Long-term efficacy and safety of subcutaneous tocilizumab in clinical trials of polyarticular or systemic juvenile idiopathic arthritis.

OBJECTIVE: To investigate the safety and efficacy of subcutaneous tocilizumab (SC-TCZ) treatment in a long-term extension (LTE) of clinical trials in polyarticular or systemic juvenile idiopathic arthritis (pJIA, sJIA). METHODS: Patients with pJIA or sJIA from two open-label, 52-week phase 1 b core trials of SC-TCZ who had adequate response per investigator assessment entered the LTE and continued SC-TCZ treatment according to body weight-based dosing regimens until commercial availability or up to 5 years. Pharmacokinetics, pharmacodynamics, and efficacy were assessed for up to 3 years and safety for up to 5 years in the LTE. RESULTS: Forty-four patients with pJIA and 38 patients with sJIA entered the LTE. Tocilizumab trough concentrations were maintained within the range expected to provide clinical benefit (mean values: pJIA, ∼10 µg/ml; sJIA, ∼75 µg/ml over 3 years). Pharmacodynamic parameters (interleukin-6, soluble interleukin-6 receptor, erythrocyte sedimentation rate, C-reactive protein) were maintained throughout the LTE at levels achieved in the core trials. Inactive disease per American College of Rheumatology provisional criteria was reported for 90% (17/19) and 53% (8/15) of patients with pJIA and 91% (10/11) and 92% (12/13) of patients with sJIA in the <30 kg and ≥30 kg body weight groups, respectively. Serious adverse events in the LTE were reported in six patients with pJIA (13.6%; five serious infections) and five patients with sJIA (13.2%; one serious infection). CONCLUSION: Patients with pJIA or sJIA experienced long-term disease control with SC-TCZ treatment. Long-term safety was consistent with the known tocilizumab safety profile.

Las habilidades de comunicación de los aspirantes a la certificación en Reumatología se asocian con su desempeño en el examen clínico objetivo estructurado / Communication skills in candidates for accreditation in rheumatology are correlated with candidate's performance in the objective structured clinical examination

Introducción: El Consejo Mexicano de Reumatología certifica anualmente reumatólogos mediante una prueba teórica y un examen clínico objetivo estructurado (ECOE). Desde el año 2015, se evalúan las habilidades de comunicación (HC) de los candidatos. Los objetivos fueron comparar las HC evaluadas por el paciente (HCP) y por el médico (HCM) y correlacionarlas con el desempeño de los candidatos en el ECOE. Material y métodos: Durante los años 2015, 2016 y 2017, se evaluaron las HC en las estaciones dinámicas, mediante una escala de Likert aplicada a 8 áreas. Pacientes y evaluadores fueron entrenados cada año para calificar a los aspirantes, lo cual se realizó el día del ECOE, de manera ciega, por ambos. Se calcularon coeficientes de correlación de Pearson. Resultados: En general, a lo largo de los 3años, los candidatos obtuvieron puntajes altos en las HC. Los pacientes puntuaron mejor a los candidatos que los evaluadores médicos. Las HCP y las HCM correlacionaron entre sí (de leve a moderado) en la mayoría de las estaciones. El puntaje de las HC de cada candidato correlacionó con su desempeño en la estación correspondiente; se encontraron mejores correlaciones con las HCP. El promedio de las HC de cada candidato correlacionó con el desempeño global en el ECOE, pero no así con la prueba teórica (salvo en el año 2017, cuando hubo una correlación baja). Conclusiones: Las HC evaluadas durante un examen de certificación en Reumatología correlacionan con el desempeño de cada candidato en cada estación y en el ECOE global

Background: The Mexican Accreditation Council for Rheumatology annually certifies trainees in Rheumatology using a multiple-choice test and an objective structured clinical examination (OSCE). Since 2015, candidate's communication skills (CS) have been rated by both patients and by physician examiners and correlated with results on the OSCE. This study compared the CS from candidates to annual accreditation in Rheumatology as rated by patients and by physician examiners, and assessed whether these correlated with candidate's performance in the OSCE. Material and methods: From 2015 to 2017, 8areas of CS were evaluated using a Likert scale, in each OSCE station that involved a patient. Both patient and physician evaluators were trained annually and their evaluations were performed blindly. The associations were calculated using the Pearson correlation coefficient. Results: In general, candidates were given high CS scores; the scores from patients of the candidate's CS were better than those of physician examiners; within the majority of the stations, both scores were found to correlate moderately. In addition, the scoring of CS correlated with trainee performance at the corresponding OSCE station. Interestingly, better correlations were found when the skills were rated by the patients compared to physician scores. The average CS score was correlated with the overall OSCE performance for each trainee, but not with the multiple-choice test, except in the 2017 accreditation process, when a weak correlation was found. Conclusions: CS assessed during a national accreditation process correlated with the candidate's performance at the station level and with the overall OSCE

Communication skills in candidates for accreditation in rheumatology are correlated with candidate's performance in the objective structured clinical examination. / Las habilidades de comunicación de los aspirantes a la certificación en Reumatología se asocian con su desempeño en el examen clínico objetivo estructurado.

BACKGROUND: The Mexican Accreditation Council for Rheumatology annually certifies trainees in Rheumatology using a multiple-choice test and an objective structured clinical examination (OSCE). Since 2015, candidate's communication skills (CS) have been rated by both patients and by physician examiners and correlated with results on the OSCE. This study compared the CS from candidates to annual accreditation in Rheumatology as rated by patients and by physician examiners, and assessed whether these correlated with candidate's performance in the OSCE. MATERIAL AND METHODS: From 2015 to 2017, 8areas of CS were evaluated using a Likert scale, in each OSCE station that involved a patient. Both patient and physician evaluators were trained annually and their evaluations were performed blindly. The associations were calculated using the Pearson correlation coefficient. RESULTS: In general, candidates were given high CS scores; the scores from patients of the candidate's CS were better than those of physician examiners; within the majority of the stations, both scores were found to correlate moderately. In addition, the scoring of CS correlated with trainee performance at the corresponding OSCE station. Interestingly, better correlations were found when the skills were rated by the patients compared to physician scores. The average CS score was correlated with the overall OSCE performance for each trainee, but not with the multiple-choice test, except in the 2017 accreditation process, when a weak correlation was found. CONCLUSIONS: CS assessed during a national accreditation process correlated with the candidate's performance at the station level and with the overall OSCE.

The method used to set the pass mark in an objective structured clinical examination defines the performance of candidates for certification as rheumatologists. / El método para establecer el punto de corte en el examen clínico objetivo estructurado define el desempeño de los candidatos a la certificación como reumatólogo.

BACKGROUND: The Mexican Accreditation Council for Rheumatology certifies trainees (TR) on an annual basis using both a multiple-choice question (MCQ) test and an objective structured clinical examination (OSCE). For 2013 and 2014, the OSCE pass mark (PM) was set by criterion referencing as ≥6 (CPM), whereas overall rating of borderline performance method (BPM) was added for 2015 and 2016 accreditations. We compared OSCE TR performance according to CPM and BPM, and examined whether correlations between MCQ and OSCE were affected by PM. METHODS: Forty-three (2015) and 37 (2016) candidates underwent both tests. Altogether, OSCE were integrated by 15 validated stations; one evaluator per station scored TR performance according to a station-tailored check-list and a Likert scale (fail, borderline, above range) of overall performance. A composite OSCE score was derived for each candidate. Appropriate statistics were used. RESULTS: Mean (±standard derivation [SD]) MCQ test scores were 6.6±0.6 (2015) and 6.4±0.6 (2016) with 5 candidates receiving a failing score each year. Mean (±SD) OSCE scores were 7.4±0.6 (2015) and 7.3±0.6 (2016); no candidate received a failing CPM score in either 2015 or 2016 OSCE, although 21 (49%) and 19 (51%) TR, respectively, received a failing BPM score (calculated as 7.3 and 7.4, respectively). Stations for BPM ranged from 4.5 to 9.5; overall, candidates showed better performance in CPM. In all, MCQ correlated with composite OSCE, r=0.67 (2015) and r=0.53 (2016); P≤.001. Trainees with a passing BPM score in OSCE had higher MCQ scores than those with a failing score. CONCLUSIONS: Overall, OSCE-PM selection impacted candidates' performance but had a limited affect on correlation between clinical and practical examinations.

Enfermedad de Kawasaki en un hospital pediátrico en México / Kawasaki disease at a pediatric hospital in Mexico

Resumen: Introducción: La enfermedad de Kawasaki (EK) es una de las vasculitis sistémicas más comunes en niños menores de 5 años de edad. La epidemiología de la enfermedad no está bien establecida en México. El objetivo de este trabajo fue describir la epidemiología, características clínicas y tratamiento de los pacientes con EK atendidos en el Hospital Infantil de México Federico Gómez (HIMFG). Métodos: Se realizó un estudio retrospectivo, descriptivo y analítico de pacientes diagnosticados con EK en el HIMFG en el periodo comprendido entre enero de 2004 y diciembre de 2014. Resultados: Se analizaron 204 casos, la mayoría de sexo masculino (55%), con mediana de edad de 32.5 meses (6-120) y una tasa de hospitalización del 96%. El 20% de los pacientes presentó EK incompleto. No se reportaron diferencias en la somatometría ni signos vitales. La sintomatología más frecuente fue fiebre, conjuntivitis (89%), cambios orales (84%), faringitis (88%) y lengua en fresa (83%). Se encontraron reactantes de fase aguda más elevados en las presentaciones clásicas. Se reportaron alteraciones ecocardiográficas en 60 pacientes (29%), de las cuales el 12% fueron ectasia y el 11% aneurismas coronarios. Por otro lado, 169 pacientes (83%) recibieron inmunoglobulina intravenosa (IGIV), 18 (9%) resistencia a IGIV, 6 (3%) requirieron corticosteroides y 2 (1%) infliximab; todos recibieron ácido acetilsalicílico. Conclusiones: No se encontraron diferencias importantes entre las presentaciones clásicas e incompletas. La incidencia de alteraciones cardiacas es menor a la reportada previamente en México, pero similar a la de otros países.

Abstract: Background: Kawasaki disease (KD) is one of the most common systemic vasculitis in children under 5 years of age. The epidemiology of the disease is not well established in Mexico. The objective of this study was to describe the epidemiology, clinical features and treatment of patients with KD at the Hospital Infantil de Mexico Federico Gomez (HIMFG). Methods: We conducted a retrospective, descriptive and analytical study of patients diagnosed from January 2004 to December 2014 with KD in the HIMFG. Results: We analyzed 204 cases from which 55% were male, with a median age of 32.5 months (6-120) and a rate of hospitalization of 96%. Twenty percent of patients presented incomplete KD. No differences in the somatometric measurements or vitals were reported. The most frequent symptoms were fever, conjunctivitis (89%), oral changes (84%), pharyngitis (88%) and strawberry tongue (83%). We found higher acute phase reactants in the classic presentation. Echocardiographic alterations in 60 patients (29%), of which 12% were ectasia and 11% reported coronary aneurysms. On the other hand, 169 (83%) patients received intravenous immunoglobulin (IVIG), 18 (9%) presented resistance to IVIG, 6 (3%) required corticosteroids, and 2 (1%) infliximab; all received acetylsalicylic acid. Conclusions: There were no important differences between classic and incomplete presentations. The incidence of cardiac alterations is less than previously reported in Mexico, but similar to that of other countries.

[Kawasaki disease at a pediatric hospital in Mexico]. / Enfermedad de Kawasaki en un hospital pediátrico en México.

BACKGROUND: Kawasaki disease (KD) is one of the most common systemic vasculitis in children under 5 years of age. The epidemiology of the disease is not well established in Mexico. The objective of this study was to describe the epidemiology, clinical features and treatment of patients with KD at the Hospital Infantil de Mexico Federico Gomez (HIMFG). METHODS: We conducted a retrospective, descriptive and analytical study of patients diagnosed from January 2004 to December 2014 with KD in the HIMFG. RESULTS: We analyzed 204 cases from which 55% were male, with a median age of 32.5 months (6-120) and a rate of hospitalization of 96%. Twenty percent of patients presented incomplete KD. No differences in the somatometric measurements or vitals were reported. The most frequent symptoms were fever, conjunctivitis (89%), oral changes (84%), pharyngitis (88%) and strawberry tongue (83%). We found higher acute phase reactants in the classic presentation. Echocardiographic alterations in 60 patients (29%), of which 12% were ectasia and 11% reported coronary aneurysms. On the other hand, 169 (83%) patients received intravenous immunoglobulin (IVIG), 18 (9%) presented resistance to IVIG, 6 (3%) required corticosteroids, and 2 (1%) infliximab; all received acetylsalicylic acid. CONCLUSIONS: There were no important differences between classic and incomplete presentations. The incidence of cardiac alterations is less than previously reported in Mexico, but similar to that of other countries.

Desempeño del examen clínico objetivo estructurado como instrumento de evaluación en la certificación nacional como reumatólogo / Performance of an objective structured clinical examination in a national certification process of trainees in rheumatology

Objetivo. Determinar la validez de constructo y la confiabilidad de un examen clínico objetivo estructurado (ECOE) en la evaluación de una certificación nacional como reumatólogo. Método. En 2013 y 2014, se aplicaron sendos ECOE y evaluación teórica (ET) a 32 y 38 residentes aspirantes a la certificación de reumatólogo, respectivamente. Se incluyeron 12 y 15 estaciones calificadas mediante lista de cotejo validada. Previamente, 3 reumatólogos certificados realizaron sendas pruebas piloto. Se calculó la puntuación global del ECOE y se evaluó su desempeño. Resultados. En 2013, la media ± DE del ECOE fue de 7,1 ± 0,6) y ningún aspirante tuvo calificación reprobatoria (CR); la media de la ET fue de 6,5 ± 0,6 y 7 aspirantes (21,9%) tuvieron CR (< 6). En 2014, la media del ECOE fue de 6,7 ± 0,6) y 3 aspirantes (7,9%) tuvieron CR, de los cuales 2 reprobaron la ET; la media de la ET fue de 6,4 ± 0,5) y 7 aspirantes (18,5%) tuvieron CR, 2 de los cuales reprobaron el ECOE. En 2013, la correlación entre el ECOE y la ET fue de r = 0,44, p = 0,006. En ambos años, los reumatólogos certificados obtuvieron mejores calificaciones en el ECOE que los residentes. El porcentaje de aprobados en la ET fue mayor entre quienes aprobaron el ECOE que entre quienes lo reprobaron: 86% vs. 67%, p = 0,02. Se aplicaron 9 estaciones en ambos años y sus puntuaciones mostraron correlación de 0,81 a 0,95, p ≤ 0,01. Conclusión. El ECOE es una herramienta adecuada para evaluar las competencias clínicas de los aspirantes a la certificación (AU)

Objective. To assess reliability and validity of the objectively-structured clinical examination (OSCE) applied in postgraduate certification processes by the Mexican Board of Rheumatology. Method. Thirty-two (2013) and 38 (2014) Rheumatology trainees (RTs) underwent an OSCE consisting of 12 and 15 stations respectively, scored according to a validated check-list, as well as 300-multiple-choice 300 question examination (MCQ). Previously, 3 certified rheumatologists underwent a pilot-OSCE. A composite OSCE score was obtained for each participant and its performance examined. Results. In 2013, OSCE mean score was 7.1 ± 0.6 with none RT receiving a failing score while the MCQ score was 6.5 ± 0.6 and 7 (21.9%) RTs receiving a failing (< 6) score. In 2014, the OSCE score was 6.7 ± 0.6, with 3 (7.9%) RTs receiving a failing score (2 of them also failed MCQ) while the MCQ score was 6.4 ± 0.5 and 7 (18.5%) RTs were disqualified (2 of them also failed OSCE). A significant correlation between the MCQ and the OSCE scores was observed in the 2013 (r=0.44; P=0.006). Certified rheumatologists performed better than RTs at both OSCE. Overall, 86% of RTs obtaining an OSCE passing score also obtained a MCQ passing score, while this was only 67% (P=.02) among those who obtained an OSCE failing score. Nine stations were applied at both consecutive years. Their performance was similar in both certification processes, with correlation coefficients ranging from 0.81 to 0.95 (P≤0.01). Conclusion. The OSCE is a valid and reliable tool to assess the Rheumatology clinical skills in RTs (AU)

Performance of an objective structured clinical examination in a national certification process of trainees in rheumatology.

OBJECTIVE: To assess reliability and validity of the objectively-structured clinical examination (OSCE) applied in postgraduate certification processes by the Mexican Board of Rheumatology. METHOD: Thirty-two (2013) and 38 (2014) Rheumatology trainees (RTs) underwent an OSCE consisting of 12 and 15 stations respectively, scored according to a validated check-list, as well as 300-multiple-choice 300 question examination (MCQ). Previously, 3 certified rheumatologists underwent a pilot-OSCE. A composite OSCE score was obtained for each participant and its performance examined. RESULTS: In 2013, OSCE mean score was 7.1±0.6 with none RT receiving a failing score while the MCQ score was 6.5±0.6 and 7 (21.9%) RTs receiving a failing (< 6) score. In 2014, the OSCE score was 6.7±0.6, with 3 (7.9%) RTs receiving a failing score (2 of them also failed MCQ) while the MCQ score was 6.4±0.5 and 7 (18.5%) RTs were disqualified (2 of them also failed OSCE). A significant correlation between the MCQ and the OSCE scores was observed in the 2013 (r=0.44; P=0.006). Certified rheumatologists performed better than RTs at both OSCE. Overall, 86% of RTs obtaining an OSCE passing score also obtained a MCQ passing score, while this was only 67% (P=.02) among those who obtained an OSCE failing score. Nine stations were applied at both consecutive years. Their performance was similar in both certification processes, with correlation coefficients ranging from 0.81 to 0.95 (P≤0.01). CONCLUSION: The OSCE is a valid and reliable tool to assess the Rheumatology clinical skills in RTs.

Arteritis de Takayasu tipo III en un paciente pediátrico. Reporte de caso y revisión de la literatura / Type III Takayasu's arteritis in a pediatric patient. Case report and review of the literature

La arteritis de Takayasu (AT) o «enfermedad sin pulsos» es la tercera vasculitis más frecuente en la infancia. Es crónica, idiopática, granulomatosa y afecta a vasos grandes. Afecta a las mujeres, con una relación 4:1; con una edad promedio de 26 años. Su causa es desconocida. Presentamos el caso de una niña de 7 años y 7 meses de edad, con AT tipo III de la clasificación de Numano, en fase isquémica, a la que se le inició tratamiento con glucocorticoides e inmunosupresores, así como angioplastia temprana, por la severidad del cuadro clínico. Tuvo una evolución satisfactoria. El diagnóstico de AT antes de los 10 años se realiza en el 2% de los pacientes; el retraso en el diagnóstico es en promedio de 19 meses; el curso de la enfermedad es variable a pesar del tratamiento inmunosupresor y quirúrgico (AU)

Takayasu's arteritis (TA), also known as "pulseless disease", is the third most common vasculitis in childhood. It is a chronic, idiopathic, granulomatous vasculitis that involves large vessels. It occurs most commonly in females with a 4:1 ratio over males; the average age of appearance is 26 years. Its cause is unknown. Here we report the case of a 7 year old girl, with type III TA according to the Numano classification, in the ischemic phase, treated with corticosteroids and immunosuppressive agents and early angioplasty due to the severity of the disease. The outcome was satisfactory. The diagnosis of TA in children under 10 years of age is made only in 2% of them. The delay in diagnosis reaches a mean of 19 months. The course of the disease is variable despite surgical and immunosuppressive treatment (AU)

Type III Takayasu's arteritis in a pediatric patient. Case report and review of the literature.

Takayasu's arteritis (TA), also known as "pulseless disease", is the third most common vasculitis in childhood. It is a chronic, idiopathic, granulomatous vasculitis that involves large vessels. It occurs most commonly in females with a 4:1 ratio over males; the average age of appearance is 26 years. Its cause is unknown. Here we report the case of a 7-year-old girl, with type III TA according to the Numano classification, in the ischemic phase, treated with corticosteroids and immunosuppressive agents and early angioplasty due to the severity of the disease. The outcome was satisfactory. The diagnosis of TA in children under 10 years of age is made only in 2% of them. The delay in diagnosis reaches a mean of 19 months. The course of the disease is variable despite surgical and immunosuppressive treatment.

Enfermedad de Kawasaki en fase de convalecencia con afección cardiaca: trombo intra-sacular en aneurisma gigante de ambas coronarias. A propósito de un caso / Kawasaki’s disease in remission with cardiac involvement: Intrasacular thrombus in a Giant Aneurism of both coronary arteries. Case report

La enfermedad de Kawasaki es de relevancia en la práctica pediátrica debido a que es la vasculitis sistémica de origen desconocido más común y la primera causa de cardiopatía adquirida en pacientes jóvenes. Su complicación principal es cardiaca, ya que el 25% de los pacientes sufre la formación de aneurismas coronarios si no reciben de manera oportuna tratamiento médico. Reportamos el caso de un niño de 4 meses de edad, con enfermedad de Kawasaki, que recibe tratamiento con gammaglobulina y ácido acetilsalicílico. El ecocardiograma inicial no presenta ectasias o aneurismas. Ingresa en nuestro hospital con datos de choque cardiogénico, se documenta por ecocardiografía aneurismas coronarios, con trombo intra-sacular e infarto agudo al miocardio. Recibe terapia fibrinolítica, con respuesta adecuada: disminución del tamaño de los aneurismas y del trombo intra-sacular. Actualmente el paciente se encuentra asintomático y en vigilancia en la consulta externa, recibe tratamiento con warfarina y ácido acetilsalicílico. El diagnóstico y el tratamiento oportuno, así como la identificación de factores de riesgo, pueden evitar complicaciones fatales a nivel cardiovascular. El tratamiento en los primeros 10 días de la enfermedad con gammaglobulina y ácido acetilsalicílico reduce del 4,7 al 25% de las complicaciones cardiacas (AU)

Kawasaki disease is of relevance in pediatric practice because it is a systemic vasculitis of unknown origin and the most common cause of acquired heart disease in young patients. Its main complication is the formation of a coronary aneurysm in 25% of patients, unless they receive timely medical treatment. We report the case of a 4 month old male child with Kawasaki’s disease, received treatment with gammaglobulin and acetyl-salicylic acid, in which the initial echocardiogram showed aneurysms. Admitted to our hospital with cardiogenic shock, we documented by echocardiography the presence of coronary aneurysms with intra-saccular thrombus and acute myocardial infarction. He received fibrinolytic therapy, with an adequate response: the size of aneurysms decreased, as did the intra-saccular thrombus. Currently the patient is asymptomatic and receiving treatment with warfarin and acetylsalicylic acid. The diagnosis and treatment, as well as identification of risk factors can prevent fatal complications at the cardiovascular level. The treatment in the first 10 days of illness with gammaglobulin and acetylsalicylic acid reduced cardiac complications from 4.7 to 25% (AU)

[Kawasaki's disease in remission with cardiac involvement: intrasacular thrombus in a giant aneurism of both coronary arteries. Case report]. / Enfermedad de Kawasaki en fase de convalecencia con afección cardiaca: trombo intra-sacular en aneurisma gigante de ambas coronarias. A propósito de un caso.

Kawasaki disease is of relevance in pediatric practice because it is a systemic vasculitis of unknown origin and the most common cause of acquired heart disease in young patients. Its main complication is the formation of a coronary aneurysm in 25% of patients, unless they receive timely medical treatment. We report the case of a 4 month old male child with Kawasaki's disease, received treatment with gammaglobulin and acetyl-salicylic acid, in which the initial echocardiogram showed aneurysms. Admitted to our hospital with cardiogenic shock, we documented by echocardiography the presence of coronary aneurysms with intra-saccular thrombus and acute myocardial infarction. He received fibrinolytic therapy, with an adequate response: the size of aneurysms decreased, as did the intra-saccular thrombus. Currently the patient is asymptomatic and receiving treatment with warfarin and acetylsalicylic acid. The diagnosis and treatment, as well as identification of risk factors can prevent fatal complications at the cardiovascular level. The treatment in the first 10 days of illness with gammaglobulin and acetyl-salicylic acid reduced cardiac complications from 4.7 to 25%.