ABSTRACT OBJECTIVE To assess regional and national mortality and years of life lost (YLL) related to adverse drug events in Brazil. METHODS This is an ecological study in which death records from 2009 to 2018 from the Mortality Information System were analyzed. Codes from the International Classification of Diseases 10th revision (ICD-10) that indicated drugs as the cause of death were identified. The number of deaths and the YLL due to adverse drug events were obtained. Crude, age- and gender-specific, and age-adjusted mortality rates and YLL rates per 100,000 inhabitants were formed by year, age group, gender, and Brazilian Federative Unit. Rate ratios were calculated by comparing rates from 2009 to 2018. A joinpoint regression model was applied for temporal analysis. RESULTS For the selected ICD-10 codes, a total of 95,231 deaths and 2,843,413 YLL were recorded. Mortality rates from adverse drug events increased by a mean of 2.5% per year, and YLL rates increased by 3.7%. Increases in rates were observed in almost all age groups for both genders. Variations in rates were found between Federative Units, with the highest age-adjusted mortality and YLL rates occurring in the Distrito Federal. CONCLUSIONS The numbers and rates of deaths and YLL increased during the study period, and variations in rates of deaths and YLL were observed between Brazilian Federative Units. Information on multiple causes of death from death certificates can be useful for quantifying adverse drug events and analyzing them geographically, by age and by gender.

ABSTRACT OBJECTIVE To assess regional and national mortality and years of life lost (YLL) related to adverse drug events in Brazil. METHODS This is an ecological study in which death records from 2009 to 2018 from the Mortality Information System were analyzed. Codes from the International Classification of Diseases 10th revision (ICD-10) that indicated drugs as the cause of death were identified. The number of deaths and the YLL due to adverse drug events were obtained. Crude, age- and gender-specific, and age-adjusted mortality rates and YLL rates per 100,000 inhabitants were formed by year, age group, gender, and Brazilian Federative Unit. Rate ratios were calculated by comparing rates from 2009 to 2018. A joinpoint regression model was applied for temporal analysis. RESULTS For the selected ICD-10 codes, a total of 95,231 deaths and 2,843,413 YLL were recorded. Mortality rates from adverse drug events increased by a mean of 2.5% per year, and YLL rates increased by 3.7%. Increases in rates were observed in almost all age groups for both genders. Variations in rates were found between Federative Units, with the highest age-adjusted mortality and YLL rates occurring in the Distrito Federal. CONCLUSIONS The numbers and rates of deaths and YLL increased during the study period, and variations in rates of deaths and YLL were observed between Brazilian Federative Units. Information on multiple causes of death from death certificates can be useful for quantifying adverse drug events and analyzing them geographically, by age and by gender. (YLL Brazil 200 201 analyzed th ICD10 ICD 10 (ICD-10 identified obtained Crude genderspecific, genderspecific gender specific, specific gender-specific ageadjusted adjusted 100000 100 000 100,00 year group Unit analysis ICD-1 codes 95231 95 231 95,23 2843413 2 843 413 2,843,41 recorded 25 5 2.5 37 3 7 3.7% genders Units Federal period geographically 20 ICD1 1 (ICD-1 10000 00 100,0 ICD- 9523 9 23 95,2 284341 84 41 2,843,4 2. 3.7 (ICD- 1000 0 100, 952 95, 28434 8 4 2,843, 3. (ICD 2843 2,843 284 2,84 28 2,8 2,

ABSTRACT OBJECTIVE To describe the frequency and characteristics of hospitalizations for/with adverse drug events in the Brazilian unified health system routine data. METHODS Nationwide retrospective study using data obtained from a period of ten years from the Brazil Hospital Information System (SIH-SUS), an administrative database that registers hospitalizations in the unified health system. We selected hospitalizations with primary and/or secondary diagnosis related to adverse drug events according to a list of validated International Classification Disease 10th edition (ICD-10) codes. These events were described according to year, age group, sex, length of hospital stay, mortality, hospital costs, Brazilian geographical region, and category of ICD-10 codes. Crude hospitalization rates of adverse drug events per 100,000 inhabitants were obtained and Joinpoint Regression was used to analyze temporal changes in these rates along the years. The most frequent ICD-10 codes were also identified. RESULTS Over ten years, 603,663 hospitalizations in Brazil were found in the database, out of which 2.5% of the patients died. Though 2009 had the highest prevalence of hospitalization per 100,000 inhabitants (32.57), no significant annual change in rates was found for the entire period. All age groups and sexes presented a jointpoint in temporal series; however, only women had a significative increase trend. The most frequent codes were from the chapter of mental and behavioral disorders (F19.2, F19.0, and F19.5 codes). CONCLUSIONS The database methodology can be useful to estimate frequencies of adverse drug events and perform characterization nationwide and to help monitor morbidity along the years.

ABSTRACT OBJECTIVE To describe the frequency and characteristics of hospitalizations for/with adverse drug events in the Brazilian unified health system routine data. METHODS Nationwide retrospective study using data obtained from a period of ten years from the Brazil Hospital Information System (SIH-SUS), an administrative database that registers hospitalizations in the unified health system. We selected hospitalizations with primary and/or secondary diagnosis related to adverse drug events according to a list of validated International Classification Disease 10th edition (ICD-10) codes. These events were described according to year, age group, sex, length of hospital stay, mortality, hospital costs, Brazilian geographical region, and category of ICD-10 codes. Crude hospitalization rates of adverse drug events per 100,000 inhabitants were obtained and Joinpoint Regression was used to analyze temporal changes in these rates along the years. The most frequent ICD-10 codes were also identified. RESULTS Over ten years, 603,663 hospitalizations in Brazil were found in the database, out of which 2.5% of the patients died. Though 2009 had the highest prevalence of hospitalization per 100,000 inhabitants (32.57), no significant annual change in rates was found for the entire period. All age groups and sexes presented a jointpoint in temporal series; however, only women had a significative increase trend. The most frequent codes were from the chapter of mental and behavioral disorders (F19.2, F19.0, and F19.5 codes). CONCLUSIONS The database methodology can be useful to estimate frequencies of adverse drug events and perform characterization nationwide and to help monitor morbidity along the years.

Resumo Objetivo: Descrever a frequência e as características dos eventos adversos a medicamentos em pacientes pediátricos internados em um hospital universitário terciário brasileiro. Métodos: Foi realizado um estudo transversal por meio da análise retrospectiva e manual de prontuários de 240 internações pediátricas para identificar eventos adversos a medicamentos utilizando 17 rastreadores. Quando foram identificados rastreadores no prontuário, os analistas investigaram extensivamente o prontuário para decidir a respeito da existência de um evento. O consenso sobre a ocorrência do evento foi obtido em reunião com uma equipe de profissionais da saúde. Os eventos foram classificados por categoria de dano e os medicamentos foram classificados de acordo com a Classificação Anatômica Terapêutico-Química. Os pacientes que sofreram eventos adventos foram comparados aos que não apresentaram eventos adversos, com o teste qui-quadrado e o teste U de Mann-Whitney. Resultados: Verificou-se um total de 62 eventos adversos e 18,8% dos pacientes apresentaram ao menos evento. As taxas de eventos adversos foram de 25,83 por 100 internações, 20,27 por 1.000 pacientes/dia, 25,94 por 1.000 medicamentos e 2,12 por 1.000 doses de medicamentos. Todos os eventos encontrados foram classificados como dano temporário e os medicamentos cardiovasculares foram frequentemente associados aos eventos. Grupos de pacientes com e sem eventos apresentaram diferenças (p < 0,05) em relação ao tempo de internação, número e doses de medicamentos. Conclusão: O uso de rastreadores demonstrou sua utilidade no contexto pediátrico ao identificar danos. As taxas de eventos adversos foram maiores do que as taxas de estudos anteriores, porém a categoria de dano foi menor que em outros estudos. Este estudo possibilita a medição dos eventos adversos a fim de definir estratégias para minimizar ou reduzir os danos.

Abstract Objective: To describe the frequency and characteristics of adverse drug events in pediatric inpatients in a Brazilian tertiary teaching hospital. Methods: A cross-sectional study was conducted by retrospective and manual chart review of 240 pediatric admissions to identify adverse drug events using 17 triggers. When triggers were detected in the chart, reviewers investigated the chart in depth to decide whether an event occurred. Consensus about the occurrence of the event was obtained in meeting with a healthcare team. Events were classified by harm category and drugs were classified according to the Anatomical Therapeutic Chemical Classification. Patients who had suffered were compared to those who had not experienced events using the chi-squared test and the Mann-Whitney U test. Results: A total of 62 adverse events were found, and 18.8% of the patients had at least one event. Adverse events rates were 25.83 per 100 admissions, 20.27 per 1000 patient-days, 25.94 per 1000 drugs, and 2.12 per 1000 drug doses. All events found were classified as temporary harm, and cardiovascular drugs were most frequently related to events. Groups of patients with and without event were segregated (p < 0.05) by the length of stay, number of drugs, and drug doses. Conclusion: The use of triggers demonstrated its utility in a pediatric setting by identifying harm. Adverse events rates were found to be higher than those of previous studies, but the harm rate was lower than other studies. This study enables the measurement of adverse events in order to define strategies to mitigate or reduce harm.

RESUMO Objetivo: Descrever as intervenções farmacêuticas de um serviço farmacêutico clínico vertical, para a promoção do uso racional do omeprazol intravenoso. Métodos: Estudo prospectivo e descritivo realizado em um hospital universitário da região Centro-Oeste do Brasil, no período de novembro de 2014 a maio de 2015. O serviço consistia na análise da adequabilidade da via de administração do omeprazol em relação às condições clínicas do paciente, bem como a utilização do diluente adequado. As intervenções eram registradas em prontuário e, posteriormente, avaliadas quanto à aceitação. Resultados: Foram avaliadas 770 prescrições. As intervenções relacionadas à substituição do diluente foram mais aceitas (p<0,001), e os cirurgiões foram a especialidade que utilizou a via intravenosa de maneira inadequada (p<0,001). Conclusão: Embora parcialmente aceitas, as intervenções farmacêuticas puderam contribuir com a melhoria da segurança dos pacientes, uma vez que permitiram a utilização de uma via de administração mais segura.

ABSTRACT Objective: To describe the pharmaceutical interventions of a vertical clinical pharmacy service to promote the rational use of intravenous omeprazole. Methods: A prospective and descriptive study carried out at a university hospital in the Midwestern Region of Brazil, from November 2014 to May 2015. The service consisted of the analysis of adequacy of the route of administration of omeprazole in relation to the clinical conditions of the patient, as well as the use of the appropriate diluent. Interventions were recorded in medical records and subsequently evaluated for acceptance. Results: A total of 770 prescriptions were evaluated. Interventions related to diluent replacement were more accepted (p<0.001), and surgeons were the specialty that used the intravenous route inappropriately (p<0.001). Conclusion: Although partially accepted, pharmaceutical interventions could contribute to improve patient safety, since they allowed the use of a safer route of administration.

Resumo Objetivo: Descrever o processo de tradução, adaptação e validação para o português do Pediatric Trigger Toolkit: Measuring Adverse Drug Events in the Children's Hospital. Métodos: O processo de validação do instrumento de pesquisa foi realizado em 5 etapas: (I) tradução do inglês para o português por dois tradutores independentes; (II) síntese das versões traduzidas; (III) adaptação dos rastreadores para realidade brasileira por meio do método Delphi modificado, em duas rodadas; (IV) aplicação do instrumento de pesquisa na revisão de 240 internações de 2014; e (V) retrotradução do português para o inglês. Resultados: A etapa de tradução resultou em duas versões traduzidas, que foram sintetizadas de forma a obter equivalência ao contexto cultural brasileiro. O processo de adaptação do instrumento de pesquisa possibilitou a inclusão e adaptação dos rastreadores, bem como a exclusão de rastreadores segundo consenso obtido entre os especialistas na etapa Delphi. O valor preditivo positivo do instrumento de pesquisa foi de 13,51% e o rastreador anti-histamínico foi o que apresentou maior valor preditivo positivo. Conclusão: O instrumento de pesquisa pode ser utilizado para rastrear a ocorrência de eventos adversos a medicamentos em pacientes pediátricos nos hospitais brasileiros. Apesar das adaptações realizadas, rastreadores que não foram identificados ou com baixo valor preditivo positivo podem indicar, ainda, a necessidade de modificações. Entretanto, mais estudos são necessários antes de modificar ou excluir algum rastreador.

Abstract Objective: To describe the process of translation, adaptation, and validation of the Brazilian Portuguese version of the Pediatric Trigger Toolkit: Measuring Adverse Drug Events in the Children's Hospital. Methods: The validation process for the research instrument was carried out in five steps: (I) translation from English into Brazilian Portuguese by two independent translators; (II) synthesis of the translated versions; (III) adaptation of the triggers to the Brazilian context using a modified Delphi method carried out in two rounds; (IV) application of the research instrument in the review of 240 hospitalizations during 2014; and (V) back-translation from Brazilian Portuguese to English. Results: The translation step resulted in two versions, which were then synthesized to obtain equivalence within the Brazilian cultural context. The process of adapting the research instrument allowed the inclusion and adaptation of some triggers, as well as the exclusion of others, based on the consensus reached among experts during the Delphi step. The positive predictive value of the research instrument was 13.51%, and the antihistamine trigger presented the highest positive predictive value. Conclusion: The research instrument can be used to track the occurrence of adverse drug events in pediatric patients in Brazilian hospitals. Despite the adjustments made, triggers that were not identified or that had low positive predictive value can suggest the need for additional changes. However, more studies are needed before modifying or removing a trigger.

RESUMO Introdução As reações adversas a medicamentos são objeto de estudo da farmacovigilância, ciência que utiliza, sobretudo, as notificações espontâneas feitas por profissionais de saúde. Há dificuldade de reconhecimento dos profissionais quanto a sua importância na segurança do paciente. As causas da subnotificação são atribuídas a falta de conhecimentos, percepção e compreensão dos incidentes. Objetivo Identificar o conhecimento e as condutas dos profissionais de saúde de um hospital de ensino em relação às reações adversas a medicamentos e à farmacovigilância e se há associação com o seu perfil profissiográfico. Métodos Estudo transversal, utilizando-se um instrumento validado que aborda questões sobre caracterização da população estudada, conhecimentos e condutas. Resultados Os médicos demonstraram maior conhecimento sobre reações adversas a medicamentos, e os técnicos em enfermagem, menor. No entanto, o entendimento sobre farmacovigilância foi maior entre os farmacêuticos. O tempo de formação e atuação na instituição está associado ao conhecimento sobre as reações adversas a medicamentos Conclusão: Os resultados deste estudo evidenciaram que a formação do profissional influencia seu conhecimento e condutas frente às reações adversas a medicamentos.

ABSTRACT Introduction Adverse Drug Reactions are studied by the science of pharmacovigilance, which makes particular use of spontaneous reports made by health professionals, although such professionals experience difficulties in recognizing adverse reactions and their importance in patient safety. The causes of underreporting are attributed to a lack of knowledge, awareness and understanding of incidents. Objective Methods: A cross-sectional study was conducted using a validated instrument in order to characterize the population under study, determining its knowledge and behaviors Results: Doctors demonstrated a greater knowledge of adverse drug reactions than nursing technicians; however an understanding of pharmacovigilance was higher among pharmacists. The length of time spent in training and working in an institution were also associated with a knowledge of adverse drug reactions Conclusion The results of this study show that professional training influences knowledge and behaviors on adverse drug reactions.

The objective of this study was to analyze the use of medications administered though tubes to inpatients of the adult and neonatal intensive care units of a teaching hospital. This descriptive, exploratory, quantitative study was performed in March of 2011 based on prescriptions from the respective units, focused on the recommendations of the use of those medications through a tube. Information was collected and analyzed using Epi Info 3.5.2. A total of 572 prescriptions were analyzed, adding up to 5,283 medications. Among oral medications, most (88.8%) were prescribed to be administered through a tube; and 11 were of restricted use. The high frequency of prescriptions for medications administered through tubes, associated with the different types of restrictions that make their use by this mean unfeasible, gives evidence of the need to implement continuing education programs, and to create educational handbooks seeking to improve the knowledge of the professionals involved.

Se objetivó analizar la utilización de medicamentos administrados por sonda a pacientes de unidades de terapia intensiva adulta y neonatal de un hospital de enseñanza. Estudio descriptivo, exploratorio, cuantitativo; realizado en marzo de 2011 partiendo de prescripciones originadas en dichas unidades, haciendo foco en las recomendaciones de uso de tales medicamentos vía sonda. La información fue recolectada y analizada en el programa EpiInfo 3.5.2. Se analizaron 572 prescripciones, incluyendo 5.283 medicamentos. Entre los medicamentos de forma farmacéutica para uso oral, la mayoría (88,8%) fue prescripta para administración por sonda. De ellos, 11 tenían restricciones para uso por esta vía. La gran cantidad de medicamentos prescriptos para administración por sonda aliada a las diferentes restricciones que desaconsejan su utilización por tal vía, expresan la necesidad de implantar programas de capacitación continua y la creación de manuales educativos que apunten a mejorar los conocimientos de los profesionales involucrados.

Este trabalho teve como objetivo analisar o uso de medicamentos administrados por sonda aos pacientes das unidades de terapia intensiva adulto e neonatal de um hospital de ensino. Trata-se de um estudo de caráter descritivo, exploratório e quantitativo, realizado em março/2011 a partir de prescrições oriundas das respectivas unidades, com foco nas recomendações de uso desses medicamentos via sonda. As informações foram coletadas e analisadas no programa Epi Info versão 3.5.2. Analisou-se 572 prescrições, somando 5.283 medicamentos. Dentre os medicamentos com forma farmacêutica de uso oral, a maioria (88,8%) foi prescrita para administração por sonda. Desta, 11 tiveram restrição de uso. A alta frequência de medicamentos prescritos para administração por sonda, aliada aos diferentes tipos de restrições que inviabilizam seu uso por essa via, evidencia a necessidade da implantação de programas de educação continuada, bem como a criação de manuais educativos que busquem aprimorar o conhecimento dos profissionais envolvidos.