RESUMEN
ATP1A3 encodes the α3 subunit of the sodium-potassium ATPase, one of two isoforms responsible for powering electrochemical gradients in neurons. Heterozygous pathogenic ATP1A3 variants produce several distinct neurological syndromes, yet the molecular basis for phenotypic variability is unclear. We report a novel recurrent variant, ATP1A3(NM_152296.5):c.2324C>T; p.(Pro775Leu), in nine individuals associated with the primary clinical features of progressive or non-progressive spasticity and developmental delay/intellectual disability. No patients fulfil diagnostic criteria for ATP1A3-associated syndromes, including alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism or cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss (CAPOS), and none were suspected of having an ATP1A3-related disorder. Uniquely among known ATP1A3 variants, P775L causes leakage of sodium ions and protons into the cell, associated with impaired sodium binding/occlusion kinetics favouring states with fewer bound ions. These phenotypic and electrophysiologic studies demonstrate that ATP1A3:c.2324C>T; p.(Pro775Leu) results in mild ATP1A3-related phenotypes resembling complex hereditary spastic paraplegia or idiopathic spastic cerebral palsy. Cation leak provides a molecular explanation for this genotype-phenotype correlation, adding another mechanism to further explain phenotypic variability and highlighting the importance of biophysical properties beyond ion transport rate in ion transport diseases.
Asunto(s)
Ataxia Cerebelosa , Discapacidad Intelectual , Humanos , Mutación/genética , Síndrome , Discapacidad Intelectual/genética , Ataxia Cerebelosa/genética , Fenotipo , Espasticidad Muscular/genética , Cationes , ATPasa Intercambiadora de Sodio-Potasio/genéticaRESUMEN
BACKGROUND: The objective of the present study is to describe the characteristics of interstitial pneumonia with autoimmune features (IPAF) patients, to assess the incidence rate of functional respiratory impairment over time and to evaluate the influence of therapeutic alternatives on the prognosis of these patients. METHODS: A longitudinal observational multicenter study was performed (NEREA registry). It was carried out by a multidisciplinary team in seven Hospitals of Madrid. Patients were included from IPAF diagnosis. MAIN OUTCOME: poor prognosis as functional respiratory impairment (relative decline in FVC % defined as ≥ 5% every 6 months). Covariates: therapy, sociodemographic, clinical, radiological patterns, laboratory and functional tests. STATISTICS: Survival techniques were used to estimate IR per 100 patients-semester with their 95% confidence interval [CI]. The influence of covariates in prognosis were analyzed through cox multivariate regression models (hazard ratio (HR) and [CI]). RESULTS: 79 IPAF were included, with a mean and a maximum follow-up of 3.17 and 12 years respectively. Along the study, 77.2% received treatment (52 glucocorticoids, 25 mycophenolate, 21 azathioprine, 15 rituximab and 11 antifibrotics). IR was 23.9 [19.9-28.8], and 50% of IPAF developed functional respiratory impairment after 16 months from its diagnosis. Multivariate analysis: usual interstitial pneumonia (UIP) had poorer prognosis compared to non-specific interstitial pneumonia (NSIP) (p = 0.001). In NSIP, positive ANA, increased the risk of poor prognosis. In UIP, glucocorticoids (HR: 0.53 [0.34-0.83]), age (HR: 1.04 [1.01-1.07]), and Ro-antibodies (HR: 0.36 [0.19-0.65]) influenced the prognosis. CONCLUSIONS: IPAF have functional impairment during the first years of disease. Factors predicting deterioration differ between radiographic patterns. Our real-life study suggests the potential benefit of particular therapies in IPAF.
Asunto(s)
Enfermedades Autoinmunes , Neumonías Intersticiales Idiopáticas , Fibrosis Pulmonar Idiopática , Enfermedades Pulmonares Intersticiales , Insuficiencia Respiratoria , Humanos , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/epidemiología , Neumonías Intersticiales Idiopáticas/diagnósticoRESUMEN
BACKGROUND: To assess mortality rate (MR) and standardized mortality rate (SMR) of rheumatoid arthritis-related interstitial lung disease (RA-ILD) patients and to evaluate the role of radiographic patterns in mortality. METHODS: A longitudinal multicentric study was conducted in RA-ILD patients from 2005 to 2015 and followed-up until October 2018 in Madrid. Patients were included in the Neumologia-Reumatología y Enfermedades Autoinmunes Registry, from diagnosis of ILD. The main outcome was all-cause mortality. The radiographic pattern at baseline [usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), or others] was the independent variable. Covariables included sociodemographic and clinical data. Survival techniques were used to estimate MR, expressed per 1000 persons-year with their 95% confidence intervals [CI]. Cox multiple regression model was run to examine the influence of radiographic patterns on survival. SMR [CI] was calculated comparing MR obtained with MR expected in the general population of Madrid by indirect age-gender standardization. RESULTS: 47 patients were included with a follow-up 242 patients-year. There were 16 (34%) deaths, and most frequent causes were acute ILD exacerbation and pneumonia. MR was 64.3 [39.4-104.9], and 50% of the patients died at 8.3 years from ILD diagnosis. After adjusting for confounders, (UIP compared to NSIP was associated with higher mortality risk. The overall SMR was 2.57 [1.4-4.17]. Women of 60-75 years of age were the group with the highest SMR. CONCLUSIONS: RA-ILD is associated with an excess of mortality compared to general population. Our results support that UIP increases the risk of mortality in RA-ILD, regardless other factors.
Asunto(s)
Artritis Reumatoide/complicaciones , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/patología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Enfermedades Pulmonares Intersticiales/etiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , España/epidemiología , Análisis de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: To asses the clinical course in RA-related interstitial lung disease (RA-ILD) patients with and without rituximab (RTX). The influence of other variables was also evaluated. METHODS: A longitudinal multicentre study was conducted in RA diagnosed with ILD from 2007 until 2018 in Madrid. Patients were included in a registry [pNEumology RhEumatology Autoinmune diseases (NEREA)] from the time of ILD diagnosis. The main endpoint was functional respiratory impairment (FI), when there was a decline ≥5% in the predicted forced vital capacity compared with the previous one. Pulmonary function was measured at baseline and in follow-up visits every 6-12 months. The independent variable was therapy with RTX. Covariables included sociodemographic, clinical, radiological and other therapies. Survival techniques were used to estimate the incidence rate (IR) and 95% CI of functional impairment, expressed per 100 patient-semesters. Cox multivariate regression models were run to examine the influence of RTX and other covariates on FI. Results were expressed as the hazard ratio (HR) and CI. RESULTS: A total of 68 patients were included. FI occurred in 42 patients [IR 23.5 (95% CI 19, 29.1)] and 50% of them had FI within 1.75 years of an ILD diagnosis. A multivariate analysis showed that RTX exposure resulted in a lower risk of FI compared with non-exposure [HR 0.51 (95% CI 0.31, 0.85)]. Interstitial pneumonia, glucocorticoids, disease activity and duration also influenced FI. CONCLUSION: RA-ILD patients deteriorate over time, with the median time free of impairment being <2 years. Patients exposed to RTX had a higher probability of remaining free of FI compared with other therapies. Other factors have also been identified.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/complicaciones , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Rituximab/uso terapéutico , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Enfermedades Pulmonares Intersticiales/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Resultado del Tratamiento , Capacidad VitalRESUMEN
OBJECTIVE: The aim of this study was to assess the reliability and validity of the Spanish version of the Rosser classification system for disease states in patients with musculoskeletal disorders. METHODS: Our study was based on a questionnaire validation design. Patients were attended at an outpatient rheumatology clinic at Hospital Clínico San Carlos, Madrid, Spain. The Rosser classification system was completed by the physician from the research team (PMQ) and by the patient (HMQ). Criterion standards: The EuroQol-5D for the HMQ and the physician global estimate (DOCGL) for the PMQ. Internal consistency reliability was assessed using Cronbach α. Test-retest reliability and interobserver reliability were analyzed using the intraclass correlation coefficient. The criterion validity between HMQ and EuroQol-5D and between PMQ and DOCGL was assessed using the Spearman correlation coefficient. RESULTS: The full analysis was based on 4 samples of patients (104 to 266 patients), most of whom were middle-aged women. For HMQ, Cronbach α was 0.70. Test-retest reproducibility was 0.7. With respect to criterion validity, significant correlations in the expected direction were observed. For PMQ, Cronbach α was 0.70, indicating excellent intraobserver and interobserver reliability. With respect to criterion validity, strong correlations were observed between the PMQ and the DOCGL. CONCLUSIONS: The Rosser classification system showed satisfactory reliability and suitable criterion validity for patients with musculoskeletal disorders. The instrument seems to be suitable for clinical decision making and research.
Asunto(s)
Calidad de Vida , Enfermedades Reumáticas/psicología , Encuestas y Cuestionarios , Adulto , Anciano , Femenino , Humanos , Lenguaje , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/fisiopatología , España , TraduccionesRESUMEN
OBJECTIVES: Biological DMARDs are widely used in the treatment of rheumatoid arthritis (RA) but their relationship with adverse drug reaction (ADR) is important. RA is now known to increase in incidence and prevalence with age. Our objective was to assess the incidence of severe ADR in the long term, compare safety between the different bDMARDs and identify other possible risk factors for severe ADR in elderly RA patients. METHODS: A 14-year retrospective longitudinal study was performed. RA patients followed in an out-patient clinic starting bDMARDs after the age of 65 were included. PRIMARY OUTCOME: discontinuation due to a severe ADR related to bDMARDs (etanercept, infliximab, adalimumab, rituximab, golimumab, certolizumab, abatacept and tocilizumab). Covariables: sociodemographic, clinical and therapy. Incidence rates of discontinuation were estimated using survival techniques and comparison between bDMARDs discontinuation rates and other associated factors were run by Cox regression models. RESULTS: We analysed 286 courses of bDMARDs therapy in 146 elderly patients (604 patient-years). 78% were women, with a mean age at diagnosis of 66.5±7 years, and a median time to the start of the first bDMARDs of 6±4 years. The incidence of discontinuation due to severe ADR estimated was 10.2% patient-years, with a median survival of around 7 years. The most frequent cause was infections. Etanercept had the lowest risk of severe ADR compared to other bDMARDs. CONCLUSIONS: Our study reflects the 'real world' experience in elderly RA patients on bDMARDs, with non-selected patients for a 14-year follow-up.
Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Factores de Edad , Anciano , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/inmunología , Femenino , Humanos , Huésped Inmunocomprometido , Incidencia , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Análisis Multivariante , Infecciones Oportunistas/epidemiología , Infecciones Oportunistas/inmunología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , España/epidemiología , Resultado del TratamientoRESUMEN
OBJECTIVES: To assess the incidence and the risk of relapses in giant cell arteritis (GCA) patients treated with and without methotrexate (MTX) in clinical practice. Other associated factors were also investigated. METHODS: An inception cohort of GCA was assembled in the out-patient clinic at Hospital Clínico San Carlos, including patients from the date of diagnosis (Jan-1991 until Sept-2013), and followed-up until lost of follow up or Sept-2014. MAIN OUTCOME: relapse defined as recurrence of symptoms or signs of GCA with high ESR and the need to increase glucocorticoids at least 10mg over the previous dose. The independent variable was exposure to MTX over time. Covariables: Sociodemographic, clinical, and treatment. Incidence rates of relapses (IR) per 100 patient-year with their 95% confidence intervals [CI] were estimated using survival techniques. MTX influence on relapses was analysed by Cox models. RESULTS: 168 patients were included (675 patient-year). 31% of patients had relapses (IR of 12 [9.6-14.9]), and the median number of relapses was 1[1-2]. 65% of the patients were on MTX, (mean dose: 10mg). In the bivariate analysis, the risk of relapses in patients with and without MTX did not achieve statistical signification (p=0.1). After adjusting in the multivariate analysis, exposure to MTX had 72% less risk of relapse compared to those without MTX (p<0.05). Other variables included in the final model were: visual alterations and malaise at clinical presentation of GCA. CONCLUSIONS: The use of MTX seems to decrease the risk of recurrences. We also found other factors influencing on relapses.
Asunto(s)
Antirreumáticos/uso terapéutico , Arteritis de Células Gigantes/tratamiento farmacológico , Metotrexato/uso terapéutico , Anciano , Anciano de 80 o más Años , Sedimentación Sanguínea , Quimioterapia Combinada , Femenino , Arteritis de Células Gigantes/sangre , Glucocorticoides/administración & dosificación , Humanos , Incidencia , Masculino , Análisis Multivariante , Modelos de Riesgos Proporcionales , Recurrencia , RiesgoRESUMEN
OBJECTIVES: To assess the long-term continuation of methotrexate (MTX) in a cohort of patients with giant cell arteritis (GCA) in daily clinical practice. Factors associated with its discontinuation rate were also investigated. METHODS: A longitudinal study from 1991-2014, was performed. GCA patients with MTX and followed-up in a rheumatology outpatient clinic of Madrid during the study period were included. PRIMARY OUTCOME: discontinuation of MTX due to: adverse drug reactions (ADR moderate and severe); inefficacy; sustained clinical response; patient decision. Covariables: sociodemographic, clinical and therapy. Incidence rates (IR) of MTX discontinuation per 100 patient-years with their 95% confidence interval (CI) were estimated using survival techniques. Factors associated to specific discontinuation causes were analysed using Cox models. RESULTS: We included 108 patients (244 patient-years). The IR was 37.2 [30.3-45.7]. The IR due to ADR, severe ADR, sustained clinical response and inefficacy was 20.8 [15.8-27.4]; 5.7 [3.3-9.6]; 8.2 [5.3-12.7] and 2.8 [1.3-6.0], respectively. Regarding multivariate analysis, younger patients, baseline cardiovascular disease, taking more glucocorticoids and lower initial doses of MTX were associated to a higher discontinuation rate due to inefficacy. Factors influencing the suspension due to ADRs were: older age, baseline. Chronic obstructive pulmonary disease, higher baseline erythrocyte sedimentation rate, several specific clinical patterns at diagnosis, and higher maximum dose of MTX during the follow up. In the final model for sustained clinical response older patients and more recurrences were independently associated to less discontinuation rate. CONCLUSIONS: We provide further data of the potential safety of long-term MTX in the management of GCA. We have also found several factors influencing the continuation of MTX.
Asunto(s)
Arteritis de Células Gigantes/tratamiento farmacológico , Inmunosupresores/administración & dosificación , Metotrexato/administración & dosificación , Comorbilidad , Esquema de Medicación , Interacciones Farmacológicas , Arteritis de Células Gigantes/diagnóstico , Arteritis de Células Gigantes/inmunología , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Estimación de Kaplan-Meier , Estudios Longitudinales , Metotrexato/efectos adversos , Análisis Multivariante , Seguridad del Paciente , Modelos de Riesgos Proporcionales , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , España , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVES: To describe and compare dosing optimisation in biological DMARDs (bDMARDs) and relapses after that, in a cohort of rheumatoid arthritis (RA) during clinical practice. METHODS: Observational retrospective longitudinal study of RA patients taking bDMARDs from December 1999 to November 2013. Optimisation was defined as a 15% decrease in dose either reducing single dose or separating dose interval administration, for at least 4 times the recommended period between dosages. Relapse was defined as suspension or starting again with the recommended dose after optimisation. Incidence rates (IR) per 100 patient-years were estimated using survival techniques. Cox multivariate models were conducted to compare bDMARDs expressed in hazard ratios (HR) and confidence intervals [95%CI]. RESULTS: 443 patients and 752 different courses of bDMARDs treatments were included. We observed 146 optimisations with an IR of 8.1. The HR of optimisation in: a) adalimumab, etanercept and rituximab compared to infliximab was 1.56 [1.01-2.4], 1.5 [0.9-2.4] and 0.6 [0.3-1.4], respectively; b) adalimumab, etanercept compared to rituximab were 2.3 [1.2-4.5] and 2.2 [1.2-4.3]. There were no statistically significant differences between adalimumab and etanercept. Following optimisation, 36% relapsed (78% due to disease activity). The IR related to disease activity was 6.3, and was lower for adalimumab and etanercept compared to infliximab (HR: 0.42; [0.19-0.94]; HR: 0.34; [0.13-0.89], respectively). There were no statistically significant differences between etanercept and adalimumab. No patients on rituximab relapsed. CONCLUSIONS: Optimisation was similar between adalimumab and etanercept, and was lower for infliximab and rituximab. After optimisation, rituximab did not relapse, but infliximab did with the highest hazard.
Asunto(s)
Antirreumáticos/administración & dosificación , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/administración & dosificación , Cálculo de Dosificación de Drogas , Adulto , Anciano , Antirreumáticos/efectos adversos , Artritis Reumatoide/diagnóstico , Productos Biológicos/efectos adversos , Esquema de Medicación , Femenino , Humanos , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoAsunto(s)
Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Progresión de la Enfermedad , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/etiología , Sistema de Registros , Rituximab/uso terapéuticoRESUMEN
OBJECTIVES: To describe the epidemiological and clinical characteristics of an outbreak of occupational silicosis and the associated working conditions. METHODS: Cases were defined as men working in the stone cutting, shaping, and finishing industry in the province of Cádiz, diagnosed with silicosis between July 2009 and May 2012, and were identified and diagnosed by the department of pulmonology of the University Hospital of Puerto Real (Cádiz). A census of workplaces using quartz conglomerates was carried out to determine total numbers of potentially exposed workers. A patient telephone survey on occupational exposures and a review of medical records for all participants were conducted. RESULTS: Silicosis was diagnosed in 46 men with a median age of 33 years and a median of 11 years working in the manufacturing of countertops. Of these cases, 91.3% were diagnosed with simple chronic silicosis, with an abnormal high-resolution computerized tomography (HRCT) scan. One patient died during the study period. Employer non-compliance in prevention and control measures was frequently reported, as were environmental and individual protection failures. CONCLUSIONS: The use of new construction materials such as quartz conglomerates has increased silicosis incidence due to intensive occupational exposures, in the context of high demand fuelled by the housing boom. This widespread exposure poses a risk if appropriate preventive measures are not undertaken.
Asunto(s)
Industria de la Construcción , Brotes de Enfermedades , Exposición Profesional , Cuarzo/toxicidad , Silicosis/epidemiología , Adulto , Industria de la Construcción/métodos , Humanos , Incidencia , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Prevalencia , Pruebas de Función Respiratoria , Silicosis/diagnóstico , Silicosis/etiología , España/epidemiología , Encuestas y Cuestionarios , Tomografía Computarizada por Rayos XRESUMEN
To evaluate a rheumatology outpatient consultation access system for new patients. New patients seen from April 2005 to April 2006 at our rheumatology clinic (n = 4,460) were included and classified according to their appointment type: ordinary appointments (OA) to be seen within 30 days, urgent appointments (UA) and work disability appointments (WDA) to be seen within 3 days. Age, sex, diagnosis, and health-related quality of life (HRQoL) as determined by the Rosser Index were recorded. Logistic regression models were run to identify factors that contribute to each type of appointment. OA was the method of access for 1,938 new patients, while 1,194 and 1,328 patients were seen through WDA and UA appointments, respectively. Younger male patients, and those with microcrystalline arthritis, sciatica, shoulder, back, or neck pain, were more likely to use the faster access systems (UA or WDA), whereas patients with a degenerative disease were mainly seen through OA (<0.001). Subjects with poor (3.96; 95 % CI, 2.8-5.5) or very poor HRQoL (70.8; 95 % CI, 14.9-334) were strongly associated to visiting a rheumatologist through the WDA or UA access systems, respectively, compared to OA. Age, gender, diagnosis, and mainly health-related quality of life are associated with the referral pattern of access to rheumatologic outpatient care. Among new patients subjects with the worst HRQoL were more likely to access with faster methods (UA or WDA) than those with better HRQoL.
Asunto(s)
Atención Ambulatoria/normas , Accesibilidad a los Servicios de Salud/normas , Enfermedades Profesionales/diagnóstico , Indicadores de Calidad de la Atención de Salud/normas , Calidad de Vida , Derivación y Consulta/normas , Enfermedades Reumáticas/diagnóstico , Reumatología/normas , Adulto , Factores de Edad , Anciano , Citas y Horarios , Distribución de Chi-Cuadrado , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/psicología , Oportunidad Relativa , Pautas de la Práctica en Medicina/normas , Valor Predictivo de las Pruebas , Enfermedades Reumáticas/psicología , Factores Sexuales , España , Factores de Tiempo , Listas de EsperaRESUMEN
Introduction: SARS-CoV-2 is a RNA virus that associates with heterogeneous clinical manifestations and complications. Auto-antibodies are identified in approximately 50% of hospitalized COVID-19 patients. Objectives: To determine the global incidence of myositis-related auto-antibodies (non Jo1-RNA synthetases: anti-PL7, anti-PL12, anti-EJ, anti-OJ and RNA-sensor: anti-MDA5) in our laboratory during COVID-19 pandemics, and to describe the clinical and laboratory features of these patients. Study design: A retrospective study was performed from 2015 to 2021 in a cohort of 444 patients with suspected inflammatory myopathy. The incidence of positive results for the MSA was expressed as absolute value per year for the reference population. Immunoblot analysis, indirect immunofluorescence and HLA typing of 36 patients with positivity for MSAs were collected and analyzed. Results: We observed MSA positive in 28 patients in 2020 and 36 patients in 2021, representing a mean increase of 6-fold respect to previous years since 2015 (range, 0 to 19). In 2020, the most common antibody detected was anti-MDA5 (68%). In contrast, in 2021 the most common antibodies were anti-PL7 and/or anti-PL12 (69%). All patients in 2021 with positive anti-synthetases were fully vaccinated, 4 had previous documented infection, with median time from vaccine to MSA positivity of 5 months. Eight out of 36 patients (22%) reported clinical onset after SARS-CoV-2 vaccination and 6 out of 36 (17%) presented clinical and/or radiological worsening after SARS-CoV-2 vaccination. All patients presented with a known human leukocyte antigen (HLA)-DRB1* allele associated with ASS. The most prevalent alleles identified were DRB1*03:01, DRB1*04, DRB1*11:01, corresponding to 70% (16/23) of our cohort. Conclusions: Our preliminary data show an increased incidence of anti-synthetase antibodies during COVID-19 pandemic and SARS-CoV-2 vaccination associated to HLA DRB1* risk allele. Differential profiles of MSA specificities were observed: mainly against RNA-sensors in 2020 and against RNA-synthetases in 2021. Further studies are needed to support the association between SARS-CoV-2 infection and/or vaccination and the occurrence of this autoimmune syndrome.
RESUMEN
OBJECTIVE: The aim of this study was to describe the incidence rate (IR) of adverse drug reactions (ADRs) in daily clinical practice, related to disease-modifying antirheumatic drugs (DMARDs) and biologic agents (BA) in rheumatoid arthritis (RA) patients, and to analyze factors causing discontinuation due to ADRs. METHODS: This was a prospective observational study (October 2010 to October 2011). RA patients who were attended in our hospital taking DMARDs or BA during the study period were included. ADRs were injuries related to these drugs and registered with a software system in routine visits. ADRs could be mild (lowering dosage), moderate (drug discontinuation), or severe (hospital admission). The IR of ADR per 100 patient-years was estimated using survival techniques. Cox regression models (HR; 95% confidence interval) were used to explore factors associated with discontinuation due to ADRs. RESULTS: In total, 1202 patients were analyzed, with 158 ADRs (IR = 15.2). Of all ADRs, 80.4% required drug discontinuation (IR = 12.2). Age, less disease and therapy duration, taking corticoids, and combined therapy versus monotherapy (HR = 3; 95% CI: 2.0-4.4) were the factors independently associated to discontinuation due to ADRs. We did not find statistical differences between the different monotherapy regimens. Regarding combinations, Methotrexate + BA had the lowest risk of discontinuation compared to the rest (HR = 0.24; 95% CI: 0.09-0.6). CONCLUSIONS: We have estimated the incidence of ADRs related to DMARDs/BA in real-life conditions. We confirm the role of combined therapy in the development of discontinuations due to ADRs, except for BA + MTX, which did not show an increase of toxicity compared to monotherapy. This combination seems to be safer than others.
Asunto(s)
Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Productos Biológicos/efectos adversos , Adulto , Anciano , Antirreumáticos/uso terapéutico , Productos Biológicos/uso terapéutico , Bases de Datos Factuales , Quimioterapia Combinada , Femenino , Humanos , Masculino , Metotrexato/efectos adversos , Metotrexato/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoAsunto(s)
Carbonato de Calcio , Minería , Cuarzo , Silicosis/etiología , Adulto , Edad de Inicio , Materiales de Construcción , Cristalización , Adhesión a Directriz , Humanos , Trasplante de Pulmón , Masculino , Exposición Profesional , Salud Laboral/legislación & jurisprudencia , Salud Laboral/normas , Tamaño de la Partícula , Dióxido de Silicio , Silicosis/mortalidad , Indemnización para Trabajadores/legislación & jurisprudenciaRESUMEN
OBJECTIVE: To evaluate whether an early cognitive-behavioral treatment complementary to a rheumatologic care program, for patients with recent-onset temporary work disability caused by musculoskeletal disorders (MSDs) is effective. METHODS: Patients with an MSD-related temporary work disability episode from 3-8 weeks' duration who were in a rheumatologic care program were randomized into a control group (rheumatologic care program) or an intervention group (rheumatologic care program plus cognitive-behavioral treatment). Enrollment lasted 24 months and followup lasted 6-24 months. Efficacy variables included duration of temporary work disability episodes, total number of work days saved, relative efficacy, and relative rate to return to work. An economic evaluation was also performed. RESULTS: One hundred eighty-one patients were included (66 control and 115 intervention patients), generating 222 episodes of MSD-related temporary work disability. Episodes tended to be shorter in the intervention group than in the control group (mean 98 versus 127 days; P = 0.053), with a relative efficacy of 22.9%. There were no differences in duration of the first episode between groups (mean 105 versus 110 days; P = 0.79), but relapse episodes were significantly shorter in the intervention group (mean 63 days versus 197 days; P = 0.0002). Costs were also lower in the intervention group. To save 1 day of temporary work disability, $13.50 had to be invested in the program. Each dollar invested generated a benefit of $4.08. The program had a net benefit of $172,607. CONCLUSION: Early cognitive-behavioral treatment complementary to a rheumatologic care program is cost-effective, adds >20% efficacy to the rheumatologic care program, and reduces the duration of relapses.
Asunto(s)
Terapia Cognitivo-Conductual/métodos , Empleos en Salud , Enfermedades Musculoesqueléticas/terapia , Adulto , Terapia Cognitivo-Conductual/economía , Análisis Costo-Beneficio , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Musculoesqueléticas/psicología , Recurrencia , Resultado del Tratamiento , Lugar de TrabajoRESUMEN
OBJECTIVE: To analyze changes in the lag time to first disease modifying antirheumatic drug (DMARD) prescription since onset of symptoms of rheumatoid arthritis (RA) over the last 2 decades in Spain. PATIENTS AND METHOD: Review of medical records of 865 patients diagnosed with RA living in Spain and attended in specialty care settings of the National Health System. The principal variable was the lag time between the onset of symptoms of RA and the date of first DMARD therapy prescription. Analyses were performed by year and five-year periods and differences between groups were assessed by χ(2) test, Student t test and analysis of variance. RESULTS: Sociodemographic and clinical characteristics corresponded to a typical cross-sectional population of patients diagnosed with RA. The median lag time between symptom onset and first DMARD therapy was 14 months (6-36) for the whole group. However, a significant shortening of time to first DMARD was observed over the last two decades (-4.59±0.2 months by year; P<001). Shortening of time to first DMARD was mainly due to a shortening of time to first visit with specialists since onset of symptoms with a smaller decrease in time from first visit to first prescription of a DMARD agent. CONCLUSIONS: A significant shortening in the lag time to first DMARD therapy was observed over the last 2 decades in Spain, being a significant reduction in the time to first visit with a specialists its major cause.
RESUMEN
OBJECTIVE: To analyze sociodemographic and clinic-associated factors of patients with rheumatoid arthritis (RA) undergoing any orthopedic surgery (AOS) and total joint replacement (TJR) in Spain. METHODS: A retrospective medical record review was performed in a probabilistic sample of 1379 RA patients from 46 centers distributed in 16 of 19 regions in Spain. Sociodemographic and clinical features, use of drugs, and arthritis-related joint surgeries were recorded following a standardized protocol. Gross domestic product (GDP) data were obtained from the National Statistical Index. RESULTS: Of 1379 patients, a total of 358 (26%) underwent one or more joint surgeries, and 194 (14%) had a TJR. The median time to first orthopedic procedure was 12.5 years from presentation of RA and the estimated rate was 5.6 surgeries per 100 person-years. The rate of AOS was increased in women, patients with RA with extraarticular complications, with longterm RA (> 10 yrs), with functional grade III-IV, and with persistent inflammatory disease. The risk factors for undergoing a TJR were longterm RA, functional grade III-IV, and extraarticular complications. Patients from regions with higher GDP per capita were more likely to undergo a procedure. CONCLUSION: Clinical variables reflecting disease activity and severity are predictors of orthopedic surgery, but geographic and socioeconomic variables were also independently associated with the rate of orthopedic surgery.