[Deaths from adverse drug events in Brazil: Mortality Information System as a source of information]. / Óbitos por eventos adversos a medicamentos no Brasil: Sistema de Informação sobre Mortalidade como fonte de informação.

Adverse drug events (ADEs) are harmful events caused by medication, and some of which can lead to death. Death records are an important source of information when using codes from the 10th revision of the International Classification of Diseases (ICD-10) suggestive of ADE. This study aimed to identify the ADEs registered in Brazililian Mortality Information System (SIM), analyzing data distribution by year, age group, and type of event. This is an ecological study with retrospective data collection, identifying ADEs in the SIM, using the ICD-10 codes. The study included deaths that occurred in Brazil from 2008 to 2016. An increase in the number of deaths associated with ADE was observed from 2008 to 2016, with a mortality rate per 1 million inhabitants ranging from 8.70 to 14.40 in the period. Most events corresponded to mental and behavioral disorders due to the use of psychotropic drugs. Most deaths (12,311) related to ADE codes were identified in several chapters of the ICD-10. Chapter XX, about adverse events, allowed the identification of a smaller number of deaths (4,893). Higher event rates were observed among individuals aged 60 years and over (39.8/1 million) and children younger than one year (22.0/1 million). The identification of ADE-related deaths on the SIM is an important strategy for addressing undesirable drug-related events. Deaths related to the use of psychotropic drugs were the most frequent ADE-related deaths and the elderly were the age group most affected by ADEs.

Os eventos adversos a medicamentos (EAM) são danos aos pacientes relacionados ao uso de medicamentos, parte dos quais pode levar à morte. Os registros de óbitos são fonte importante de informação, quando se empregam os códigos da 10ª revisão da Classificação Internacional de Doenças (CID-10) sugestivos de EAM. O estudo identificou os EAM registrados no Sistema de Informação sobre Mortalidade (SIM), analisando sua distribuição por ano, faixa etária e tipo de evento. Trata-se de um estudo ecológico com coleta de dados retrospectiva de identificação de EAM no SIM, por meio dos códigos da CID-10. O estudo compreendeu óbitos ocorridos no Brasil, de 2008 a 2016. Houve aumento nas proporções de óbitos associados aos EAM de 2008 a 2016, com taxa de mortalidade por 1 milhão de habitantes indo de 8,70 para 14,40 no período. A maioria dos eventos correspondeu aos transtornos mentais e comportamentais em razão do uso de psicofármacos. A maioria dos óbitos (12.311) relacionados a códigos de EAM foram identificados em diversos capítulos da CID-10. Já o capítulo XX, específico para eventos adversos, permitiu identificar parcela menor de óbitos (4.893). As maiores taxas de eventos ocorreram entre indivíduos com 60 anos ou mais (39,8/1 milhão) e crianças menores de um ano (22,0/1 milhão). A identificação de óbitos associados aos EAM, por meio do SIM, constitui uma estratégia importante para a abordagem dos eventos indesejáveis relacionados aos medicamentos. Os óbitos relacionados ao uso de psicofármacos foram os de maior frequência e os idosos foram a faixa etária mais acometida por EAM.

Los eventos adversos a los medicamentos (EAM) son daños a los pacientes relacionados con el uso de medicamentos, algunos de los cuales pueden provocar la muerte. Los registros de defunciones son fuente importante de información, cuando se emplean los códigos de la 10ª revisión de la Clasificación Internacional de Enfermedades (CIE-10) sugestivos de EAM. Identificar los EAM registrados en el Sistema de Información sobre Mortalidad (SIM), analizando su distribución, por año, grupo de edad y tipo de evento. Estudio ecológico con recolección de datos retrospectiva, de identificación de EAM en el SIM, por medio de los códigos de la CIE-10. El estudio comprendió muertes ocurridas en Brasil, de 2008 a 2016. Hubo aumento en las proporciones de muertes asociadas a la EAM de 2008 a 2016, con la tasa de mortalidad por 1 millón de habitantes pasando de 8,70 para 14,40, en el período. La mayoría de los eventos correspondieron a los trastornos mentales y del comportamiento debidos al consumo de psicofármaco. La mayoría de las muertes (12.311) relacionadas con los códigos EAM se identificaron en varios capítulos de la CIE-10. El capítulo XX, sobre eventos adversos, identificó un número menor de muertes (4.893). Las tasas más altas de eventos ocurrieron entre personas de 60 años o más (39.8/1 millón) y niños menores de un año (22.0/1 millón). La identificación de muertes asociadas a los EAM, por medio del SIM, constituye una estrategia importante para el enfoque de los eventos indeseables relacionados con los medicamentos. Las muertes relacionadas con el uso de psicofármacos fueron las más frecuentes y los ancianos fueron el grupo de edad más afectado por EAM.

Identifying adverse drug events in patients at a pediatric ward in a Brazilian hospital: application and performance of the triggers / Identificação de eventos adversos a medicamentos em pacientes de enfermaria pediátrica em um hospital brasileiro: aplicação e desempenho de rastreadores

Abstract Objectives: to evaluate the performance of a trigger tool in identifying adverse drug events (ADE) in hospitalized children. Methods: a retrospective cohort study review on 133 medical records at a federal maternal and child reference hospital in Rio de Janeiro in 2016. A list of 14 triggers was developed to detect ADE in the pediatric population. Three steps were performed: (1) search for triggers; (2) selection of suspected cases of ADE and (3) final determination of ADE by experts' consensus. Results: 360 triggers were identified in 100 hospitalizations (75.2%), with an average of 2.7 triggers/ hospitalization. The most frequent triggers were "abrupt medication stop" (79.7%); "antiemetics use" (8.9%) and "laxatives use" (7.2%); while the "diphenhydramine use", "phytomenadione use" and "excessive sedation/lethargy/fall/hypotension" obtained the highest performance indicating ADE every time they occurred. Thirty-one ADE were identified in 12.8% of the hospitalizations; 11 (35.5%) ADE were detected without the aid of the triggers thus, pruritus and diarrhea were the most frequent. Conclusion: the trigger tool proved to be useful in identifying ADE in hospitalized children, especially if high performance and high frequency triggers are used in identifying the events. The inclusion of the triggers "diarrhea" and "pruritus", may favor the identification of ADE in patients at pediatric wards.

Resumo Objetivos: avaliar o desempenho de uma ferramenta de rastreamento de eventos adversos a medicamentos (EAM) em crianças hospitalizadas. Métodos: estudo de coorte retrospectivo com revisão de 133 prontuários de hospital federal de referência materno infantil no Rio de Janeiro, em 2016. Uma lista de 14 rastreadores foi usada para detecção de EAM na população pediátrica. Foram realizadas 3 etapas: (1) busca de rastreadores; (2) seleção dos casos suspeitos de EAM e (3) determinação final do EAM por consenso entre especialistas. Resultados: foram identificados 360 rastreadores em 100 internações (75,2%), com média de 2,7 rastreadores/internação. Os rastreadores mais frequentes foram "interrupção abrupta da medicação" (79,7%); "uso de antieméticos" (8,9%) e "uso de laxantes" (7,2%) enquanto que "uso de difenidramina", "uso de fitomenadiona" e "excesso de sedação/letargia/queda/hipotensão" obtiveram o maior rendimento indicando EAM em todas as vezes que ocorreram. Trinta e um EAM foram identificados em 12,8% das internações; 11(35,5%) EAM foram detectados sem auxílio dos rastreadores, sendo prurido e diarreia os mais frequentes. Conclusão: a ferramenta de rastreadores mostrou-se útil para a identificação de EAM em crianças hospitalizadas, principalmente se forem utilizados rastreadores com alto rendimento e alta frequência na identificação de eventos. A inclusão dos rastreadores diarreia e prurido pode favorecer a identificação de EAM em pacientes de enfermaria pediátrica.

Predictors of adverse drug reactions associated with ribavirin in direct-acting antiviral therapies for chronic hepatitis C.

PURPOSE: To identify factors associated with the development of adverse drug reactions (ADR) in ribavirin therapeutic regimens. METHODS: A multicenter, prospective study was conducted in three public health hospitals in Rio de Janeiro between November 2015 and March 2018. Inclusion criteria were defined by patient follow-up at pharmaceutical consultation at the time of drug dispensing as those who used sofosbuvir in combination with simeprevir, daclatasvir, and/or ribavirin. All patients were invited to participate in the study during the first interview. Adverse drug reactions were reported according to the treatment regimen and frequency of occurrence. Statistical analysis was used to compare adverse reactions between treatments and their associated factors. RESULTS: A total of 405 patients were included in the study (mean age 59.6 ± 9.6 years); 61.0% were female, 88.1% were infected with genotype 1, and 65.4% were cirrhotic. The most prescribed treatment was the combination of sofosbuvir, daclatasvir, and ribavirin (55.3%). The majority of patients reported at least one ADR during treatment (83.2%), of which fatigue, anemia, and headache were the most common. Being female (OR = 1.86, [1.08-3.20]) and use of ribavirin (OR: 2.39; 95% CI [1.38-4.13]) were predictors for the development of ADR, which was also associated with development of anemia (OR: 10.28; 95% CI: [5.78-18.30]). Treatment efficacy was 98.1%. CONCLUSIONS: Direct-acting antiviral has been shown to be safe and effective. Therefore, use of ribavirin is questionable due to associated adverse reactions and similar efficacy to other treatments.

Interações medicamentosas potenciais em adultos e idosos na atenção primária / Potential drug interactions in adults and the elderly in primary health care

Resumo O objetivo do presente estudo foi caracterizar as interações medicamentosas potenciais (IMP) e avaliar os fatores associados à sua ocorrência em adultos e idosos assistidos pelo Programa Médico de Família de Niterói, Rio de Janeiro. Trata-se de um subestudo do ESTUDO DIGITALIS, que incluiu indivíduos cadastrados no Programa Médico de Família de Niterói (45-99 anos). Foram analisados 341 indivíduos com prescrição de dois ou mais medicamentos. A classificação das IMP seguiu o MICROMEDEX®. Houve 113 interações diferentes. Do total de indivíduos, 63,6% apresentaram pelo menos uma IMP. As variáveis com maior chance de IMP foram: menor escolaridade; renda inferior a R$800,00; ausência de plano de saúde; diagnóstico de hipertensão, diabetes, infarto agudo do miocárdio; e uso de 5 ou mais medicamentos prescritos. Após ajuste, as variáveis diagnóstico anterior de hipertensão e diabetes e uso de 5 ou mais medicamentos prescritos permaneceram significativas estatisticamente. É importante uma gestão cautelosa do tratamento na atenção básica com monitoramento das IMP, especialmente em pacientes mais susceptíveis.

Abstract The objective of the present study was to characterize the potential drug interactions (PDI), estimating the factors associated to their occurrence in adults and the elderly assisted by the Programa Médico de Família de Niterói, Rio de Janeiro. This is a sub-study of STUDY DIGITALIS, which included individuals enrolled in the Niteroi Family Medical Program (45-99 years). In this study, 341 individuals with a prescription of two or more drugs were analyzed. The classification of PDI followed MICROMEDEX. There were 113 different interactions. Of the total number of individuals, 63.6% had at least one PDI. The variables with higher probability of PDI were: lower level of schooling; income less than R$800.00; absence of health plan; previous diagnosis of hypertension and diabetes; use of 5 or more medications prescribed. After adjustment, the variables previous diagnosis of hypertension and diabetes and use of 5 or more prescription drugs remained statistically significant. Careful management of primary care treatment with monitoring is important in patients with PDI, especially in patients who are more susceptible.

[Potential drug interactions in adults and the elderly in primary health care]. / Interações medicamentosas potenciais em adultos e idosos na atenção primária.

The objective of the present study was to characterize the potential drug interactions (PDI), estimating the factors associated to their occurrence in adults and the elderly assisted by the Programa Médico de Família de Niterói, Rio de Janeiro. This is a sub-study of STUDY DIGITALIS, which included individuals enrolled in the Niteroi Family Medical Program (45-99 years). In this study, 341 individuals with a prescription of two or more drugs were analyzed. The classification of PDI followed MICROMEDEX. There were 113 different interactions. Of the total number of individuals, 63.6% had at least one PDI. The variables with higher probability of PDI were: lower level of schooling; income less than R$800.00; absence of health plan; previous diagnosis of hypertension and diabetes; use of 5 or more medications prescribed. After adjustment, the variables previous diagnosis of hypertension and diabetes and use of 5 or more prescription drugs remained statistically significant. Careful management of primary care treatment with monitoring is important in patients with PDI, especially in patients who are more susceptible.

O objetivo do presente estudo foi caracterizar as interações medicamentosas potenciais (IMP) e avaliar os fatores associados à sua ocorrência em adultos e idosos assistidos pelo Programa Médico de Família de Niterói, Rio de Janeiro. Trata-se de um subestudo do ESTUDO DIGITALIS, que incluiu indivíduos cadastrados no Programa Médico de Família de Niterói (45-99 anos). Foram analisados 341 indivíduos com prescrição de dois ou mais medicamentos. A classificação das IMP seguiu o MICROMEDEX®. Houve 113 interações diferentes. Do total de indivíduos, 63,6% apresentaram pelo menos uma IMP. As variáveis com maior chance de IMP foram: menor escolaridade; renda inferior a R$800,00; ausência de plano de saúde; diagnóstico de hipertensão, diabetes, infarto agudo do miocárdio; e uso de 5 ou mais medicamentos prescritos. Após ajuste, as variáveis diagnóstico anterior de hipertensão e diabetes e uso de 5 ou mais medicamentos prescritos permaneceram significativas estatisticamente. É importante uma gestão cautelosa do tratamento na atenção básica com monitoramento das IMP, especialmente em pacientes mais susceptíveis.

Consumption of the benzodiazepine clonazepam (Rivotril®) in Rio de Janeiro State, Brazil, 2009-2013: an ecological study. / Consumo do benzodiazepínico clonazepam (Rivotril®) no estado do Rio de Janeiro, Brasil, 2009-2013: estudo ecológico.

This descriptive, ecological study of clonazepam consumption in Rio de Janeiro State (RJ) estimated use prevalence from 2009 to 2013 using data from the National Controlled Product Management System operated by Brazil's health surveillance agency, Anvisa. Consumption was measured by total population and by population over 18 years old, using the standardised Daily Defined Doses of 8 mg (anticonvulsant) and 1 mg (sedative-hypnotic). The municipalities of the Rio de Janeiro Metropolitan Region were grouped by Human Development Index (HDI) and GINI index, subjected to cluster analysis and ranked by clonazepam consumption. From 2009 to 2013, consumption in the state rose from 0.35 to 1.97 DDD/1000 population, but the figures are higher for individuals over 18 years of age. A DDD of 1 mg instead of 8mg returns consumption in 2013 of 21 DDD/1000 population over 18 years of age. Consumption in 2013 was highest - 3.38 and 4.52 DDD, respectively - in Rio de Janeiro and Niterói, which have the highest HDIs. This suggests that up to 2% of the adult population uses clonazepam, possibly as a sedative-hypnotic. This broad use and use outside therapeutic indications deserves attention, given clonazepam's potential for abuse and adverse reactions.

O objetivo do estudo é estimar a prevalência do uso de clonazepam no Estado do Rio de Janeiro (RJ). Estudo ecológico e descritivo do consumo de clonazepam (2009-2013), com dados do Sistema Nacional de Gerenciamento de Produtos Controlados da Anvisa. O consumo foi medido pela Dose Diária Definida, com indicadores por população total e com 18 anos e mais utilizando a DDD padronizada de 8mg (anticonvulsivante) e a de 1mg (hipnosedativo). Os Municípios da Região Metropolitana foram agrupados segundo os Índices de Desenvolvimento Humano (IDH) e de GINI, submetidos à análise de conglomerados e apresentados segundo o consumo de clonazepam. No Estado do RJ, o consumo entre 2009 e 2013 aumentou de 0,35 para 1,97 DDD/1000 habitantes. Os valores são maiores para os indivíduos acima de 18 anos. Empregando-se 1mg ao invés de 8mg, chega-se a 21 DDD/1000 habitantes acima de 18 anos, em 2013. Rio de Janeiro e Niterói, com os maiores IDH, apresentaram em 2013 os maiores consumos, 3,38 e 4,52 DDD, respectivamente. Os dados sugerem que até 2% da população adulta é usuária de clonazepam, possivelmente como hipnosedativo. Deve-se atentar para o uso ampliado e fora de indicações terapêuticas, dados o potencial de abuso e as reações adversas ao clonazepam.

Consumo do benzodiazepínico clonazepam (Rivotril®) no estado do Rio de Janeiro, Brasil, 2009-2013: estudo ecológico / Consumption of the benzodiazepine clonazepam (Rivotril®) in Rio de Janeiro State, Brazil, 2009-2013: an ecological study

Resumo O objetivo do estudo é estimar a prevalência do uso de clonazepam no Estado do Rio de Janeiro (RJ). Estudo ecológico e descritivo do consumo de clonazepam (2009-2013), com dados do Sistema Nacional de Gerenciamento de Produtos Controlados da Anvisa. O consumo foi medido pela Dose Diária Definida, com indicadores por população total e com 18 anos e mais utilizando a DDD padronizada de 8mg (anticonvulsivante) e a de 1mg (hipnosedativo). Os Municípios da Região Metropolitana foram agrupados segundo os Índices de Desenvolvimento Humano (IDH) e de GINI, submetidos à análise de conglomerados e apresentados segundo o consumo de clonazepam. No Estado do RJ, o consumo entre 2009 e 2013 aumentou de 0,35 para 1,97 DDD/1000 habitantes. Os valores são maiores para os indivíduos acima de 18 anos. Empregando-se 1mg ao invés de 8mg, chega-se a 21 DDD/1000 habitantes acima de 18 anos, em 2013. Rio de Janeiro e Niterói, com os maiores IDH, apresentaram em 2013 os maiores consumos, 3,38 e 4,52 DDD, respectivamente. Os dados sugerem que até 2% da população adulta é usuária de clonazepam, possivelmente como hipnosedativo. Deve-se atentar para o uso ampliado e fora de indicações terapêuticas, dados o potencial de abuso e as reações adversas ao clonazepam.

Abstract This descriptive, ecological study of clonazepam consumption in Rio de Janeiro State (RJ) estimated use prevalence from 2009 to 2013 using data from the National Controlled Product Management System operated by Brazil's health surveillance agency, Anvisa. Consumption was measured by total population and by population over 18 years old, using the standardised Daily Defined Doses of 8 mg (anticonvulsant) and 1 mg (sedative-hypnotic). The municipalities of the Rio de Janeiro Metropolitan Region were grouped by Human Development Index (HDI) and GINI index, subjected to cluster analysis and ranked by clonazepam consumption. From 2009 to 2013, consumption in the state rose from 0.35 to 1.97 DDD/1000 population, but the figures are higher for individuals over 18 years of age. A DDD of 1 mg instead of 8mg returns consumption in 2013 of 21 DDD/1000 population over 18 years of age. Consumption in 2013 was highest - 3.38 and 4.52 DDD, respectively - in Rio de Janeiro and Niterói, which have the highest HDIs. This suggests that up to 2% of the adult population uses clonazepam, possibly as a sedative-hypnotic. This broad use and use outside therapeutic indications deserves attention, given clonazepam's potential for abuse and adverse reactions.

Adverse drug events identified in hospitalized patients in Brazil by International Classification of Diseases (ICD-10) code listings.

Studies of adverse drug events (ADEs) are important in order not to jeopardize the positive impact of pharmacotherapy. These events have substantial impact on the population morbidity profiles, and increasing health system operating costs. Administrative databases are an important source of information for public health purposes and for identifying ADEs. In order to contribute to learning about ADE in hospitalized patients, this study examined the potential of applying ICD-10 (10th revision of the International Classification of Diseases) codes to a national database of the public health care system (SIH-SUS). The study comprised retrospective assessment of ADEs in the SIH-SUS administrative database, from 2008 to 2012. For this, a list of ICD-10 codes relating to ADEs was built. This list was built up by examining lists drawn up by other authors identified by bibliographic search in the MEDLINE and LILACS and consultations with experts. In Brazil, 55,604,537 hospital admissions were recorded in the SIH-SUS, between 2008 and 2012, of which 273,440 (0.49%) were related to at least one ADE. The proportions and rates seem to hold constant over the study period. Fourteen out of 20 most frequent ADEs were identified in codes relating to mental disorders. Intoxications figure as the second most frequently recorded group of ADEs in the SIH-SUS, comprising 76,866 hospitalizations. Monitoring of ADEs in administrative databases using ICD-10 codes is feasible, even in countries with information systems under construction, and can be an innovative tool to complement drug surveillance strategies in place in Brazil, as well as in others countries.

Adverse drug events identified in hospitalized patients in Brazil by International Classification of Diseases (ICD-10) code listings / Eventos adversos a medicamentos identificados em pacientes hospitalizados no Brasil de acordo com códigos da Classificação Internacional de Doenças (CID-10) / Eventos Adversos por Medicamentos identificados en pacientes hospitalizados en Brasil según los listados de códigos de la Clasificación Internacional de Enfermedades (CIE-10)

Studies of adverse drug events (ADEs) are important in order not to jeopardize the positive impact of pharmacotherapy. These events have substantial impact on the population morbidity profiles, and increasing health system operating costs. Administrative databases are an important source of information for public health purposes and for identifying ADEs. In order to contribute to learning about ADE in hospitalized patients, this study examined the potential of applying ICD-10 (10th revision of the International Classification of Diseases) codes to a national database of the public health care system (SIH-SUS). The study comprised retrospective assessment of ADEs in the SIH-SUS administrative database, from 2008 to 2012. For this, a list of ICD-10 codes relating to ADEs was built. This list was built up by examining lists drawn up by other authors identified by bibliographic search in the MEDLINE and LILACS and consultations with experts. In Brazil, 55,604,537 hospital admissions were recorded in the SIH-SUS, between 2008 and 2012, of which 273,440 (0.49%) were related to at least one ADE. The proportions and rates seem to hold constant over the study period. Fourteen out of 20 most frequent ADEs were identified in codes relating to mental disorders. Intoxications figure as the second most frequently recorded group of ADEs in the SIH-SUS, comprising 76,866 hospitalizations. Monitoring of ADEs in administrative databases using ICD-10 codes is feasible, even in countries with information systems under construction, and can be an innovative tool to complement drug surveillance strategies in place in Brazil, as well as in others countries.

Os estudos sobre eventos adversos a medicamentos (EAMs) são importantes para evitar de prejudicar o efeito positivo da farmacoterapia. Os EAMs têm impacto substancial nos perfis de morbidade da população e no aumento dos custos operacionais do sistema de saúde. As bases de dados administrativos representam uma fonte de informação importante para fins de saúde pública em geral e especificamente para identificar os EAMs. No intuito de contribuir para o conhecimento sobre EAMs em pacientes hospitalizados, o estudo examinou a aplicabilidade dos códigos da CID-10 (10ª revisão da Classificação Internacional de Doenças) ao Sistema de Informações Hospitalares do Sistema Único de Saúde (SIH-SUS). O estudo integrou uma avaliação retrospectiva de dados administrativos do SIH-SUS referentes aos anos de 2008 a 2012. Para tanto, foi elaborada uma lista de códigos da CID-10 relacionados a EAMs. A lista foi produzida a partir de uma consulta às listas projetadas por outros autores e identificadas através de uma busca em MEDLINE e LILACS e consultas com especialistas. No Brasil, foram registradas 55.604.537 internações hospitalares no SIH-SUS entre 2008 e 2012, das quais 273.440 (0,49%) estiveram relacionadas a pelo menos um EAM. As proporções e taxas de EAMs permaneceram constantes ao longo do período estudado. Quatorze dos vinte EAMs mais frequentes foram identificados através de códigos relacionados a transtornos psiquiátricos. As intoxicações figuram como o segundo grupo mais frequente de EAMs registrados no SIH-SUS, com 76.866 internações. O monitoramento dos EAMs com o uso dos códigos da CID-10 mostrou ser uma metodologia viável, mesmo em países com sistemas de informação ainda incompletos, e pode ser uma ferramenta inovadora para complementar as estratégias atuais de vigilância farmacológica no Brasil, assim como, em outros países.

Los estudios sobre eventos adversos por medicamentos (EAMs) son importantes, para no comprometer el impacto positivo de la farmacoterapia. Estos eventos tienen un impacto sustancial en los perfiles de morbilidad de la población e incrementan los costes operativos del sistema de salud. Las bases de datos administrativas son una importante fuente de información por motivos de salud pública y para identificar EAMs. Con el fin de contribuir al aprendizaje sobre EAM en pacientes hospitalizados, este estudio examinó el potencial de aplicar códigos CIE-10 (10ª revisión de la Clasificación Internacional de Enfermedades) a una base datos nacional del sistema de salud público (SIH-SUS). Este estudio estuvo constituido por una evaluación retrospectiva de EAMs, en la base de datos administrativa del SIH-SUS, desde 2008 a 2012. Para ello, se desarrolló la lista de la CIE-10 con códigos para EAMs. Esta lista se creó examinando listas diseñadas por otros autores, identificados a través de búsquedas bibliográficas en MEDLINE, LILACS y consultas con expertos. En Brasil, se registraron 55.604.537 admisiones hospitalarias en el SIH-SUS, entre 2008 y 2012, de las cuales 273.440 (0,49%) sufrieron al menos un EAM. Los porcentajes y tasas parecieron mantenerse constantes durante el periodo de estudio. Catorce de los 20 más frecuentes EAMs fueron identificados con códigos relacionados con enfermedades mentales. Las intoxicaciones fueron el segundo grupo registrado más común de EAMs en el SIH-SUS, representando 76.866 hospitalizaciones. La supervisión de EAMs en las bases de datos administrativas, usando los códigos CIE-10, es factible, incluso en países cuyos sistemas de información se encuentran en proceso de construcción, y puede ser un herramienta innovadora como complemento de las actuales estrategias de supervisión sobre medicamentos en Brasil, así como en otros países.

Interações medicamentosas potenciais entre medicamentos psicotrópicos dispensados / Potential drug-drug interactions between psychotropic drugs

RESUMO Objetivo Estimar a frequência e caracterizar as interações medicamentosas potenciais entre fármacos psicotrópicos sujeitos a controle especial pela portaria 344/98 da Agência Nacional de Vigilância Sanitária (Anvisa), os quais foram prescritos e dispensados em uma farmácia pública do Município de Cascavel, Paraná. Métodos Estudo retrospectivo com desenho seccional foi realizado em uma Farmácia Pública Municipal. A amostra foi composta por prescrições de medicamentos sujeitos a controle especial, dispensados entre primeiro de julho a 31 de agosto de 2010. As prescrições retidas na farmácia foram analisadas retrospectivamente e as informações, coletadas. As interações medicamentosas potenciais foram identificadas em 824 prescrições. Resultados As prescrições eram na maioria para pacientes do sexo feminino e com idade entre 19 e 59 anos. Em relação à especialidade do prescritor, 30,6% foram prescritas por psiquiatra. Em 77,9% das prescrições identificou-se pelo menos uma interação medicamentosa potencial. Foram descritas 54 diferentes interações medicamentosas potenciais, sendo 34 graves e 20 moderadas. Encontrou-se uma correlação linear entre medicamentos prescritos e interações medicamentosas potenciais (p valor < 0,001). Conclusão O presente estudo identificou uma alta frequência de interações medicamentosas potenciais envolvendo fármacos de controle especial e uma associação positiva entre o número de fármacos prescritos com a maior frequência dessas interações.

ABSTRACT Objective The aim of this study was to estimate the frequency and classify the potential drug-drug interactions that occur between psychotropic drugs subject to special control by Decree Order 344/98 of National Health Surveillance Agency (Anvisa), which were prescribed and were dispensed in a public pharmacy of the Cascavel City, Paraná. Methods A descriptive cross-sectional study was performed in a public community pharmacy in a city of Parana. The sample was the prescriptions of drugs subject to special control, dispensed between day 1 July 2010 to 31 August of the same year. The prescriptions retained in the public pharmacy were retrospectively analyzed and the information collected. The potential drug-drug interactions were identified in 824 prescriptions. Results The prescriptions were mostly for female patients, with aged between 19 and 59 years old. Regarding the prescriber specialty, psychiatrist prescribed 30.6% of prescriptions. In 77.9% of them at least one potential drug-interaction has been identified. Fifty-four different potential drug interactions have been reported, with 34 serious and 20 moderate. There was a linear correlation between prescribed medication and potential drug interactions (p < 0.001). Conclusion The present study showed a high frequency of potential drug interactions involving special control drugs and positive association between the number of drugs prescribed as often these interactions.

Uso de rastreadores para a identificação de eventos adversos a medicamentos* / The use of trigger toolsin the identification of adverse drug events / Uso de rastreadores para identificación de eventos adversos a medicamentos

É um desafio verificar se as estratégias voltadas para aumento da segurança no uso dos medicamentos são efetivas. Dessa maneira, mostra-se clara a necessidade de mecanismos para acompanhar estes resultados. A ferramenta "Global Trigger Tool for Measuring Adverse Events" do Institute for Healthcare Improvement foi desenvolvida para vencer este desafio. O uso de rastreadores para seleção de prontuários, com maior probabilidade de apresentarem eventos adversos, tem sido um método adotado por várias instituições de saúde, em vários países. O objetivo deste relato é descrever a experiência obtida na aplicação do módulo "Medicamento" desta ferramenta em um hospital público brasileiro no estado do Paraná. Realizada no período de novembro de 2012 a janeiro de 2015. A aplicação do método foi de baixo custo e viável para aplicação regular na Instituição (AU).

Checking whether the strategies aimed to improve the safety of drug use are effective is a major challenge. Therefore, the use of mechanisms to monitor these results is clearly necessary. The tool "Global Trigger Tool for Measuring Adverse Events" of the Institute for Healthcare Improvement has been developed to meet this challenge. The use of triggers in the selection of medical records with higher probability of showing adverse drug events (ADE) is adopted by health organizations in several countries. The present experience report aimed to describe the experience of application of the "Medication" module of this tool in a Brazilian public hospital in the state of Paraná. The experience was conducted from November 2012 to January 2015. It is a low-cost method that could be routinely used in the hospital (AU).

Verificar la efectividad de las estrategias para mejorar la seguridad en el uso de los medicamentos es un gran desafío. Así, hay una evidente necesidad de establecer modos de acompañar eses resultados. La herramienta "Global Trigger Tool for Measuring Adverse Events" del Institute for Healthcare Improvement fue desarrollada para vencer ese desafío. El uso de rastreadores para selección de prontuarios, con más probabilidad de presentar eventos adversos, viene siendo un método utilizado por variadas instituciones de salud, en distintos países. El objetivo de este relato es describir la experiencia obtenida en la aplicación del módulo "Medicamento" de esta herramienta en un hospital público brasileño en el estado de Paraná. El estudio fue realizado en el periodo de noviembre de 2012 a enero de 2015. La aplicación del método fue de bajo custo y viable para uso regular en la Institución (AU).

Adverse drug events identified by triggers at a teaching hospital in Brazil.

BACKGROUND: Adverse drug events (ADEs) are one of the most frequent causes of patient harm resulting from medical interventions, especially among inpatients. This study aimed to evaluate the incidence of ADEs and characterise them in terms of degree of harm, medication implicated and patient symptoms, at a Brazilian university hospital. METHODS: This is a retrospective study of chart review. The method, developed by the Institute for Healthcare Improvement, uses triggers to identify possible ADEs. The study population comprised adult inpatients at least 15 years old. Obstetric patients and those hospitalised for less than 48 hours were excluded. Time spent in the intensive care unit was not considered for the purposes of this study. Patients were selected on the basis of simple random sampling of records of patients discharged from January to July 2008. The records selected were reviewed by a multidisciplinary team. The indicators of ADE incidence were patients with ADEs and ADE rate per 100 patients. Patients with and without ADE were compared in the bivariate analysis. To identify the drugs classes most often associated with events, the number of prescriptions of each class of drug was related to the number of events assigned to it. RESULTS: The 240 inpatients studied were of mean age 50.8 (SD = 20.0) years, and mostly male (63.8%). A total of 44 ADEs were identified in 35 patient records, with 14.6% of patients presenting ADE and a rate of 18.3% ADEs per 100 patients. The most frequent were skin rash and nausea and vomiting, but severe ADEs were also identified. In the bivariate analysis long hospital stay and use of 10 or more drugs were associated with the occurrence of ADEs (p-value < 0.01). The drug classes associated with the highest number of events were anti-infective. CONCLUSION: About 1/6 of the hospitalized patients in a teaching hospital showed adverse events what is, by itself, cause for concern. Increased number of prescribed drugs and greater period of hospitalization appear to favour the occurrence of these events. In the future studies with higher number of patients may offer evidences of the association.

Eventos adversos a medicamentos em hospital terciario: estudo piloto com rastreadores / Eventos adversos a medicamentos en hospital terciario: estudio piloto con rastreadores / Adverse drug events in hospital: pilot study with trigger tool

OBJETIVO : Estimar a frequência e caracterizar os eventos adversos a medicamentos em hospital de cuidados terciários. MÉTODOS : Revisão retrospectiva de 128 prontuários de hospital do Rio de Janeiro, em 2007, representando 2.092 pacientes. A ferramenta utilizada foi uma lista de rastreadores, como antídotos, análises laboratoriais com resultados anormais, suspensão brusca de medicação e outros. Foi extraída amostra aleatória simples daqueles pacientes com 15 anos ou mais de idade. Foram excluídos pacientes oncológicos e da obstetrícia, e os internados por menos de 48 horas ou na emergência. Os pacientes com e sem eventos adversos a medicamentos foram comparados quanto a características sociais, demográficas e de doenças, para testar as diferenças entre os grupos. RESULTADOS : Cerca de 70,0% dos prontuários apresentaram no mínimo um rastreador. A capacidade dos rastreadores de identificar eventos adversos a medicamentos foi 14,4%. A incidência de eventos adversos a medicamentos foi 26,6/100 pacientes. Foram identificados um ou mais eventos em 15,6% dos pacientes. O tempo mediano de permanência hospitalar foi 35,2 dias para os pacientes com eventos adversos a medicamentos e 10,7 dias para os demais (p < 0,01). As classes de medicamentos mais envolvidos foram as que atuam sobre o aparelho cardiovascular e sobre o sistema nervoso, e os do trato digestivo e metabolismo. Os fármacos mais imputados foram: tramadol, dipirona, glibenclamida e furosemida. Do total de eventos, 82,0% contribuíram ou provocaram danos temporários ao paciente e demandaram intervenção, e 6,0% podem ter contribuído para o óbito do paciente. Estima-se que o hospital apresente, anualmente, 131 eventos de sonolência e lipotimia, 33 quedas e 33 hemorragias potencialmente associados aos medicamentos. CONCLUSÕES ...

OBJETIVO : Estimar la frecuencia y caracterizar los eventos adversos a medicamentos en hospital de cuidados terciarios. MÉTODOS : Revisión retrospectiva de 128 prontuarios de hospital de Rio de Janeiro, Brasil, en 2007, representando 2.092 pacientes. La herramienta utilizada fue una lista de rastreadores, como antídotos, análisis de laboratorio con resultados anormales, suspensión brusca de medicación y otros. Se extrajo muestra aleatoria simple de los pacientes con 15 años o más de edad. Se excluyeron pacientes oncológicos y de obstetricia, y los internados por menos de 48 horas o en la emergencia. Los pacientes con y sin eventos adversos a medicamentos fueron comparados con respecto a las características sociales, demográficas y de enfermedades, para evaluar las diferencias entre los grupos. RESULTADOS : Cerca de 70,0% de los prontuarios presentaron por lo menos un rastreador. La capacidad de los rastreadores para identificar eventos adversos a medicamentos fue de 14,4%. La incidencia fue 26,6/100 pacientes. Se identificaron uno o más eventos adversos a medicamentos en 15,6% de los pacientes. El tiempo mediano de permanencia hospitalaria fue de 35,2 días para los pacientes con eventos adversos a medicamentos y 10,7 días para los demás (p<0,01). Las clases de medicamentos más involucrados fueron los que actúan sobre los sistemas cardiovascular y nervioso y los del tracto digestivo y metabolismo. Los fármacos más imputados fueron: tramadol, dipirona, glibenclamida y furosemida. Del total de eventos, 82,0% contribuyeron o provocaron daños temporales en el paciente y demandaron intervención y 6,0% pueden haber contribuido en el óbito del paciente. Se estima que el hospital presente, anualmente, 131 eventos de somnolencia y lipotimia, 33 caídas y 33 hemorragias potencialmente asociados a los medicamentos. CONCLUSIONES ...

OBJECTIVE : To estimate the frequency of and to characterize the adverse drug events at a terciary care hospital. METHODS : A retrospective review was carried out of 128 medical records from a hospital in Rio de Janeiro in 2007, representing 2,092 patients. The instrument used was a list of triggers, such as antidotes, abnormal laboratory analysis results and sudden suspension of treatment, among others. A simple random sample of patients aged 15 and over was extracted. Oncologic and obstetric patients were excluded as were those hospitalized for less than 48 hours or in the emergency room. Social and demographic characteristics and those of the disease of patients who underwent adverse events were compared with those of patients who did not in order to test for differences between the groups. RESULTS : Around 70.0% of the medical records assessed showed at least one trigger. Adverse drug events triggers had an overall positive predictive value of 14.4%. The incidence of adverse drug events was 26.6 per 100 patients and 15.6% patients suffered one or more event. The median length of stay for patients suffering an adverse drug event was 35.2 days as against 10.7 days for those who did not (p < 0.01). The pharmacological classes most commonly associated with an adverse drug event were related to the cardiovascular system, nervous system and alimentary tract and metabolism. The most common active substances associated with an adverse drug event were tramadol, dypirone, glibenclamide and furosemide. Over 80.0% of events provoked or contributed to temporary harm to the patient and required intervention and 6.0% may have contributed to the death of the patient. It was estimated that in the hospital, 131 events involving drowsiness or fainting 33 involving falls, and 33 episodes of hemorrhage related to adverse drug effects occur annually. CONCLUSIONS : Almost one-sixth of in-patients (16,0%) suffered an adverse drug event. The instrument ...

[Adverse drug events in hospital: pilot study with trigger tool]. / Eventos adversos a medicamentos em hospital terciário: estudo piloto com rastreadores.

OBJECTIVE: To estimate the frequency of and to characterize the adverse drug events at a terciary care hospital. METHODS: A retrospective review was carried out of 128 medical records from a hospital in Rio de Janeiro in 2007, representing 2,092 patients. The instrument used was a list of triggers, such as antidotes, abnormal laboratory analysis results and sudden suspension of treatment, among others. A simple random sample of patients aged 15 and over was extracted. Oncologic and obstetric patients were excluded as were those hospitalized for less than 48 hours or in the emergency room. Social and demographic characteristics and those of the disease of patients who underwent adverse events were compared with those of patients who did not in order to test for differences between the groups. RESULTS: Around 70.0% of the medical records assessed showed at least one trigger. Adverse drug events triggers had an overall positive predictive value of 14.4%. The incidence of adverse drug events was 26.6 per 100 patients and 15.6% patients suffered one or more event. The median length of stay for patients suffering an adverse drug event was 35.2 days as against 10.7 days for those who did not (p < 0.01). The pharmacological classes most commonly associated with an adverse drug event were related to the cardiovascular system, nervous system and alimentary tract and metabolism. The most common active substances associated with an adverse drug event were tramadol, dypirone, glibenclamide and furosemide. Over 80.0% of events provoked or contributed to temporary harm to the patient and required intervention and 6.0% may have contributed to the death of the patient. It was estimated that in the hospital, 131 events involving drowsiness or fainting 33 involving falls, and 33 episodes of hemorrhage related to adverse drug effects occur annually. CONCLUSIONS: Almost one-sixth of in-patients (16.0%) suffered an adverse drug event. The instrument used may prove useful as a technique for monitoring and evaluating patient care results. Psycothropic therapy should be critically appraised given the frequency of associated events, such as excessive sedation, lethargy, and hypotension.

[Surveillance of adverse drug events in hospitals: implementation and performance of triggers]. / Vigilância de eventos adversos a medicamentos em hospitais: aplicação e desempenho de rastreadores.

Adverse drug events (ADE) are important causes of impairment of the quality of care for inpatients and therefore should be identified and characterized. Thus, lists of triggers were developed, including the proposal by the Institute for Healthcare Improvement. We analyzed the application of these triggers in a university hospital, with the cooperation of pharmacy and medical students, field training, standardized forms and manuals. Here, we present the process of application and performance of these triggers in a teaching hospital. The information on the triggers and ADE were collected through a retrospective chart review of patients discharged from January to June 2008. Four hundred and ninety-seven triggers were identified in 177 charts, and each chart had 2.33 (SD = 2.7) triggers on average. The most frequent triggers were: "antiemetic" (72.1/100 charts), "abrupt cessation of medication" (70.0/100 charts) and "over-sedation, drowsiness, numbness, lethargy, hypotension and fall" (34.6/100 charts). The most effective triggers for capturing ADE were "benzodiazepine antagonist", "antidiarrheal" and "rash", which, when identified in charts, were related to an event. The ADE most commonly found were related to the triggers, "abrupt cessation of medication" (8.3/100 charts), "antiemetic" (4.6/100 charts), "rash" and "anti-allergy" (2.1/100 charts). These results may help to decide which triggers are more useful in each situation.

Vigilância de eventos adversos a medicamentos em hospitais: aplicação e desempenho de rastreadores / Surveillance of adverse drug events in hospitals: implementation and performance of triggers

Os eventos adversos a medicamentos (EAMs) são causa importante de comprometimento da qualidade da atenção ao paciente hospitalizado e, por isso, devem ser identificados e caracterizados. Para tanto surgiram listas de rastreadores, entre elas a proposta pelo Institute for Healthcare Improvement. Aqui é apresentado o processo da aplicação dos rastreadores e o seu desempenho em um hospital de ensino. As informações sobre os rastreadores e os EAM foram coletadas por meio de revisão retrospectiva dos prontuários de pacientes com alta hospitalar de janeiro a junho de 2008. Foram identificados 497 rastreadores em 177 prontuários, onde cada prontuário apresentou, em média, 2,33 (DP = 2,7) rastreadores. Os encontrados com mais frequência foram: "antiemético" (72,1/100 prontuários), "interrupção abrupta da medicação" (70,0/100 prontuários) e "sedação excessiva, sonolência, torpor, letargia, queda e hipotensão" (34,6/100 prontuários). Os mais eficientes na captura de EAM (rendimento), isto é, aqueles que uma vez identificados sinalizaram possíveis eventos foram "antagonista de benzodiazepínico", "antidiarréicos" e "rash cutâneo". Os EAM mais encontrados foram relacionados aos rastreadores "interrupção abrupta da medicação" (8,3/100 prontuários), "antiemético" (4,6/100 prontuários) e "rash cutâneo" (2,1/100 prontuários). Essas considerações apontam para a utilidade do emprego da lista de rastreadores e podem contribuir para decidir sobre ajustes na sua aplicação.

Adverse drug events (ADE) are important causes of impairment of the quality of care for inpatients and therefore should be identified and characterized. Thus, lists of triggers were developed, including the proposal by the Institute for Healthcare Improvement. We analyzed the application of these triggers in a university hospital, with the cooperation of pharmacy and medical students, field training, standardized forms and manuals. Here, we present the process of application and performance of these triggers in a teaching hospital. The information on the triggers and ADE were collected through a retrospective chart review of patients discharged from January to June 2008. Four hundred and ninety-seven triggers were identified in 177 charts, and each chart had 2.33 (SD = 2.7) triggers on average. The most frequent triggers were: "antiemetic" (72.1/100 charts), "abrupt cessation of medication" (70.0/100 charts) and "over-sedation, drowsiness, numbness, lethargy, hypotension and fall" (34.6/100 charts). The most effective triggers for capturing ADE were "benzodiazepine antagonist", "antidiarrheal" and "rash", which, when identified in charts, were related to an event. The ADE most commonly found were related to the triggers, "abrupt cessation of medication" (8.3/100 charts), "antiemetic" (4.6/100 charts), "rash" and "anti-allergy" (2.1/100 charts). These results may help to decide which triggers are more useful in each situation.

Effect of tacrolimus (FK506) on ischemia-induced brain damage and memory dysfunction in rats.

The behavioral and neurohistological protective effects of tacrolimus (FK506) were examined in rats subjected to 15-min global forebrain ischemia. Learning and memory performance were evaluated in an aversive, non-food-motivated, eight-arm radial maze. In one experiment, naive rats were rendered ischemic, and 15 days later they were tested for acquisition of a spatial task (postoperative training). In a complementary experiment, rats were trained for 8 days and then subjected to ischemia (preoperative training); 15 days later (on Day 24 of testing) they were retested for retention of cognition. FK506 (1.0 mg/kg) was given intravenously at the beginning of reperfusion, followed by doses applied intraperitoneally 6, 24, 48 and 72 h postischemia. Behavioral performance was expressed by latency to find the goal box, and number of errors. Ischemia did not affect acquisition performance. In contrast, retention of cognition was markedly impaired by ischemia, particularly working memory (P<.05-.001). This ischemia-induced, retrograde amnesia was significantly reduced by FK506 compared to vehicle alone on Day 24, as measured by latency and working memory errors (P<.025). A neuroprotective effect of FK506 was also seen on working memory, when postischemic performance was compared to that prior to ischemia (P>.05, Day 24 vs. Day 8, paired samples), in contrast to the significant, retrograde amnesia found in the ischemic, vehicle-treated group (P<.01). FK506 also significantly reduced the extent of hippocampal CA1 cell loss; however, this effect did not correlate with behavior. The present results suggest that the histological, neuroprotective effect of FK506 may be accompanied by a reduction in cognitive impairment, as assessed in a novel, non-food-motivated, eight-arm radial maze after transient, global, cerebral ischemia in rats.