Perfil de seguridad de nirmatrelvir-ritonavir: evidencia de eventos adversos por interacciones farmacológicas / Safety profile of nirmatrelvir-ritonavir: Evidence of adverse events due to drug-drug interactions

Objetivo: evaluar el perfil de seguridad de nirmatrelvir-ritonavir (NMV-r) en la práctica clínica real y analizar la relevancia clínica de las interacciones farmacológicas en el desarrollo de eventos adversos. Material y métodos: estudio observacional, retrospectivo en el que se evaluaron los datos de seguridad de pacientes tratados con NMV-r entre abril y julio de 2022. Se recopilaron datos demográficos y analíticos antes de comenzar el tratamiento. La duración del seguimiento fue de 28 días y se evaluó el número reacciones adversas reportadas, así como si fueron manejadas de forma ambulatoria o precisaron de asistencia sanitaria especializada y la presencia de deterioro de la función renal y hepática. Se revisó el tratamiento concomitante, identificando interacciones farmacológicas teóricas (IFT) cuya gravedad fue definida mediante la clasificación Lexi-interact. Resultados: el estudio incluyó 146 pacientes, 82 (56,16 %) eran mujeres, cuya mediana de edad fue de 65 años (22-95). El número de IFT detectadas y mantenidas durante el tratamiento con NMV-r fue de 164, siendo el porcentaje de pacientes con al menos una interacción de 62,33%. La mediana de IFT por paciente fue de uno (0-5). En 18 pacientes (11,84%) se reportó al menos un evento adverso (EA). Once EA se relacionaron potencialmente con alguna IFT, 7 pacientes requirieron contacto con asistencia hospitalaria para el manejo del EA, 8 pacientes presentaron deterioro de la función renal y 2 de la función hepática a los 28 días. Los principales grupos de fármacos implicados en la aparición de algún EA fueron los anticoagulantes orales, así como los calcio-antagonistas. Conclusiones: nuestros resultados muestran un elevado número de IFT detectadas entre NMV-r y otros fármacos, aunque la frecuencia de EA asociados fue baja. Este estudio proporciona un mayor conocimiento de los fármacos implicados en dichas interacciones y su potencial relación con la aparición de EA.(AU)

Objective: The aim of the study was to evaluate the safety profile of nirmatrelvir-ritonavir (NMV-r) in real clinical practice and to analyze the clinical relevance of drug-drug interactions in the development of adverse events. Methods: Observational, retrospective study in which safety data of patients treated with NMV-r between April and July 2022 in an outpatient setting were evaluated. The duration of follow-up was 28 days and the number of adverse reactions reported, as well as whether they were managed on an outpatient basis or required health care, and the presence of renal and hepatic function impairment were assessed. Concomitant treatment was reviewed, identifying theoretical drug-drug interactions (TDDIs) whose severity was defined using the Lexi-interact classification. Results: The study included 146 patients, 82 (56,16%) were women, whose median age was 65 years (22-95). The number of TDDIs detected and maintained during treatment with NMV-r was 164, with the percentage of patients with at least one interaction being 62,33%. The median number of TDDIs per patient was 1 (0-5). At least 1 adverse event (AE) was reported in 18 patients (11,84%). Eleven AEs were potentially related to any TDDI. Seven patients required contact with hospital assistance for AE management. Eight patients had impaired renal function and 2 had impaired liver function at 28 days. The main groups of drugs implicated in the occurrence of an AE were oral anticoagulants and calcium antagonists. Conclusions: Our results show a high number of TDDIs detected were detected between NMV-r and other drugs. This study provides greater knowledge of the drugs involved in such interactions and their potential relationship with the occurrence of adverse events.(AU)

Safety profile of nirmatrelvir-ritonavir: Evidence of adverse events due to DDIs / Perfil de seguridad de nirmatrelvir-ritonavir: evidencia de eventos adversos por interacciones farmacológicas

Objetivo: evaluar el perfil de seguridad de nirmatrelvir-ritonavir (NMV-r) en la práctica clínica real y analizar la relevancia clínica de las interacciones farmacológicas en el desarrollo de eventos adversos. Material y métodos: estudio observacional, retrospectivo en el que se evaluaron los datos de seguridad de pacientes tratados con NMV-r entre abril y julio de 2022. Se recopilaron datos demográficos y analíticos antes de comenzar el tratamiento. La duración del seguimiento fue de 28 días y se evaluó el número reacciones adversas reportadas, así como si fueron manejadas de forma ambulatoria o precisaron de asistencia sanitaria especializada y la presencia de deterioro de la función renal y hepática. Se revisó el tratamiento concomitante, identificando interacciones farmacológicas teóricas (IFT) cuya gravedad fue definida mediante la clasificación Lexi-interact. Resultados: el estudio incluyó 146 pacientes, 82 (56,16 %) eran mujeres, cuya mediana de edad fue de 65 años (22-95). El número de IFT detectadas y mantenidas durante el tratamiento con NMV-r fue de 164, siendo el porcentaje de pacientes con al menos una interacción de 62,33%. La mediana de IFT por paciente fue de uno (0-5). En 18 pacientes (11,84%) se reportó al menos un evento adverso (EA). Once EA se relacionaron potencialmente con alguna IFT, 7 pacientes requirieron contacto con asistencia hospitalaria para el manejo del EA, 8 pacientes presentaron deterioro de la función renal y 2 de la función hepática a los 28 días. Los principales grupos de fármacos implicados en la aparición de algún EA fueron los anticoagulantes orales, así como los calcio-antagonistas. Conclusiones: nuestros resultados muestran un elevado número de IFT detectadas entre NMV-r y otros fármacos, aunque la frecuencia de EA asociados fue baja. Este estudio proporciona un mayor conocimiento de los fármacos implicados en dichas interacciones y su potencial relación con la aparición de EA.(AU)

Objective: The aim of the study was to evaluate the safety profile of nirmatrelvir-ritonavir (NMV-r) in real clinical practice and to analyze the clinical relevance of drug-drug interactions in the development of adverse events. Methods: Observational, retrospective study in which safety data of patients treated with NMV-r between April and July 2022 in an outpatient setting were evaluated. The duration of follow-up was 28 days and the number of adverse reactions reported, as well as whether they were managed on an outpatient basis or required health care, and the presence of renal and hepatic function impairment were assessed. Concomitant treatment was reviewed, identifying theoretical drug-drug interactions (TDDIs) whose severity was defined using the Lexi-interact classification. Results: The study included 146 patients, 82 (56,16%) were women, whose median age was 65 years (22-95). The number of TDDIs detected and maintained during treatment with NMV-r was 164, with the percentage of patients with at least one interaction being 62,33%. The median number of TDDIs per patient was 1 (0-5). At least 1 adverse event (AE) was reported in 18 patients (11,84%). Eleven AEs were potentially related to any TDDI. Seven patients required contact with hospital assistance for AE management. Eight patients had impaired renal function and 2 had impaired liver function at 28 days. The main groups of drugs implicated in the occurrence of an AE were oral anticoagulants and calcium antagonists. Conclusions: Our results show a high number of TDDIs detected were detected between NMV-r and other drugs. This study provides greater knowledge of the drugs involved in such interactions and their potential relationship with the occurrence of adverse events.(AU)

Análisis de eventos adversos en los servicios de cirugía general y aparato digestivo. Estudio multicéntrico / Analysis of adverse events in general surgery: A multicenter study

Introducción: El conocimiento de los eventos adversos (EA) en los hospitales de agudos es un aspecto de especial relevancia en la seguridad del paciente. Su incidencia oscila entre un 3-17% y la cirugía se relaciona con la aparición de entre un 46-65% de todos los EA. Material y métodos: Se realiza un estudio observacional, descriptivo, retrospectivo y multicéntrico, con la participación de 31 hospitales de agudos españoles, para la determinación y análisis de los EA en los servicios de cirugía general. Resultados: La prevalencia de EA fue del 31,53%. Los tipos de EA más frecuentes fueron de tipo infeccioso (35%). Los pacientes con mayores grados de ASA, mayor complejidad y un tipo de ingreso urgente son factores asociados a la presencia de EA. A la mayoría de los pacientes se les atribuyó una categoría de daño F (daño temporal al paciente que requiera iniciar o prolongar la hospitalización) (58,42%). El 14,69% de los EA son considerados graves. El 34,22% de los EA se consideraron evitables. Conclusiones: La prevalencia de EA en los pacientes de cirugía general y del aparato digestivo (CGAD) es elevada. La mayor parte de los EA fueron de tipo infeccioso. El EA más frecuente fue la infección de herida o sitio quirúrgico. Los pacientes con mayores grados de ASA, mayor complejidad y un tipo de ingreso urgente son factores asociados a la presencia de EA. La mayoría de los EA detectados han supuesto un daño leve o moderado sobre los pacientes. Alrededor de un tercio de EA fueron evitables.(AU)

Introduction: Knowledge of adverse events (AE) in acute care hospitals is a particularly relevant aspect of patient safety. Its incidence ranges from 3% to 17%, and surgery is related to the occurrence of 46%-65% of all AE. Material and methods: An observational, descriptive, retrospective, multicenter study was conducted with the participation of 31 Spanish acute-care hospitals to determine and analyze AE in general surgery services. Results: The prevalence of AE was 31.53%. The most frequent types of AE were infectious (35%). Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. The majority of patients (58.42%) were attributed a category F event (temporary harm to the patient requiring initial or prolonged hospitalization); 14.69% of AE were considered severe, while 34.22% of AE were considered preventable. Conclusions: The prevalence of AE in General and GI Surgery (GGIS) patients is high. Most AE were infectious, and the most frequent AE was surgical site infection. Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. Most detected AE resulted in mild or moderate harm to the patients. About one-third of AE were preventable.(AU)

Analysis of adverse events in general surgery. Multicenter study.

INTRODUCTION: Knowledge of adverse events (AE) in acute care hospitals is a particularly relevant aspect of patient safety. Its incidence ranges from 3% to 17%, and surgery is related to the occurrence of 46%-65% of all AE. MATERIAL AND METHODS: An observational, descriptive, retrospective, multicenter study was conducted with the participation of 31 Spanish acute-care hospitals to determine and analyze AE in general surgery services. RESULTS: The prevalence of AE was 31.53%. The most frequent types of AE were infectious (35%). Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. The majority of patients (58.42%) were attributed a category F event (temporary harm to the patient requiring initial or prolonged hospitalization); 14.69% of AE were considered severe, while 34.22% of AE were considered preventable. CONCLUSIONS: The prevalence of AE in General and GI Surgery (GGIS) patients is high. Most AE were infectious, and the most frequent AE was surgical site infection. Higher ASA grades, greater complexity and urgent-type admission are factors associated with the presence of AE. Most detected AE resulted in mild or moderate harm to the patients. About one-third of AE were preventable.

Implementation of esophageal endoscopic submucosal dissection in Spain: Results from the nationwide registry. / Implementación de la disección endoscópica submucosa esofágica en España: resultados del registro nacional.

INTRODUCTION AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) in the esophagus have not been assessed in our country. Our primary aim was to analyze the effectiveness and safety of the technique. MATERIAL AND METHODS: Analysis of the prospectively maintained national registry of ESD. We included all superficial esophageal lesions removed by ESD in 17 hospitals (20 endoscopists) between January 2016 and December 2021. Subepithelial lesions were excluded. The primary outcome was curative resection. We conducted a survival analysis and used logistic regression analysis to assess predictors of non-curative resection. RESULTS: A total of 102 ESD were performed on 96 patients. The technical success rate was 100% and the percentage of en-bloc resection was 98%. The percentage of R0 and curative resection was 77.5% (n=79; 95%CI: 68%-84%) and 63.7% (n=65; 95%CI: 54%-72%), respectively. The most frequent histology was Barrett-related neoplasia (n=55 [53.9%]). The main reason for non-curative resection was deep submucosal invasion (n=25). The centers with a lower volume of ESD obtained worse results in terms of curative resection. The rate of perforation, delayed bleeding and post-procedural stenosis were 5%, 5% and 15.7%, respectively. No patient died or required surgery due to an adverse effect. After a median follow-up of 14months, 20patients (20.8%) underwent surgery and/or chemoradiotherapy, and 9 patients died (mortality 9.4%). CONCLUSIONS: In Spain, esophageal ESD is curative in approximately two out of three patients, with an acceptable risk of adverse events.

Fatores associados ao comprometimento da segurança do paciente na unidade de terapia intensiva / Factors associated with the commitment of patient safety in the intensive care unit / Factores asociados al compromiso de la seguridad del paciente en la unidad de cuidados intensivos

Objetivo: conhecer os fatores associados ao comprometimento da segurança do paciente. Método: trata-se de um artigo de revisão integrativa da literatura a partir das bases de dados Scientific Electrônic Library Online, PubMed e Literatura Latino-americana e do Caribe em Ciências da Saúde, realizada entre abril e maio de 2022. Resultados: foi visto os principais fatores que corroboram para o comprometimento da segurança, sendo a utilização inadequada dos equipamentos, falta de rotina e ausência de protocolo no setor. Foi detectado a problemática da carga exacerbada de trabalho. Conflitos na equipe também foi tido como um preditor para existência de evento adverso. E por fim, o quesito da subnotificação dos erros. Conclusão: é visto a necessidade da gestão reverter esses problemas, para que a assim a porcentagem de erros seja diminuída.

Objective: to know the factors associated with compromised patient safety. Method: this is an integrative literature review article based on the Scientific Electronic Library Online, PubMed and Latin American and Caribbean Literature in Health Sciences databases, carried out between April and May 2022. Results: it was seen the main factors that corroborate for the compromise of safety, being the inadequate use of equipment, lack of routine and lack of protocol in the sector. The problem of exacerbated workload was detected. Conflicts in the team was also considered a predictor for the existence of an adverse event. And finally, the issue of underreporting of errors. Conclusion: the need for management to reverse these problems is seen, so that the percentage of errors is reduced.

Objetivos:conocer los factores asociados a la seguridad del paciente comprometida. Método: este es un artículo de revisión integradora de la literatura basado en las bases de datos Scientific Electronic Library Online, PubMed y Latin American and Caribbean Literature in Health Sciences, realizado entre abril y mayo de 2022. Resultados: se vieron los principales factores que corroboran para el compromiso de seguridad, siendo el uso inadecuado de equipos, falta de rutina y falta de protocolo en el sector. Se detectó el problema de la sobrecarga de trabajo. Los conflictos en el equipo también fueron considerados predictores de la existencia de un evento adverso. Y por último, el tema del subregistro de errores. Conclusión: se ve la necesidad de que la gestión revierta estos problemas, de modo que se reduzca el porcentaje de errores.

Headache as the most prevalent post-vaccination adverse event after Covid-19 vaccination / Dor de cabeça como evento adverso pós-vacinação mais prevalente após a vacinação contra Covid-19

BACKGROUND: In 2020, the first vaccines were approved, according to the WHO. However, speculations arose regarding their efficacy and post-vaccination adverse events (AEFV). OBJECTIVE: To evaluate the prevalence of headache as AEFI from the SARSCoV-2 vaccine in Piauí, Brazil. METHODS: This is a quantitative, observational, cross-sectional, and prevalence study. Data were provided by the Post-Vaccination Adverse Event Information System (SI-AEFV), from reported cases from January to September 2021. Data were analyzed, and the research was approved by the UFPI Research Ethics Committee. RESULTS: A total of 2,008 cases were analyzed. Headache was reported in 752 cases (27.99%) as an AEFV after vaccination against SARS-CoV-2. In most cases, patients were from Teresina (67.62%), of brown race/ethnicity (52.67%), female (79.00%), and the majority were not healthcare professionals (54.27%). The most common age of patients, with the original data, was 33 years. After data correction, the most common age was 28 years. The majority of these cases were not severe (96.44%), and the majority of cases were associated with the first dose of the Covid-19-Covishield-Oxford/AstraZeneca vaccine (43.18%).CONCLUSION: Thus, it is concluded from the partial analysis of the results that headache is the most common adverse event after vaccination against SARS-CoV-2. The profile of patients with the most notifications was brown women aged 30 to 40 years who received the first dose of the Covid-19-Covishield-Oxford/AstraZeneca vaccine. Regarding the severity of events, the vast majority were considered non-severe, and no deaths were mentioned, demonstrating the safety of immunobiologicals.

FUNDAMENTO: Em 2020, foram aprovadas as primeiras vacinas, segundo a OMS. No entanto, surgiram especulações quanto à sua eficácia e eventos adversos pós-vacinais (EAPV). OBJETIVO: Avaliar a prevalência de cefaleia como EAPV da vacina SARSCoV-2 no Piauí, Brasil. MÉTODOS: Trata-se de um estudo quantitativo, observacional, transversal e de prevalência. Os dados foram fornecidos pelo Sistema de Informação de Eventos Adversos Pós-Vacinação (SI-AEFV), dos casos notificados no período de janeiro a setembro de 2021. Os dados foram analisados ​​e a pesquisa foi aprovada pelo Comitê de Ética em Pesquisa da UFPI. RESULTADOS: Foram analisados ​​2.008 casos. Cefaleia foi relatada em 752 casos (27,99%) como EAPV após vacinação contra SARS-CoV-2. Na maioria dos casos, os pacientes eram procedentes de Teresina (67,62%), de raça/etnia parda (52,67%), do sexo feminino (79,00%) e a maioria não era profissional de saúde (54,27%). A idade mais comum dos pacientes, com os dados originais, era de 33 anos. Após correção dos dados, a idade mais comum foi 28 anos. A maioria desses casos não foi grave (96,44%), e a maioria dos casos esteve associada à primeira dose da vacina Covid-19-Covishield-Oxford/AstraZeneca (43,18%).CONCLUSÃO: Assim, conclui-se a partir da análise parcial dos resultados de que cefaleia é o evento adverso mais comum após vacinação contra SARS-CoV-2. O perfil dos pacientes com mais notificações foi de mulheres pardas com idade entre 30 e 40 anos que receberam a primeira dose da vacina Covid-19-Covishield-Oxford/AstraZeneca. Quanto à gravidade dos eventos, a grande maioria foi considerada não grave e não foram mencionados óbitos, demonstrando a segurança dos imunobiológicos.

Evaluation of tolerance to mercaptopurine in patients with inflammatory bowel disease and gastrointestinal intolerance to azathioprine.

BACKGROUND: Thiopurines such as azathioprine (AZA) and mercaptopurine (MP) are commonly utilized to treat inflammatory bowel disease (IBD). Their use is frequently restricted due to gastrointestinal intolerance (GI). Previous retrospective studies have reported that AZA-intolerant patients may benefit from a switch to MP; yet the effectiveness of this strategy has not been prospectively evaluated. AIMS: To assess GI tolerance to MP in patients who are intolerant to AZA, and to identify clinical predictors of GI intolerance to AZA or MP. METHODS: A prospective, observational, single-cohort study was performed in 92 thiopurine-naïve IBD patients. They were started on a 50mg dose of AZA and escalated to 2.5mg/kg per day by week 2. Those with GI intolerance were rechallenged with a 50% dose of AZA, after which another dose escalation attempt was made. If symptoms persisted, they were switched to MP. RESULTS: Thirty (32.6%) of the recruited patients suffered from GI intolerance to AZA. Of these, 15 did not present recurrence of symptoms after rechallenge with lower doses. Of 15 intolerant patients, 14 were switched to MP. Within the MP cohort, 8 patients (57%) were also intolerant to MP, 5 (36%) had no symptoms, and 1 (7%) was lost to follow-up. Female gender was the only independent predictor of GI intolerance to AZA. CONCLUSIONS: Up to half of the AZA-intolerant patients tolerated a 50% dose rechallenge that was successfully escalated. A switch to MP was tolerated in over a third of cases whom rechallenge failed. Our strategy (challenge-rechallenge-switch) achieved an overall GI tolerance to thiopurines in most of the patients.

Sistemas de notificación de eventos adversos como estrategia para la cultura de calidad y seguridad del paciente / Adverse event reporting systems as a strategy for a culture of quality and patient safety

Introducción: el objetivo de los Sistemas de Notificación de Eventos Adversos, Eventos Centinela y Cuasifallas, es conocer la frecuencia con la que se presentan y generar las estrategias para su disminución y la no repetición de dichos eventos. Se debe informar al personal de salud involucrado en los procesos de atención, principalmente a quienes tienen contacto directo con los pacientes. Desarrollo: se realizó una revisión bibliográfica conceptual y de investigación sobre los sistemas de notificación de eventos adversos. La búsqueda y selección de artículos publicados de 2016 a 2021, fue en la base de datos PubMed y el índice de revistas de acceso abierto Medigraphic, mediante los siguientes criterios de búsqueda en español e inglés: sistemas de notificación, evento adverso, evento centinela, sistema VENCER, Instituto Mexicano del Seguro Social, Secretaría de Salud; así como el uso del operador booleano AND: Notificatión AND adverse event, notification system AND sentinel event, adverse event AND quality plan. Se obtuvo un aproximado de 194 resultados, de los cuales se seleccionaron los artículos que se apegaban al objetivo de esta revisión. Conclusiones: con la presente revisión bibliográfica se muestra que la notificación de los eventos adversos por parte del personal de la salud involucrados en los procesos de atención, adquiere especial relevancia cuando ésta es proporcional a la adquisición de luna cultura de calidad y seguridad en la atención de los pacientes... (AU)

Abstract Introduction: The objective of the Notification Systems for Adverse Events, Sentinel Events and Near Failures is to know the frequency with which they occur and to generate strategies for their reduction and non-repetition of said events. Health personnel involved in the care processes should be informed, mainly those who have direct contact with patients. Development: A conceptual and research literature review on adverse event reporting systems was carried out. The search and selection of articles published from 2016 to 2021 was in the PubMed database and the Medigraphic open access journal index, using the following search criteria in Spanish and English: notification systems, adverse event, sentinel event, VENCER system, Mexican Institute of Social Security, Ministry of Health, as well as the use of the boolean operator AND: Notification AND adverse event, notification system AND sentinel event, adverse event AND quality plan. An approximate of 194 results were obtained, from which the articles that met the objective of this review were selected. Conclusions: This bibliographic review shows that the notification of adverse events by health personnel involved in care processes acquires special relevance when it is proportional to the acquisition of a culture of quality and safety in care. from the patients.

Implicaciones jurídicas de los sistemas de notificación y registro de eventos adversos en la esfera sanitaria / [Legal implications of notification and registration systems for adverse events in the healthcare sphere]

La notificación de eventos adversos constituye uno de los instrumentos esenciales de cara a la consecución de mejoras significativas en materia de seguridad del paciente. El presente trabajo pretende concretar las implicaciones jurídicas de las pautas sentadas a nivel internacional (OMS, Consejo de Europa y UE) de cara al establecimiento de un marco legal nacional favorable a la notificación de eventos adversos en la esfera sanitaria. (AU)

The reporting of adverse events is one of the key elements in achieving significant improvements in the field of patient safety. Based on international guidelines (WHO, Council of Europe and EU) this paper aims to analyse their juridical implications when settling a national legal framework for reporting adverse events in the sphere of healthcare. (AU)

[Translated article] Safety profile of nirmatrelvir-ritonavir: Evidence of adverse events due to DDIs.

OBJECTIVE: The aim of the study was to evaluate the safety profile of nirmatrelvir-ritonavir (NMV-r) in real clinical practice and to analyse the clinical relevance of drug-drug interactions in the development of adverse events. METHODS: Observational, retrospective study in which safety data of patients treated with NMV-r between April and July 2022 in an outpatient setting were evaluated. The duration of follow-up was 28 days and the number of adverse reactions reported, as well as whether they were managed on an outpatient basis or required health care, and the presence of renal and hepatic function impairment were assessed. Concomitant treatment was reviewed, identifying theoretical drug-drug interactions (TDDIs) whose severity was defined using the Lexi-interact classification. RESULTS: The study included 146 patients. 82 (56.16%) were women, whose median age was 65 years (22-95). the number of TDDIs detected and maintained during treatment with NMV-r was 164, with the percentage of patients with at least 1 interaction being 62.33%. The median number of TDDIs per patient was 1 (0-5). At least 1 adverse event (AE) was reported in 18 patients (11.84%). 11 AEs were potentially related to any TDDI. 7 patients required contact with hospital assistance for AE management. 8 patients had impaired renal function and 2 had impaired liver function at 28 days. The main groups of drugs implicated in the occurrence of an AE were oral anticoagulants and calcium antagonists. CONCLUSIONS: Our results show a high number of TDDIs detected were detected between NMV-r and other drugs. This study provides greater knowledge of the drugs involved in such interactions and their potential relationship with the occurrence of adverse events.

Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders / Perfil de seguridad a largo plazo y usos fuera de indicación de los inhibidores de JAK en dermatología

JAK inhibitors target specific inflammatory cytokines involved in various inflammatory diseases. Four molecules have been approved for dermatological use: upadacitinib, baricitinib, abrocitinib and topical ruxolitinib. Off-label prescriptions for other dermatological conditions have been reported. We conducted a narrative review of the literature to assess the long-term safety profile of currently approved JAK inhibitors in dermatology, and their off-label use in skin disorders. We performed literature searches with Pubmed and Google Scholar from January 2000 to January 2023, using the keywords “Janus kinase inhibitors”, “JAK inhibitors”, “off-label”, “dermatology”, “safety”, “adverse events”, “ruxolitinib”, “upadacitinib”, “abrocitinib” and “baricitinib”. Our search yielded a total of 37 dermatological disorders with studies supporting the use of these JAK inhibitors. Preliminary studies indicate that JAK inhibitors generally have a favorable safety profile and can be considered as an option in many dermatological disorders (AU)

Los inhibidores de JAK actúan bloqueando la acción de ciertas citoquinas inflamatorias involucradas en varias enfermedades inflamatorias. Cuatro moléculas han sido aprobadas para uso en dermatología: upadacitinib, baricitinib, abrocitinib y ruxolitinib tópico. Se han reportado usos fuera de indicación para diferentes enfermedades dermatológicas. Se realizó una revisión narrativa de la literatura sobre la seguridad a largo plazo de los inhibidores de JAK aprobados en dermatología y su uso fuera de indicación en enfermedades dermatológicas, mediante búsquedas bibliográficas en Pubmed y Google Scholar desde enero de 2000 hasta enero de 2023, incluyendo las palabras clave: «Janus kinase inhibitors», «JAK inhibitors», «off-label», «dermatology», «safety», «adverse events», «ruxolitinib», «upadacitinib», «abrocitinib» y «baricitinib». Se encontraron un total de 37 trastornos dermatológicos con estudios que respaldan el uso de estos fármacos. Los estudios preliminares indican que los inhibidores de JAK tienen un perfil de seguridad generalmente favorable y pueden considerarse una opción en muchas enfermedades dermatológicas (AU)

[Artículo traducido] Perfil de seguridad a largo plazo y usos fuera de indicación de los inhibidores de JAK en dermatología / Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders

Los inhibidores de JAK actúan bloqueando la acción de ciertas citoquinas inflamatorias involucradas en varias enfermedades inflamatorias. Cuatro moléculas han sido aprobadas para uso en dermatología: upadacitinib, baricitinib, abrocitinib y ruxolitinib tópico. Se han reportado usos fuera de indicación para diferentes enfermedades dermatológicas. Se realizó una revisión narrativa de la literatura sobre la seguridad a largo plazo de los inhibidores de JAK aprobados en dermatología y su uso fuera de indicación en enfermedades dermatológicas, mediante búsquedas bibliográficas en Pubmed y Google Scholar desde enero de 2000 hasta enero de 2023, incluyendo las palabras clave: «Janus kinase inhibitors», «JAK inhibitors», «off-label», «dermatology», «safety», «adverse events», «ruxolitinib», «upadacitinib», «abrocitinib» y «baricitinib». Se encontraron un total de 37 trastornos dermatológicos con estudios que respaldan el uso de estos fármacos. Los estudios preliminares indican que los inhibidores de JAK tienen un perfil de seguridad generalmente favorable y pueden considerarse una opción en muchas enfermedades dermatológicas (AU)

JAK inhibitors target specific inflammatory cytokines involved in various inflammatory diseases. Four molecules have been approved for dermatological use: upadacitinib, baricitinib, abrocitinib and topical ruxolitinib. Off-label prescriptions for other dermatological conditions have been reported. We conducted a narrative review of the literature to assess the long-term safety profile of currently approved JAK inhibitors in dermatology, and their off-label use in skin disorders. We performed literature searches with Pubmed and Google Scholar from January 2000 to January 2023, using the keywords “Janus kinase inhibitors”, “JAK inhibitors”, “off-label”, “dermatology”, “safety”, “adverse events”, “ruxolitinib”, “upadacitinib”, “abrocitinib” and “baricitinib”. Our search yielded a total of 37 dermatological disorders with studies supporting the use of these JAK inhibitors. Preliminary studies indicate that JAK inhibitors generally have a favorable safety profile and can be considered as an option in many dermatological disorders (AU)

Versión en español de los criterios STOPP/START 3. Avances en la detección de la prescripción inapropiada de medicamentos en personas mayores / Spanish version of the STOPP/START 3 criteria: Advances in the detection of inappropriate prescribing medication in the older people

Los criterios STOPP/START son criterios explícitos basados en sistemas fisiológicos que resumen la evidencia sobre problemas de prescripción relevantes clínicamente relacionados con el uso de medicamentos potencialmente inapropiados (criterios STOPP) y con potenciales omisiones de prescripción (criterios START). Las dos versiones anteriores de los criterios STOPP/START se publicaron en 2008 y en 2015, y sus versiones en español, en 2009 y en 2015. En 2023 se acaba de publicar la versión3 de dichos criterios. El objetivo de este artículo es presentar la versión traducida al español, así como revisar la utilización y el impacto que ha tenido la versión2 del año 2015 en nuestro idioma. Se realizó una traducción del inglés al español por profesionales expertos y con alto nivel de inglés de la versión3 de los criterios STOPP/START, que incorporan la evidencia publicada desde abril de 2014 hasta marzo de 2022. Además, se hizo una revisión sistemática de las publicaciones que han usado la traducción española de la versión previa (versión2 de 2015) de los criterios STOPP/START. La nueva versión, presentada en este artículo, cuenta con 190 criterios STOPP/START (133 criterios STOPP y 57 criterios START), lo que supone un aumento del 40% en el número de criterios en comparación con la versión anterior. En la revisión se encontraron 37 estudios (21 observacionales, 11 de intervención y 5 de otro tipo) que han usado la versión española en lugar de la internacional. La versión3 en español de los criterios STOPP/START es una lista explícita actualizada de medicamentos potencialmente inapropiados y posibles omisiones en la prescripción que tienen el objetivo de optimizar la medicación y minimizar las reacciones adversas a los medicamentos durante la revisión de la medicación en las personas mayores, en particular aquellas con multimorbilidad y polifarmacia (AU)

The STOPP/START criteria are explicit physiologic systems-based criteria that summarize evidence on clinically relevant prescribing problems related to the use of potentially inappropriate medications (STOPP criteria) and potential prescribing omissions (START criteria). The two previous versions of the STOPP/START criteria were published in 2008 and 2015, and their Spanish versions in 2009 and 2015. Version3 of these criteria has just been published in 2023. The aim of this article is to present the Spanish translated version, and to review the use and impact that version2 of 2015 has had in our language. A translation from English to Spanish was performed by expert professionals with a high level of English of version3 of the STOPP/START criteria, which incorporates the evidence published from April 2014 to March 2022. In addition, a systematic review of publications that have used the Spanish translation of the previous version (version2 of 2015) of the STOPP/START criteria was performed. The new version, presented in this article, has 190 STOPP/START criteria (133 STOPP criteria and 57 START criteria), which is a 40% increase in the number of criteria compared to the previous version. The review found 37 studies (21 observational, 11 interventional and 5 other) that used the Spanish version instead of the international version. The Spanish version 3 of the STOPP/START criteria is an updated explicit list of potentially inappropriate medications and possible omissions in prescribing that aims to optimize medication and minimize adverse drug reactions during medication review in the elderly, particularly those with multimorbidity and polypharmacy (AU)

Safety profile of nirmatrelvir-ritonavir: Evidence of adverse events due to drug-drug interactions. / Perfil de seguridad de nirmatrelvir-ritonavir: evidencia de eventos adversos por interacciones farmacológicas.

OBJECTIVE: The aim of the study was to evaluate the safety profile of nirmatrelvir-ritonavir (NMV-r) in real clinical practice and to analyze the clinical relevance of drug-drug interactions in the development of adverse events. METHODS: Observational, retrospective study in which safety data of patients treated with NMV-r between April and July 2022 in an outpatient setting were evaluated. The duration of follow-up was 28 days and the number of adverse reactions reported, as well as whether they were managed on an outpatient basis or required health care, and the presence of renal and hepatic function impairment were assessed. Concomitant treatment was reviewed, identifying theoretical drug-drug interactions (TDDIs) whose severity was defined using the Lexi-interact classification. RESULTS: The study included 146 patients, 82 (56,16%) were women, whose median age was 65 years (22-95). The number of TDDIs detected and maintained during treatment with NMV-r was 164, with the percentage of patients with at least one interaction being 62,33%. The median number of TDDIs per patient was 1 (0-5). At least 1 adverse event (AE) was reported in 18 patients (11,84%). Eleven AEs were potentially related to any TDDI. Seven patients required contact with hospital assistance for AE management. Eight patients had impaired renal function and 2 had impaired liver function at 28 days. The main groups of drugs implicated in the occurrence of an AE were oral anticoagulants and calcium antagonists. CONCLUSIONS: Our results show a high number of TDDIs detected were detected between NMV-r and other drugs. This study provides greater knowledge of the drugs involved in such interactions and their potential relationship with the occurrence of adverse events.

[Spanish version of the STOPP/START 3 criteria: Advances in the detection of inappropriate prescribing medication in the older people]. / Versión en español de los criterios STOPP/START 3. Avances en la detección de la prescripción inapropiada de medicamentos en personas mayores.

The STOPP/START criteria are explicit physiologic systems-based criteria that summarize evidence on clinically relevant prescribing problems related to the use of potentially inappropriate medications (STOPP criteria) and potential prescribing omissions (START criteria). The two previous versions of the STOPP/START criteria were published in 2008 and 2015, and their Spanish versions in 2009 and 2015. Version3 of these criteria has just been published in 2023. The aim of this article is to present the Spanish translated version, and to review the use and impact that version2 of 2015 has had in our language. A translation from English to Spanish was performed by expert professionals with a high level of English of version3 of the STOPP/START criteria, which incorporates the evidence published from April 2014 to March 2022. In addition, a systematic review of publications that have used the Spanish translation of the previous version (version2 of 2015) of the STOPP/START criteria was performed. The new version, presented in this article, has 190 STOPP/START criteria (133 STOPP criteria and 57 START criteria), which is a 40% increase in the number of criteria compared to the previous version. The review found 37 studies (21 observational, 11 interventional and 5 other) that used the Spanish version instead of the international version. The Spanish version 3 of the STOPP/START criteria is an updated explicit list of potentially inappropriate medications and possible omissions in prescribing that aims to optimize medication and minimize adverse drug reactions during medication review in the elderly, particularly those with multimorbidity and polypharmacy. With this new version, the original criteria are intended to be more widely disseminated within the Spanish-speaking healthcare community. The Spanish version2 of the STOPP/START has been widely used, so we consider that the translation into Spanish has helped to improve pharmacotherapy in older patients with polypharmacy and multimorbidity in our linguistic environment.

Fatores Associados aos Triggers e Eventos Adversos em Pediatria / Factors Associated with Triggers and Adverse Events in Pediatrics

Introdução: A ocorrência frequente de eventos adversos durante a internação hospitalar demanda meios proativos de gerenciamento de riscos, incluindo a verificação de rastreadores/triggers. Objetivo: verificar os fatores associados aos triggers e eventos adversos na internação pediátrica. Material e Métodos: Pesquisa transversal embasada na metodologia do Institute for Healthcare Improvement (IHI), por meio da aplicação do Paediatric Trigger Tool (PTT) a uma amostra (n=194) de prontuários de pacientes pediátricos de um hospital do Centro-Oeste do Brasil. Foi realizada análise estatística descritiva, inferencial e regressão de Poisson. Resultados: Mais da metade (n=107; 55,15%) dos pacientes apresentou pelo menos um trigger na internação. Foram identificados 204 triggers/gatilhos, com maior ocorrência de queda de hemoglobina/hematócrito (9,80%), queda de saturação de oxigênio (9,80%) e aumento de marcadores de funções renais (9,20%). Do total de gatilhos, 64 (31,37%) eventos adversos foram confirmados, os quais foram classificados majoritariamente como dano temporário com necessidade de suporte ao paciente (65,62%). O tempo de internação (p-valor=0,004) e o caráter da internação (p-valor<0,001) foram variáveis associadas à ocorrência de triggers. Caráter de internação e admissões provenientes de outras instituições foram preditores na ocorrência de triggers e eventos adversos. Discussão: O estudo encontrou 31,37% dos triggers resultando em danos ao paciente, a detecção precoce é essencial na segurança do paciente pediátrico, internações prolongadas estão ligadas a infecções e eventos adversos, transferências de pacientes exigem medidas de segurança rigorosas e eficazes. Conclusões: internações prolongadas e crianças admitidas via transferência merecem atenção a triggers e/ou eventos adversos concretizados.

Introduction: The frequent occurrence of adverse events during hospital admission demands proactive means of risk management, including checking trackers/triggers. Objective: to verify the factors associated with triggers and adverse events in pediatric hospitalization. Material and Methods: Cross-sectional research based on the Institute for Healthcare Improvement (IHI) methodology, through the application of the Pediatric Trigger Tool (PTT) to a sample (n= 194) from medical records of pediatric patients from a hospital in the Center-West of Brazil. Descriptive, inferential statistical analysis and Poisson regression were performed. Results: More than half (n=107; 55.15%) of patients had at least one trigger upon admission. 204 triggers were identified, with the highest occurrence of a drop in hemoglobin/hematocrit (9.80%), a drop in oxygen saturation (9.80%) and an increase in kidney function markers (9.20%). Of the total triggers, 64 (31.37%) adverse events were confirmed, which were mostly classified as temporary damage requiring patient support (65.62%). The length of stay (p-value=0.004) and the nature of the hospitalization (p-value<0.001) were variables associated with the occurrence of triggers. Character of hospitalization and admissions from other institutions were predictors of the occurrence of triggers and adverse events. Discussion: The study found 31.37% of triggers resulting in harm to the patient, early detection is essential in pediatric patient safety, prolonged hospitalizations are linked to infections and adverse events, patient transfers require rigorous and effective safety measures. Conclusions: Prolonged hospitalizations and children admitted via transfer deserve attention to triggers and/or adverse events.

Introducción: La frecuente aparición de eventos adversos durante el ingreso hospitalario exige medios proactivos de gestión de riesgos, incluida la verificación de rastreadores/disparadores. Objetivo: verificar los factores asociados a desencadenantes y eventos adversos en la hospitalización pediátrica, Material y Métodos: Investigación transversal basada en la metodología Institute for Healthcare Improvement (IHI), mediante la aplicación del Pediatric Trigger Tool (PTT) a una muestra (n= 194) de historias clínicas de pacientes pediátricos de un hospital del Centro-Oeste de Brasil. Se realizaron análisis estadísticos descriptivos, inferenciales y regresión de Poisson. Resultados: Más de la mitad (n=107; 55,15%) de los pacientes presentaron al menos un desencadenante al ingreso. Se identificaron 204 desencadenantes, con mayor incidencia de descenso de la hemoglobina/hematocrito (9,80%), descenso de la saturación de oxígeno (9,80%) y aumento de los marcadores de función renal (9,20%). Del total de desencadenantes, se confirmaron 64 (31,37%) eventos adversos, los cuales en su mayoría fueron clasificados como daños temporales que requirieron apoyo del paciente (65,62%). La duración de la estancia (p-valor=0,004) y la naturaleza de la hospitalización (p-valor<0,001) fueron variables asociadas con la aparición de desencadenantes. El carácter de la hospitalización y los ingresos de otras instituciones fueron predictores de la aparición de desencadenantes y eventos adversos. Discusión: El estudio encontró que el 31,37% de los desencadenantes resultan en daño al paciente, la detección temprana es esencial en la seguridad del paciente pediátrico, las hospitalizaciones prolongadas están vinculadas a infecciones y eventos adversos, los traslados de pacientes requieren medidas de seguridad rigurosas y efectivas. Conclusiones: Las hospitalizaciones prolongadas y los niños ingresados ​​vía traslado merecen atención a los desencadenantes y/o eventos adversos.

Transferencia segura de pacientes y mejora de la comunicación en distintos entornos asistenciales / Safe handoff practices and improvement of communication in different paediatric settings

El manejo deficiente de información, en especial durante la transferencia o el traspaso de cuidados, contribuye en gran parte de los eventos adversos relacionados con la asistencia sanitaria. El Comité de Calidad Asistencial y Seguridad en el Paciente de la Asociación Española de Pediatría ha confeccionado este documento para ofrecer una aproximación a los procesos de transferencia en distintos ámbitos asistenciales pediátricos: urgencias-emergencias, hospitalización, cuidados intensivos, neonatología y atención primaria. Se describen recursos para lograr una comunicación segura y efectiva en todos estos ámbitos, empleando, entre otros métodos, herramientas estandarizadas de transferencia. Se proponen también recomendaciones para la prevención de errores de medicación durante los procesos de transferencia, la mejora de seguridad durante los traslados y derivaciones entre ámbitos, y también para un mejor traspaso de información asistencial en los niños y adolescentes con enfermedades crónicas y complejidad asistencial. (AU)

Inadequate information management, especially during patient handoff, contributes to a large part of health care-related adverse events. The Committee for Quality of Care and Patient Safety of the Asociación Española de Pediatría has developed this document to provide an overview of handover practices in different paediatric care settings (emergency, inpatient, intensive care, neonatal and primary care). It describes resources to achieve safe and effective communication in all these settings, such as standardized handoff tools. It also proposes recommendations for the prevention of medication errors during the handover process, to improve safety in interhospital and intrahospital patient transfer, and to optimize communication and continuity of care in chronically ill and medically complex children. (AU)

Safe handoff practices and improvement of communication in different paediatric settings.

Inadequate information management, especially during patient handoff, contributes to a large part of health care-related adverse events. The Committee for Quality of Care and Patient Safety of the Asociación Española de Pediatría has developed this document to provide an overview of handover practices in different paediatric care settings (emergency, inpatient, intensive care, neonatal and primary care). It describes resources to achieve safe and effective communication in all these settings, such as standardised handoff tools. It also proposes recommendations for the prevention of medication errors during the handover process, to improve safety in interhospital and intrahospital patient transfer, and to optimise communication and continuity of care in chronically ill and medically complex children.

Long-Term Safety Profile and Off-Label Use of JAK Inhibitors in Dermatological Disorders. / [Artículo traducido] Perfil de seguridad a largo plazo y usos fuera de indicación de los inhibidores de JAK en dermatología.

JAK inhibitors target specific inflammatory cytokines involved in various inflammatory diseases. Four molecules have been approved for dermatological use: upadacitinib, baricitinib, abrocitinib and topical ruxolitinib. Off-label prescriptions for other dermatological conditions have been reported. We conducted a narrative review of the literature to assess the long-term safety profile of currently approved JAK inhibitors in dermatology, and their off-label use in skin disorders. We performed literature searches with PubMed and Google Scholar from January 2000 to January 2023, using the keywords "Janus kinase inhibitors", "JAK inhibitors","off-label", "dermatology", "safety", "adverse events", "ruxolitinib", "upadacitinib","abrocitinib" and "baricitinib". Our search yielded a total of 37 dermatological disorders with studies supporting the use of these JAK inhibitors. Preliminary studies indicate that JAK inhibitors generally have a favorable safety profile and can be considered as an option in many dermatological disorders.