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 Analisar o perfil farmacoterapêutico dos idosos atendidos em um Centro de Referência em Atenção à Saúde da Pessoa Idosa quanto ao uso de medicamentos potencialmente inapropriados (MPI) por meio de três critérios de rastreamento e determinar fatores associados à prescrição de MPI. Método Estudo transversal com dados obtidos por revisão retrospectiva dos prontuários de idosos, atendidos entre 2017 e 2018 por médico geriatra. Para identificar os MPI, utilizaram-se os Critérios de Beers, o Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions (STOPP) e o Consenso Brasileiro de Medicamentos Potencialmente Inapropriados para Idosos. Características relacionadas ao perfil sociodemográfico (idade e sexo), de hábitos de vida (tabagismo e consumo de álcool), clínico (doenças) e farmacoterapêutico (medicamentos e Índice de Complexidade da Farmacoterapia - ICFT) foram avaliadas. Resultados Foram analisados 406 prontuários e identificados 3.059 medicamentos prescritos, dos quais 32,1% são MPI segundo Critérios STOPP, 14,4% pelo Consenso Brasileiro e 11,7% pelos Critérios de Beers. No total, 81,1% dos idosos apresentaram ao menos um MPI. Regressão de Poisson demonstrou associação entre a prescrição de MPI com polifarmácia, maior número de sinais e sintomas e maior valor de ICFT em ao menos um dos critérios. A força de concordância entre os critérios de MPI foi moderada. Conclusões A maioria dos prontuários analisados possuíam ao menos um MPI prescrito, sendo que os Critérios STOPP identificaram uma maior quantidade de MPI. Estratégias devem ser implementadas para melhorar a farmacoterapia dos idosos com atenção para os que apresentam fatores associados a MPI em seu perfil.

Abstract Objective To analyze the pharmacotherapeutic profile of the old people assisted at a Reference Center in Health Care for Old People regarding the use of potentially inappropriate medications (PIM) using three screening criteria and to determine factors associated with the prescription of PIM. Method Cross-sectional study with data obtained by retrospective review of the medical records of the old people, attended between 2017 and 2018 by a geriatric doctor. To identify the PIM, the Beers Criteria, the Screening Tool of Older Persons’ Potentially Inappropriate Prescriptions (STOPP) and the Brazilian Consensus on Potentially Inappropriate Medications for Old People were used. Characteristics related to the sociodemographic profile (age and sex), lifestyle (smoking and alcohol consumption), clinical (diseases) and pharmacotherapeutic (medications and Medication Regimen Complexity Index - MRCI) were evaluated. Results 406 medical records were analyzed and 3,059 prescription medications were identified, of which 32.1% are PIM according to STOPP Criteria, 14.4% by the Brazilian Consensus and 11.7% by the Beers Criteria. In total, 81.1% of the old people had at least one PIM. Poisson regression demonstrated an association between the prescription of PIM with polypharmacy, a greater number of signs and symptoms and a higher MRCI value in at least one of the criteria. The strength of agreement between the PIM criteria was moderate. Conclusions Most of the analyzed medical records had at least one prescribed PIM, and the STOPP Criteria identified a greater amount of PIM. Strategies must be implemented to improve the pharmacotherapy of old people with attention to those who have factors associated with PIM in their profile.

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.