Impact of comorbidities on anti-TNF alpha response and relapse in patients with inflammatory bowel disease: the VERNE study

Objective: To evaluate the impact of comorbidities and extraintestinal manifestations of inflammatory bowel disease on the response of patients with inflammatory bowel disease to antitumour necrosis factor alpha (anti-TNFalpha) therapy. Design: Data from 310 patients (194 with Crohn's disease and 116 with ulcerative colitis) treated consecutively with the first anti-TNFalpha in 24 Spanish hospitals were retrospectively analysed. Univariate and multivariate logistic regression analyses were performed to assess the associations between inflammatory bowel disease comorbidities and extraintestinal manifestations with anti-TNFalpha treatment outcomes. Key clinical features, such as type of inflammatory bowel disease and concomitant treatments, were included as fixed factors in the model. Results: Multivariate logistic regression analyses (OR, 95% CI) showed that chronic obstructive pulmonary disease (2.67, 1.33 to 5.35) and hepato-pancreato-biliary diseases (1.87, 1.48 to 2.36) were significantly associated with primary non-response to anti-TNFalpha, as was the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn's disease). It was also found that myocardial infarction (3.30, 1.48 to 7.35) and skin disease (2.73, 1.42 to 5.25) were significantly associated with loss of response, along with the use of corticosteroids and the type of inflammatory bowel disease (ulcerative colitis vs Crohn's disease). Conclusions: Our results suggest that the presence of some comorbidities in patients with inflammatory bowel disease, such as chronic obstructive pulmonary disease and myocardial infarction, and of certain extraintestinal manifestations of inflammatory bowel disease, such as hepato-pancreato-biliary conditions and skin diseases, appear to be related to failure to anti-TNFalpha treatment. Therefore, their presence should be considered when choosing a treatment. Trial registration number: NCT02861118

"Seguridad de la administración de carboximaltosa férrica inmediatamente después de infliximab, en una sola sesión, en los pacientes con enfermedad inflamatoria intestinal con deficiencia de hierro: un estudio piloto"

Objetivo: Obtener datos preliminares de seguridad y eficacia acerca de la administración intravenosa (IV) de infliximab (IFX) y carboximaltosa de hierro (FCM) en pacientes con enfermedad inflamatoria intestinal (EII), en una única sesión de tratamiento. Métodos: Estudio piloto, prospectivo, no intervencionista, observacional, de dos fases para evaluar la seguridad y eficacia de la infusión con FCM inmediatamente después de IFX. Los pacientes con EII fueron reclutados de forma consecutiva en la consulta monográfica de EII en dos grupos. Los pacientes del grupo de control (n = 12) recibieron la infusión IV de FCM al día siguiente del IFX. Posteriormente, se reclutaron pacientes al grupo de sesión única (n = 33) donde recibieron el FCM justo después de la infusión IV de IFX, en el mismo día. Todos los pacientes recibieron IFX a dosis de 5 mg/kg. El FCM se administró 1000 mg en pacientes con anemia con restricción de hierro (IRA) o 500mg en pacientes con deficiencia de hierro sin anemia. Evaluación de la seguridad se realizó mediante el registro de eventos adversos (EA) durante e inmediatamente después de la infusión, 30 minutos después, y mediante el seguimiento a los 7 días y 8 semanas. Para la evaluación de la eficacia, los parámetros hematológicos fueron evaluados antes de la infusión de FCM (pre-FCM) y después de 8 semanas. Se evaluó el impacto económico de la administración en una única sesión de FCM e IFX. Resultados: Cuarenta y cinco pacientes fueron reclutados (35 enfermedad de Crohn, 10 colitis ulcerosa). Veintiuno pacientes recibieron 500 mg FCM y 24 1000 mg de FCM. La administración de FCM inmediatamente después de IFX es eficaz para corregir la deficiencia de hierro o IRA, como se muestra por la elevación en los parámetros hematológicos. No se informó de acontecimientos adversos durante la evaluación de la seguridad al final de la administración de FCM o IFX, 30 minutos, 7 días y 8 semanas después, tanto en el grupo control como en el grupo de sesión única. El coste total por paciente para la administración en una única sesión fue de 354,63 €; para los pacientes que recibieron IFX y FCM en días separados era 531,94 €, dando un ahorro de costes de 177,31 € por paciente. Conclusión: La administración en una única sesión de FCM después de IFX es segura y eficaz en pacientes con EII y puede ofrecer una buena relación coste-beneficio y mejorar la adherencia al tratamiento. A nuestro entender, este estudio es el primero en evaluar la administración de FCM e IFX en una sola sesión de tratamiento

Evaluation of Changes in Gut Microbiota in Patients with Crohn’s Disease after Anti-Tnfα Treatment: Prospective Multicenter Observational Study

Background: Crohn’s disease is believed to result from the interaction between genetic susceptibility, environmental factors and gut microbiota, leading to an aberrant immune response. The objectives of this study are to evaluate the qualitative and quantitative changes in the microbiota of patients with Crohn’s disease after six months of anti-tumor-necrosis factor (anti-TNFα) (infliximab or adalimumab) treatment and to determine whether these changes lead to the recovery of normal microbiota when compared to a control group of healthy subjects. In addition, we will evaluate the potential role of the Faecalibacterium prausnitzii/Escherichia coli and Faecalibacterium prausnitzii/Clostridium coccoides ratios as indicators of therapeutic response to anti-TNFα drugs. Methods/Design: This prospective multicenter observational study will comprise a total of 88 subjects: 44 patients with Crohn’s disease scheduled to start anti-TNFα treatment as described in the drug specifications to control the disease and 44 healthy individuals who share the same lifestyle and eating habits. The presence of inflammatory activity will be determined by the Harvey-Bradshaw index, analytical parameters in blood, including C-reactive protein, and fecal calprotectin levels at commencement of the study, at three months and at six months, allowing the classification of patients into responders and non-responders. Microbiota composition and the quantitative relationship between Faecalibacterium prausnitzii and Escherichia coli and between Faecalibacterium prausnitzii and Clostridium coccoides group as indicators of dysbiosis will be studied at inclusion and six months after initiation of treatment using ultra sequencing with Illumina technology and comparative bioinformatics analysis for the former relationship, and digital droplet PCR using stool samples for the latter. Upon inclusion, patients will complete a survey of dietary intake for the three days prior to stool collection, which will be repeated six months later in a second collection to minimize dietary bias. Discussion: In this study, massive sequencing, a reliable new tool, will be applied to identify early biomarkers of response to anti-TNF treatment in patients with Crohn’s disease to improve clinical management of these patients, reduce morbidity rates and improve efficiency

Effect of an Immune-Boosting, Antioxidant and Anti-Inflammatory Food Supplement in Hospitalized COVID-19 Patients: A Prospective Randomized Pilot Study

Background: COVID-19 disease is a serious global health problem. Few treatments have been shown to reduce mortality and accelerate time to recovery. The aim of this study was to evaluate the potential effect of a food supplement (probiotics, prebiotics, vitamin D, zinc and selenium) in patients admitted with COVID-19. Methods: A prospective randomized non-blinded clinical trial was conducted in a sample of 162 hospitalized patients diagnosed with COVID-19 recruited over eight months. All patients received standard treatment, but the intervention group (n = 67) was given one food supplement stick daily during their admission. After collecting the study variables, a statistical analysis was performed comparing the intervention and control groups and a multivariate analysis controlling for variables that could act as confounding factors. Results: ROC curve analysis with an area under the curve (AUC) value of 0.840 (p p = 0.001); patients with non-severe disease on chest X-ray had shorter hospital stays: 8.1 ± 3.9 vs. 11.6 ± 7.4 days (p = 0.007). Conclusions: In this trial, the administration of a food supplement (Gasteel Plus®) was shown to be a protective factor in the group of patients with severe COVID-19 and allowed early recovery from digestive symptoms and a shorter hospital stay in patients with a normal–mild–moderate chest X-ray at admission (ClinicalTrials.gov number, NCT04666116)

Buenas Prácticas docentes/discentes de motivación y participación del aprendizaje

Actualmente se ha producido un cambio social importante en las aulas de la Universidad, donde se observa que una buena parte del alumnado no presta atención, interés y menos el planteamiento de dudas sobre lo expuesto por el profesor. La exposición tradicional mediante diapositivas, pizarra o lectura del tema, conduce al alumnado a mantener su interés menos de 1/3 de la duración de la clase. Este cambio debe plantearse en las aulas y en los nuevos enfoques del aprendizaje, dejando ser al estudiante sujeto totalmente activo, tanto en la búsqueda de conocimientos como en su evaluación, seguido y guiado por la experiencia del profesor. Desarrollamos la estrategia de que el alumno formule preguntas de cada tema antes de clase. Por todo ello se ha diseñado este proyecto, en 4 grados de Ciencias de la Salud, y en 4 universidades diferentes. En nuestro caso el equipo está formado por profesorado de asignaturas de los grados de Enfermería y Nutrición (UA), Medicina (UMH) y Medicina (Universidad Cardenal Herrera Valencia) y Enfermeria y Fisioterapia de la Universidad Cardenal Herrera CEU de Elche. Planteamos conocer hábitos de estudio en Ciencias de la Salud e implementar estrategias para motivar al alumno en su propio aprendizaje

Buenas Prácticas docentes/discentes de motivación y participación del aprendizaje

Actualmente se ha producido un cambio social importante en las aulas de la Universidad, donde se observa que una buena parte del alumnado no presta atención, interés y menos el planteamiento de dudas sobre lo expuesto por el profesor. La exposición tradicional mediante diapositivas, pizarra o lectura del tema, conduce al alumnado a mantener su interés menos de 1/3 de la duración de la clase. Este cambio debe plantearse en las aulas y en los nuevos enfoques del aprendizaje, dejando ser al estudiante sujeto totalmente activo, tanto en la búsqueda de conocimientos como en su evaluación, seguido y guiado por la experiencia del profesor. Desarrollamos la estrategia de que el alumno formule preguntas de cada tema antes de clase. Por todo ello se ha diseñado este proyecto, en 4 grados de Ciencias de la Salud, y en 4 universidades diferentes. En nuestro caso el equipo está formado por profesorado de asignaturas de los grados de Enfermería y Nutrición (UA), Medicina (UMH) y Medicina (Universidad Cardenal Herrera Valencia) y Enfermeria y Fisioterapia de la Universidad Cardenal Herrera CEU de Elche. Planteamos conocer hábitos de estudio en Ciencias de la Salud e implementar estrategias para motivar al alumno en su propio aprendizaje

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)