Roadmap to DILI research in Europe. A proposal from COST action ProEuroDILINet

In the current article the aims for a constructive way forward in Drug-Induced Liver Injury (DILI) are to highlight the most important priorities in research and clinical science, therefore supporting a more informed, focused, and better funded future for European DILI research. This Roadmap aims to identify key challenges, define a shared vision across all stakeholders for the opportunities to overcome these challenges and propose a high-quality research program to achieve progress on the prediction, prevention, diagnosis and management of this condition and impact on healthcare practice in the field of DILI. This will involve 1. Creation of a database encompassing optimised case report form for prospectively identified DILI cases with well-characterised controls with competing diagnoses, biological samples, and imaging data; 2. Establishing of preclinical models to improve the assessment and prediction of hepatotoxicity in humans to guide future drug safety testing; 3. Emphasis on implementation science and 4. Enhanced collaboration between drug-developers, clinicians and regulatory scientists. This proposed operational framework will advance DILI research and may bring together basic, applied, translational and clinical research in DILI.Funding for open access charge: Universidad de Malaga/CBUA. The present study has been supported by grants from Instituto de Salud Carlos III (ISCIII) (contract numbers: PID2022–140169OB-C21; PI21/01248; PI19/00883) and from Consejería de Salud de Andalucía (contract number: PEMP-0127–2020, Spain), cofounded by the European Union. This research was funded by HORIZON-HLTH-2022-STAYHLTH-02, grant number 101095679. Funded by the European Union. Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union. Neither the European Union nor the granting authority can be held responsible for them. MK was partially supported by Grant UID/BIM/0009/2020 of the Portuguese Fundação para a Ciência e a Tecnologia (FCT). MVP and IAA hold Sara Borrell research contracts from ISCIII (CD21/00198 and CD20/00083, respectively). This research was supported by CIBERehd – Consorcio Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – European Regional Development Fund. JIG and GPA are supported by NIHR Nottingham Biomedical Research Centre [NIHR203310]. The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. This publication is based upon work from COST Action “CA17112—Prospective European Drug-Induced Liver Injury Network” supported by COST (European Cooperation in Science and Technology); www.cost.eu

Roadmap to DILI research in Europe. A proposal from COST action ProEuroDILINet

In the current article the aims for a constructive way forward in Drug-Induced Liver Injury (DILI) are to highlight the most important priorities in research and clinical science, therefore supporting a more informed, focused, and better funded future for European DILI research. This Roadmap aims to identify key challenges, define a shared vision across all stakeholders for the opportunities to overcome these challenges and propose a high-quality research program to achieve progress on the prediction, prevention, diagnosis and management of this condition and impact on healthcare practice in the field of DILI. This will involve 1. Creation of a database encompassing optimised case report form for prospectively identified DILI cases with well-characterised controls with competing diagnoses, biological samples, and imaging data; 2. Establishing of preclinical models to improve the assessment and prediction of hepatotoxicity in humans to guide future drug safety testing; 3. Emphasis on implementation science and 4. Enhanced collaboration between drug-developers, clinicians and regulatory scientists. This proposed operational framework will advance DILI research and may bring together basic, applied, translational and clinical research in DILI.The present study has been supported by grants from Instituto de Salud Carlos III (ISCIII) (contract numbers: PID2022–140169OB-C21; PI21/01248; PI19/00883) and from Consejería de Salud de Andalucía (contract number: PEMP-0127–2020, Spain), cofounded by the European Union. This research was funded by HORIZON-HLTH-2022-STAYHLTH-02, grant number 101095679. Funded by the European Union. Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union. Neither the European Union nor the granting authority can be held responsible for them. MK was partially supported by Grant UID/BIM/0009/2020 of the Portuguese Fundação para a Ciência e a Tecnologia (FCT). MVP and IAA hold Sara Borrell research contracts from ISCIII (CD21/00198 and CD20/00083, respectively). This research was supported by CIBERehd – Consorcio Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – European Regional Development Fund. JIG and GPA are supported by NIHR Nottingham Biomedical Research Centre [NIHR203310]. The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. This publication is based upon work from COST Action “CA17112—Prospective European Drug-Induced Liver Injury Network” supported by COST (European Cooperation in Science and Technology); www.cost.eu.Peer reviewe

Síndrome de Cotard puerperal tras parto pretermino

Los cambios hormonales que ocurren durante el embarazo, parto y puerperio junto con los cambios psicológicos y sociales que tienen lugar en la mujer, la hacen más vulnerable y contribuyen al desarrollo de patología afectiva. La clínica puede ir desde la forma leve de tristeza postparto hasta las formas graves de  psicosis puerperal incluyendo la depresión delirante postparto. Sin embargo, es poco frecuente que la  depresión postparto con síntomas psicóticos se presente con delirios nihilistas como ocurre en el síndrome de Cotard. Por otro lado, es de sobra conocido que el estrés materno puede tener efectos nocivos en el  desarrollo fetal y en el curso del embarazo, asociándose en algunas ocasiones a complicaciones obstétricas como el crecimiento intraútero retardado y el parto pretérmino entre otros. Presentamos el caso de una paciente de 26 años de edad con antecedentes de tristeza postparto y aborto  previo, que durante el embarazo presenta rumiaciones cognitivas hipocondríacas y tristeza reactiva. El  embarazo finaliza con una cesárea urgente por pérdida del bienestar fetal, tras la cual desarrolla un episodio de depresión postparto con síntomas psicóticos caracterizados por ideas delirantes de vacío y de podredumbre que precisa ingreso hospitalario y tratamiento con antidepresivos y antipsicóticos

Depresión post ictus: una actualización

Resumen: Introducción: La depresión post ictus (DPI) es el trastorno afectivo más frecuente tras un ictus y el principal factor que limita la recuperación y rehabilitación de los pacientes, además de poder incrementar su mortalidad hasta 10 veces. Desarrollo: La DPI se presenta en uno de cada 3 pacientes con ictus y en más de la mitad de los casos no se diagnostica ni se trata. En su etiopatogenia son varios los mecanismos implicados: biológicos, conductuales y sociales.Los síntomas suelen aparecer en los primeros 3 meses tras el ictus (DPI «precoz») y menos frecuentemente más tarde (DPI «tardía»). Los síntomas son similares a los de otras depresiones, aunque con algunas diferencias, como presentar más trastornos del sueño, síntomas vegetativos e introversión para las relaciones sociales.Para su diagnóstico se recomienda mantener una actitud vigilante y emplear herramientas diagnósticas específicas, como el Patient Health Questionaire-2 (PHQ-2).Finalmente, el tratamiento de elección son los inhibidores selectivos de la recaptación de serotonina (ISRS). No obstante, aún son muchas las cuestiones por resolver en el tratamiento de la DPI, como cuándo es el mejor momento para iniciar el tratamiento o el efecto de los antidepresivos sobre la cognición y la función motora, entre otros. Conclusiones: Los neurólogos desempeñan un papel fundamental en la recuperación de los enfermos con ictus. Es necesario que estén familiarizados con la detección temprana y el tratamiento de la DPI, para así facilitar la recuperación funcional del paciente, su reinserción social y la mejora en la calidad de vida del enfermo y su familia. Abstract: Introduction: Post-stroke depression (PSD) is the most common mood disorder following a stroke, and also the main factor limiting recovery and rehabilitation in stroke patients. In addition, it may increase mortality by up to ten times. Development: PSD occurs in 1 in 3 stroke patients and more than half of all cases are neither diagnosed nor treated. Several mechanisms, including biological, behavioral, and social factors, are involved in its pathogenesis. Symptoms usually occur within the first three months after stroke (early onset PSD), and less frequently at a later time (late onset PSD). Symptoms resemble those of other types of depression, although there are some differences: PSD patients experience more sleep disturbances, vegetative symptoms, and social withdrawal.For PSD diagnosis, we recommended vigilance and use of specific diagnostic tools such as the Patient Health Questionnaire-2 (PHQ-2). The treatments of choice are selective serotonin reuptake inhibitors (SSRI). However, there are still many unanswered questions in the treatment of PSD, such as the best time to start treatment or the effects of antidepressants on cognition and motor function, among others. Conclusions: Neurologists play a pivotal role in the care and management of patients recovering from stroke. They must be familiar with methods for early detection and treatment of PSD, as this can facilitate a patient's functional recovery and social reintegration, and improve quality of life for patients and their families. Palabras clave: Antidepresivos, Depresión post ictus, Enfermedad cerebrovascular, Ictus, Inhibidores selectivos de la recaptación de serotonina, Keywords: Antidepressants, Post-stroke depression, Cerebrovascular disease, Stroke, Selective serotonin reuptake inhibitor

Post-stroke depression: an update

Introduction: Post-stroke depression (PSD) is the most common mood disorder following a stroke, and also the main factor limiting recovery and rehabilitation in stroke patients. In addition, it may increase mortality by up to ten times. Development: PSD occurs in 1 in 3 stroke patients and more than half of all cases are neither diagnosed nor treated. Several mechanisms, including biological, behavioural, and social factors, are involved in its pathogenesis. Symptoms usually occur within the first three months after stroke (early onset PSD), and less frequently at a later time (late onset PSD). Symptoms resemble those of other types of depression, although there are some differences; PSD patients experience more sleep disturbances, vegetative symptoms, and social withdrawal. For PSD diagnosis, we recommended vigilance and use of specific diagnostic tools such as the Patient Health Questionnaire-2 (PHQ-2). The treatments of choice are selective serotonin reuptake inhibitors (SSRI). However, there are still many unanswered questions in the treatment of PSD, such as the best time to start treatment or the effects of antidepressants on cognition and motor function, among others. Conclusions: Neurologists play a pivotal role in the care and management of patients recovering from stroke. They must be familiar with methods for early detection and treatment of PSD, as this can facilitate a patient's functional recovery and social reintegration, and improve quality of life for patients and their families. Resumen: Introducción: La depresión post ictus (DPI) es el trastorno afectivo más frecuente tras un ictus y el principal factor que limita la recuperación y rehabilitación de los pacientes, además de poder incrementar su mortalidad hasta 10 veces. Desarrollo: La DPI se presenta en uno de cada 3 pacientes con ictus y en más de la mitad de los casos no se diagnostica ni se trata. En su etiopatogenia son varios los mecanismos implicados: biológicos, conductuales y sociales. Los síntomas suelen aparecer en los primeros 3 meses tras el ictus (DPI «precoz») y menos frecuentemente más tarde (DPI «tardía»). Los síntomas son similares a los de otras depresiones, aunque con algunas diferencias, como presentar más trastornos del suẽno, síntomas vegetativos e introversión para las relaciones sociales. Para su diagnóstico se recomienda mantener una actitud vigilante y emplear herramientas diagnósticas específicas, como el Patient Health Questionaire-2 (PHQ-2). Finalmente, el tratamiento de elección son los inhibidores selectivos de la recaptación de serotonina (ISRS). No obstante, aún son muchas las cuestiones por resolver en el tratamiento de la DPI, como cuándo es el mejor momento para iniciar el tratamiento o el efecto de los antidepresivos sobre la cognición y la función motora, entre otros. Conclusiones: Los neurólogos desempẽnan un papel fundamental en la recuperación de los enfermos con ictus. Es necesario que estén familiarizados con la detección temprana y el trata-miento de la DPI, para así facilitar la recuperación funcional del paciente, su reinserción social y la mejora en la calidad de vida del enfermo y su familia. Keywords: Antidepressants, Post-stroke depression, Cerebrovascular disease, Stroke, Selective serotonin reuptake inhibitors, Palabras clave: Antidepresivos, Depresión post ictus, Enfermedad cerebrovascular, Ictus, Inhibidores selectivos de la recaptación de serotonin