Prospective, historically controlled study to evaluate the efficacy and safety of a new paediatric formulation of nifurtimox in children aged 0 to 17 years with chagas disease one year after treatment (Chico)

Nifurtimox is a recommended treatment for Chagas disease, but data from treated children are limited. We investigated the efficacy, safety and tolerability of nifurtimox administered as divisible, dispersible 30 mg and 120 mg tablets in children with Chagas disease. In this blinded, controlled study conducted January 2016–July 2018, 330 patients aged <18 years from 25 medical centres across three South American countries were randomised 2:1 to nifurtimox 10–20 mg/kg/day (aged <12 years) or 8–10 mg/kg/day (aged ≥12 years) for 60 days (n = 219), or for 30 days plus placebo for 30 days (n = 111) (ClinicalTrials.gov NCT02625974). The primary outcome was anti-Trypanosoma cruzi serological response (negative seroconversion or seroreduction ≥20% in mean optical density from baseline determined by two conventional enzyme-linked immunosorbent assays) at 12 months in the 60-day treatment group versus historical placebo controls. Nifurtimox for 60 days achieved negative seroconversion (n = 10) and seroreduction (n = 62) in 72 patients (serological response 32.9%; 95% confidence interval [CI] 26.4%, 39.3%, of all treated patients), confirming superiority relative to the upper 95% CI of 16% for controls. In patients aged <8 months, 10/12 treated for 60 days (83.3%) and 5/7 treated for 30 days (71.4%) achieved negative seroconversion. Overall serological response was lower for 30-day than for 60-day nifurtimox (between-treatment difference 14.0% [95% CI 3.7%, 24.2%]). The frequency of T. cruzi-positive quantitative polymerase chain reactions decreased substantially from baseline levels (60-day regimen 53.4% versus 1.4%; 30-day regimen 51.4% versus 4.5%). Study drug-related treatment-emergent adverse events (TEAEs), which were observed in 62 patients (28.3%) treated for 60 days and 29 patients (26.1%) treated for 30 days, were generally mild or moderate and resolved without sequelae; 4.2% of all TEAEs led to nifurti-mox discontinuation. Age-and weight-adjusted nifurtimox for 60 days achieved a serological response at 12 months post-treatment that was superior to historical placebo, was well tolerated and had a favourable safety profile in children with Chagas disease. Although, at 1 year serological follow-up, efficacy of the shorter nifurtimox treatment was not comparable to the 60-day treatment regimen for the overall study population, further long-term follow-up of the patients will provide important information about the progress of serological conversion in children treated with nifurtimox, as well as the potential efficacy difference between the two regimens over time.Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Castro, Luis. Centro de Atención E Investigación Médica; ColombiaFil: Dib, Juan C.. Universidad del Norte; ColombiaFil: Grossmann, Ulrike. No especifíca;Fil: Huang, Erya. No especifíca;Fil: Moscatelli, Guillermo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Pinto Rocha, Jimy José. Fundación Ceades; BoliviaFil: Ramírez, Teresa Estela. Centro de Enfermedad de Chagas y Patologias Regionales; Argentin

Perspectivas de la empresa y la economía mexicana frente a la reestructuración productiva

1 archivo PDF (404 páginas)Este texto se presenta una reflexión de investigadores de la UAM, así como de otras Instituciones de Educación Superior respecto al marco en el que se han desenvuelto las empresas mexicanas en los últimos años, así como del desarrollo en algunos de sus sistemas organizacionales. PALABRAS CLAVE: Mexico Economic policy 1970-1994

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

Pasados y presente. Estudios para el profesor Ricardo García Cárcel

Ricardo García Cárcel (Requena, 1948) estudió Historia en Valencia bajo el magisterio de Joan Reglà, con quien formó parte del primer profesorado de historia moderna en la Universidad Autónoma de Barcelona. En esta universidad, desde hace prácticamente cincuenta años, ha desarrollado una extraordinaria labor docente y de investigación marcada por un sagaz instinto histórico, que le ha convertido en pionero de casi todo lo que ha estudiado: las Germanías, la historia de la Cataluña moderna, la Inquisición, las culturas del Siglo de Oro, la Leyenda Negra, Felipe II, Felipe V, Austrias y Borbones, la guerra de la Independencia, la historia cultural, los mitos de la historia de España... Muy pocos tienen su capacidad para reflexionar, ordenar, analizar, conceptualizar y proponer una visión amplia y llena de matices sobre el pasado y las interpretaciones historiográficas. A su laboriosidad inimitable se añade una dedicación sin límites en el asesoramiento de alumnos e investigadores e impulsando revistas, dosieres, seminarios o publicaciones colectivas. Una mínima correspondencia a su generosidad lo constituye este volumen a manera de ineludible agradecimiento

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

Influencia de la estrategia .didáctica "MORE SPEAKING" en el desarrollo de la habilidad oral del idioma inglés en estudiantes del sexto grado "B" nivel primaria de la l.E. 0620 - Aplicación del distrito de Tarapoto - 2011

The didactic strategy MORE SPEAKING arises as an altemative because of the absence of motivating strategies from teachers, where it is observed that the motivation is untied of the learning activities; according to that this strategy allows the development of the speaking skill of the English language through the connection of the motivation with the learning activities, achieving this way a significant learning. The problem, hypothesis and general objective have been structured by means of the relationship between the variables strategy MORE SPEAKING and the development of the speaking skill of the English language. The theoretical body of the didactic strategy MORE SPEAKING was systematized endowing it with a purpose, didactic processes and a theoretical support based on the philosophical, psychological and pedagogic foundation. The studied population was formed by 88 students and the sample by 25 students who were evaluated by means of a pre and post-test to determine the significant influence or not of the didactic strategy MORE SPEAKING in the development of the speaking skill of the English language. To measure the students of the six grade B didactic strategy, a pre-test was applied at the beginning and a post test at the end of the six strategy pedagogic workshops; the tests were made up of 30 items divided into four components. The investigation design was pre-experimental with a pre and post-test; with an experimental group, those groups were intact not equivalent. According to the statistical results in the chart Nº01 where a great progress is demonstrated between the Pre-test and the Post-test. For this reason in the results of the hypothesis test according to the chart Nº 6 reject the null hypothesis and the investigation hypothesis is accepted. That is to say that the application of the didactic strategy MORE SPEAKING incremented significantly the development of the speaking skill of the English language in the students of the six grade B primary level of the Educational lnstitution Nº 0620-Aplication of Tarapoto district.La estrategia didáctica "MORE SPEAKING" surge como una alternativa ante la ausencia de estrategias motivacionales por parte de los docentes, las mismas que están desligadas de las actividades de aprendizaje; en tal sentido esta estrategia permite el desarrollo de la habilidad oral del idioma inglés a través de la conexión de la motivación con las actividades de aprendizaje, logrando así un aprendizaje significativo. El problema, hipótesis y objetivo general se han estructurado mediante la relación de las variables; estrategia "MORE SPEAKING" y el desarrollo de la habilidad oral del idioma inglés. El cuerpo teórico de la estrategia didáctica "MORE SPEAKING" se le sistematizó dotándole de una finalidad, de procesos didácticos y de un soporte teórico basado en el fundamento filosófico, psicológico y pedagógico. La población estudiada lo conforman 88 educandos y la muestra 25 educandos a quienes se les evaluó mediante un pre test y post test para determinar la influencia significativa o no de la estrategia didáctica "MORE SPEAKING" en el desarrollo de la habilidad oral del idioma inglés. Para medir la estrategia didáctica de los estudiantes del sexto grade "B" se aplicó una prueba de pre test al inicio y post test al final de las seis estrategias pedagógicas, el cual estuvo compuesto de 30 ítems dividido en cuatro componentes. El diseño de investigación fue pre-experimental con pre test y post test; con un grupo experimental, dichos grupos fueron intactas no equivalentes. Según lo demuestran los resultados estadísticos de la tabla Nº01 donde se demuestra un gran progreso entre el Pre-test y el Post-test. Por esta razón en los resultados de la prueba de hipótesis según el cuadro Nº 6 rechaza la hipótesis nula y se acepta la hipótesis de investigación. Es decir que la aplicación de la estrategia didáctica "MORE SPEAKING" incremento significativamente el desarrollo de la habilidad oral del idioma inglés en los alumnos del sexto gado "B" nivel primario de la l.E. 0620-Aplicacion del distrito de Tarapoto-211.Tesi