTORC2. Results: Four of the five patients showed mTORC1 activation in arteriolar endothelial cells, and three of the five patients showed mTORC1 activation in the arterial endothelial cells. Two of four samples showed Rictor expression in the arteriolar and arterial endothelial cells, showing mTORC2 activation. There was no expression of mTORC1 or mTORC2 in samples from two healthy controls. Conclusion: We demonstrate that both mTORC1 and mTORC2 are activated in renal biopsies with typical histologic features of scleroderma renal crisis. Dual mammalian target of rapamycin inhibitors are currently available and in development. These findings could inform further research into novel treatment targets for scleroderma renal crisis.
RESUMEN
This study was designed to estimate the burden of care that would be placed on rheumatologists to undertake cardiovascular (CV) risk assessment of traditional CV risk factors in their patients. This cross-sectional study was set in a rheumatology ambulatory clinic of a tertiary care, university hospital. Consecutive rheumatoid arthritis (RA) patients were recruited over 6 weeks and matched 1:1 on age and sex to patients with non-inflammatory problems who presented to the same clinic. CV risk was calculated using the Framingham Risk Score. We recruited 68 RA patients and 64 controls. The distribution of CV risk factors in RA patients and controls was similar. Ten-year Framingham CV risk scores based on traditional risk factors were moderate and similar in RA patients and controls (13.7 and 14.3%, respectively). Nevertheless, the proportion of RA patients with a history of coronary artery disease was more than twice that of controls (13 versus 5%, respectively). Approximately 20% of RA patients and controls did not have a primary care physician. In rheumatology practice, the problem of elevated CV risk due to traditional risk factors is not unique to RA patients. The burden for rheumatologists of undertaking CV risk assessment in their clinic could be considerable. Rheumatologists should manage inflammatory disease and health services should be improved to ensure the optimal management of traditional CV risk factors for all rheumatology patients.
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Artritis Reumatoide/epidemiología , Enfermedades Cardiovasculares/epidemiología , Reumatología/métodos , Reumatología/normas , Adulto , Anciano , Enfermedades Cardiovasculares/diagnóstico , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/epidemiología , Estudios Transversales , Femenino , Humanos , Inflamación , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVES: To adapt the self-administered comorbidity questionnaire (SCQ) into the Early Inflammatory Arthritis-SCQ (EIA-SCQ) and assess its clinimetric properties in EIA. METHODS: The EIA-SCQ and indices of disease activity, function, pain, health-related quality of life (HRQoL) and health resource utilization were administered to 320 patients with EIA. Twenty patients completed the EIA-SCQ a second time 1 week later. Construct validity was evaluated by testing the hypotheses that a valid comorbidity index would correlate well with age, weakly with HRQoL and recent resource utilization and poorly with indices of disease activity, function and pain. RESULTS: The intra-class correlation coefficient between repeat scores was 0.93 (95% CI 0.83-0.97). Kappa values for individual items ranged from 0.64 to 1.0. EIA-SCQ scores correlated moderately with age (Tau B = 0.29, P < 0.001) and weakly with function (HAQ-DI Tau B = 0.09, P = 0.03), pain (McGill Pain Questionnaire Tau B = 0.09, P = 0.05), some measures of HRQoL [the SF-36 mental component score (MCS) Tau B = - 0.08, P < 0.05; World Health Organization Disease Assessment Schedule II score Tau B = 0.09, P = 0.03] and a measure of resource utilization (number of tests in the last 4 months Tau B = 0.10, P = 0.04). The EIA-SCQ did not correlate with other measures of disease activity, another HRQoL measure [SF-36 physical component score (PCS)] or other measures of resource utilization. CONCLUSIONS: The EIA-SCQ is reliable and valid for use in EIA. It has the potential to become a useful measure of comorbidity in outcome studies of EIA when the resources for a full medical chart review are unavailable.
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Artritis/diagnóstico , Evaluación de la Discapacidad , Adulto , Anciano , Artritis/complicaciones , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Sensibilidad y Especificidad , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To assess the longitudinal relationships, including directionality, among chronic pain, symptoms of depression, and disease activity in patients with early inflammatory arthritis (EIA). METHODS: One hundred eighty patients with EIA completed an examination, including swollen joint count, and were administered the Center for Epidemiological Studies Depression Scale (CES-D) and the McGill Pain Questionnaire (MPQ) at 2 timepoints 6 months apart. Cross-lagged panel path analysis was used to simultaneously assess concurrent and longitudinal relationships among pain, symptoms of depression, and number of swollen joints. RESULTS: Pain, symptoms of depression, and number of swollen joints decreased over time (p < 0.001) and were prospectively linked to pain, symptoms of depression, and number of swollen joints, respectively, at 6 months. Symptoms of depression and pain were correlated with each other at baseline (0.47) and at 6-month followup assessments (0.28). Baseline symptoms of depression significantly predicted pain symptoms at 6 months (standardized regression coefficient = 0.28, p = 0.001), whereas pain and disease activity did not predict the course of any other variable after controlling for baseline values. CONCLUSION: Symptoms of depression predicted the trajectory of pain from baseline to 6 months. In addition, there were reciprocal/bidirectional associations between pain and symptoms of depression over time. More research is needed to better understand the relationship between pain and depressive symptoms and how to best manage patients with EIA who have high levels of both.
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Artritis Reumatoide/complicaciones , Artritis Reumatoide/psicología , Trastorno Depresivo/diagnóstico , Dimensión del Dolor/métodos , Dolor Intratable/complicaciones , Dolor Intratable/psicología , Adulto , Anciano , Artritis Reumatoide/fisiopatología , Causalidad , Enfermedad Crónica/psicología , Trastorno Depresivo/etiología , Evaluación de la Discapacidad , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Dolor Intratable/fisiopatología , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Estadística como AsuntoRESUMEN
OBJECTIVE: To assess the clinimetric properties of a new health-related quality of life (HRQOL) instrument, the World Health Organization Disability Assessment Schedule II (WHODAS II), in patients with early inflammatory arthritis. METHODS: Internal consistency as well as criterion, construct, and discriminative validity of the WHODAS II were assessed in 172 patients with early inflammatory arthritis who completed the WHODAS II, the Medical Outcomes Study Short Form 36 (SF-36), and other measures of disease severity, functioning, pain, depression, and resource use. Test-retest reliability of the WHODAS II was assessed by having a subset of 20 patients complete the WHODAS II a second time, 1 week after the first assessment. RESULTS: The WHODAS II had high internal consistency (Cronbach's alpha = 0.96 for patients working or in school and 0.93 for patients not working or in school). Test-retest intraclass correlation coefficients of the WHODAS II total score and subscales ranged from 0.82-0.96. The WHODAS II total score was strongly correlated with the SF-36 physical component score (Kendall's tau-b 0.51, P < 0.001) and moderately correlated with the SF-36 mental component score (tau-b 0.43, P < 0.001). WHODAS II correlations with disease outcomes ranged from Kendall's tau-b 0.15-0.55. The WHODAS II significantly differentiated between every aspect of disease severity assessed with the exception of measures of health resource use. CONCLUSION: The WHODAS II is a valid and reliable measure of HRQOL in cross-sectional studies of patients with early inflammatory arthritis. Research is still required to investigate potential item redundancy and determine its usefulness in longitudinal studies.