Use of antimicrobials in pediatric wards of five Brazilian hospitals.

The use of antimicrobials (AMs) in pediatric infections is common practice and use may be inappropriate leading to antimicrobial resistance. Off-label AM use is also common in this group and can result in drug-related problems. There is lack of DUR data in Brazil and in Latin America, specially for AM pediatric use. The aim of this study was to describe the utilization of AMs in hospitalized children in five hospitals in Brazil. We conducted an observational study of the utilization of AMs in pediatric wards in hospitals in the states of Ceará (CE), Sergipe (SE), Rio de Janeiro (RJ), Rio Grande do Sul (RS) and the Federal District (DF). Data derived from patient medical records and prescriptions were collected over a six-month period in each hospital. The number of AMs used by each patient was recorded, and AM use was assessed using Days of therapy (DOT) and Length of therapy (LOT) per 1000 patient days according to different patient characteristics. Off-label (OL) use was described according to age. The study analyzed data from 1020 patients. The sex and age distributions were similar across the five hospitals. However, differences were found for comorbidities, history of ICU admission and length of hospital stay. The most common diseases were respiratory tract infections. There were wide variations in DOT/1000PD (278-517) and LOT/1000PD (265-390). AM utilization was highest in the hospital in SE. The consumption of second-generation penicillins and cephalosporins was high. The prevalence of OL use of AMs was higher for patients in the RJ hospital, in infants, in patients who underwent prolonged hospital stays, and in patients who used multiple AMs. The AM that showed the highest prevalence of OL use was azithromycin, in both oral and parenteral formulations. Overall AM use was high and showed differences in each setting, possibly influenced by local characteristics and by prescribing standards adopted by pediatricians.

Adverse reactions to antimicrobials in pediatric patients admitted to a tertiary hospital: a cohort study.

BACKGROUND: Antimicrobials are widely used in hospitals and are often associated with adverse drug reactions (ADRs). The objective of this study was to determine the incidence of ADRs caused by antimicrobials and classify them according to the type of reaction, the class of antimicrobials used, causality, severity and avoidability. METHODS: A prospective cohort study was carried out with paediatric patients for 6 months. Causality was verified using the Naranjo and Liverpool algorithms, the severity was verified with the adapted scale of Hartwig and the avoidability was verified with the Liverpool Avoidability Assessment Tool. RESULTS: A total of 303 patients were followed, and 18.2% (55/303) of them had one or more ADRs during the hospital stay. Just over half of the patients (28/55) had diarrhea. The most used antimicrobials were beta-lactams and second-generation cephalosporins. Suspicions were classified mainly as possible 78.6% (55/70) according to the Naranjo algorithm, and as probable 48.6% (34/70) according to the Liverpool algorithm. The antimicrobial most involved with ADRs was cefepime. The risk of manifesting ADR was greater with the use of some antimicrobials such as clindamycin (relative risk (RR) 3.0, CI 1.67 to 5.4), as well as with the increase in hospitalisation days (OR 1.022, CI 1.008 to 1.036) and in the number of antimicrobials prescribed (OR 1.649, CI 1.360 to 2.001). CONCLUSION: ADRs were observed in approximately one-fifth of patients and were mostly gastrointestinal, moderate, unavoidable and with variable causality, depending on the algorithm used.

Adverse Drug Reactions to Anti-infectives in Hospitalized Children: A Multicenter Study in Brazil.

INTRODUCTION: Adverse drug reactions (ADRs) to anti-infectives affect especially hospitalized children and contribute to increased morbidity, mortality, length of stay, and costs in healthcare systems. OBJECTIVE: To assess ADRs associated with anti-infective use in Brazilian hospitalized children. METHODS: A prospective cohort study was conducted in 5 public hospitals over 6 months. Children aged 0-11 years and 11 months who were hospitalized for more than 48 h and prescribed anti-infectives for over 24 h were included. RESULTS: A total of 1020 patients met the inclusion criteria. Of these, 152 patients experienced 183 suspected ADRs. Most reactions were related to the gastrointestinal system (65.6%), followed by skin reactions (18.6%). Most reactions were classified as probable causality (58.5%), moderate severity (61.1%), and unavoidable (56.2%). Our findings showed that ADRs were associated with increased length of stay (P < .001), increased length of therapy (P < .015), increased days of therapy (P = .038), and increased number of anti-infectives prescribed per patient (P < .001). CONCLUSION: Almost 15% of hospitalized children exposed to anti-infectives presented suspected ADRs. Their occurrence was classified as probable, of moderate severity, and unavoidable. ADRs were significantly influenced by the length of hospital stay and the number of anti-infectives prescribed per patient.

Assessment and comparison of anticholinergic exposure in older adults at a Basic Health Unit in Porto Alegre / Avaliação e comparação da exposição anticolinérgica em idosos de uma Unidade Básica de Saúde de Porto Alegre

Objectives: To estimate the anticholinergic burden in geriatric patients using two scales and to assess the degree of agreement between them. Methods: Data from an observational study conducted in a primary health care service were used. Anticholinergic burden was assessed using the Belgian Scale Muscarinic Acetylcholinergic Receptor ANTagonist Exposure Scale and the Brazilian Scale of Medicines with Anticholinergic Activity. The cumulative anticholinergic burden score was classified using a categorical approach: Brazilian scale (0: none; 1 ­ 2: low; ≥ 3: high) and Belgian scale (0: none; 0.5 ­ 1.5: low; ≥ 2: high). The degree of agreement between the two instruments was obtained through Cohen's kappa coefficient. Results: A total of 374 older people were included, most of them female and aged between 60 and 69 years. At least one potentially inappropriate drug with anticholinergic activity was used by 60.70% of patients according to the Brazilian scale and 32.89% by the Belgian scale. On average, 20.85% were under high anticholinergic exposure. Overall, on both scales, the most commonly recurrent medications were those indicated for the treatment of psychiatric disorders. Agreement between the scales was moderate (Kappa = 0.43). Conclusions: A high percentage of older adults was exposed to drugs with an anticholinergic burden, posing risks to health and quality of life. Consensus is needed on how anticholinergic burden is calculated by these scores, as well as standardization of the list of included drugs.

Objetivos: Estimar a carga anticolinérgica em idosos com base em duas escalas e avaliar o grau de concordância entre estas. Metodologia: Foram utilizados dados de um estudo observacional realizado em um serviço de atenção primária. A carga anticolinérgica foi avaliada pela escala belga Muscarinic Acetylcholinergic Receptor ANTagonist Exposure Scale e da Escala Brasileira de Medicamentos com Atividade Anticolinérgica. A pontuação da carga anticolinérgica cumulativa foi classificada utilizando uma abordagem categórica: escala brasileira (0: nenhuma, 1 ­ 2: baixa, ≥ 3: alta) e escala belga (0: nenhuma, 0,5 ­ 1,5: baixa, ≥ 2: alta). O grau de concordância entre as duas ferramentas foi obtido por meio do coeficiente Capa de Cohen. Resultados: Foram incluídos 374 idosos, a maioria do sexo feminino e com idade entre 60 a 69 anos. O uso de pelo menos um medicamento potencialmente inapropriado com atividade anticolinérgica foi verificado em 60,70% dos idosos com a aplicação da escala brasileira e em 32,89% com a escala belga. Em média, 20.85% estavam sob alta exposição anticolinérgica. De modo geral, os medicamentos mais recorrentes, para ambas as escalas, foram os indicados para o tratamento de transtornos psiquiátricos. A concordância entre as escalas foi moderada (Capa = 0,43). Conclusão: Um percentual elevado de idosos estava exposto a medicamentos com carga anticolinérgica, representando riscos para a saúde e a qualidade de vida. É necessário um consenso sobre como calcular a carga anticolinérgica nos diferentes escores, bem como a padronização da lista de medicamentos incluídos.

Cross-cultural adaptation, validation and reliability of the Medication Safety Thermometer tool for use in Brazil.

OBJECTIVES: to perform cross-cultural adaptation, face and content validation and reliability analysis of the Medication Safety Thermometer tool for use in Brazil. METHODS: the process of cross-cultural adaptation and validation followed the stages of translation, synthesis of translations, back-translation, content validation performed by experts, and face validation through pre-testing. Reliability was determined by calculating the Kappa coefficient. RESULTS: the two translated versions were synthesized into a single version, which was back-translated and showed no divergences. The expert committee judged the adapted tool as equivalent, reaching a Content Validity Index higher than 0.8. The mean global understanding was 1.82, demonstrating face validity. The assessed items had Kappa coefficient greater than 0.61, showing agreement between observers. CONCLUSIONS: the cross-cultural adaptation of the tool was performed following an established methodology. The adapted tool showed inter-rater reliability and validity for use in Brazil.

Conhecimento dos prescritores sobre medicamentos potencialmente inapropriados para idosos em uma Unidade Básica de Saúde / Prescribers' knowledge of potentially inappropriate medications in older adults in a Primary Care Unit

Introdução: O conhecimento dos prescritores sobre medicamentos potencialmente inapropriados (MPI) pode reduzir o risco de resultados adversos à saúde em idosos, uma vez que esses medicamentos podem trazer mais risco do que benefício a esses pacientes. O objetivo deste estudo é obter informações sobre o conhecimento dos prescritores em relação aos cuidados na prescrição de medicamentos para idosos e analisar o conhecimento destes em relação a critérios explícitos de classificação de MPI.Métodos: Trata-se de um estudo exploratório e observacional, de delineamento transversal, desenvolvido com a aplicação de questionário on-line respondido de forma anônima por prescritores de uma unidade básica de saúde.Resultados: Dos 20 profissionais que responderam ao questionário, 9 eram professores, 7 médicos residentes e 4 médicos contratados. Em relação aos idosos, 70% dos prescritores percebem boa adesão ao tratamento e 40% maior frequência de reações adversas a medicamentos, quando comparados à população em geral. Somente 30% dos profissionais relataram conhecimento sobre algum critério de classificação de MPI, e 25% destes já utilizou/utiliza algum dos critérios na prática clínica. Porém, os prescritores citaram as classes mais presentes no Critério de Beers para MPI como candidatas à desprescrição e ajuste de dose.Conclusão: O conhecimento e aplicação de critérios de classificação de MPI na prática clínica é ainda incipiente, mesmo em Unidade vinculada a Hospital Universitário.

Introduction: Knowledge of potentially inappropriate medications (PIMs) may reduce the risk of adverse health outcomes in older patients, given that PIMs may be more harmful than beneficial to this population. To investigate prescribers' knowledge of appropriate drug prescription in older adults and evaluate their knowledge of explicit criteria for PIM classification.Methods: We conducted a cross-sectional, exploratory, observational study. We developed an online questionnaire, which was anonymously answered by prescribers from a primary care unit.Results: A total of 20 prescribers answered the questionnaire, of whom 9 were professors, 7 were medical residents, and 4 were physicians. In older patients, 70% of prescribers reported good adherence to treatment and 40% reported a higher rate of adverse drug reactions compared with the general population. Only 30% of prescribers reported some knowledge of the criteria for PIM classification, and 25% of them had already used/use some of the criteria in clinical practice. However, the most prevalent drug classes in the Beers Criteria for PIM were mentioned by prescribers as potentially requiring deprescription and dose adjustment.Conclusion: Knowledge and application of the PIM classification in clinical practice is still incipient, even in a primary care unit affiliated with a teaching hospital.

Bleeding associated with self-medication in warfarin users: A prospective observational study in Ijuí (Brazil)

Abstract Warfarin has been associated with bleeding and venous thromboembolism. Objective: This study aimed to estimate the association between bleeding and concomitant self-medication, and the incidence of adverse drug reactions in patients using warfarin. Setting: the public health network of Ijuí, a municipality in southern Brazil. This was an open prospective cohort, conducted for a period of 18 months with users of warfarin, treated at the public health service. The association between bleeding and self-medication was evaluated by means of the Cox Model with left truncation, using the time variable. Main outcome measurement: bleeding reported in the follow-up. Cases of thromboembolism and death were also registered. All patients treated with warfarin in the public health system of the municipality (98) were identified. Sixty-eight were interviewed and followed up, of whom 63 completed follow-up and five died during the study. Bleeding rates of 37.7 /100 patients/year, thromboembolism of 4.8/100 patients / year and deaths of 4.8 /100 patients / year were observed. The results showed that patients, who take warfarin and self-medicated present a two-fold increased bleeding, compared with those who do not self-medicate. The bleeding risk associated with self-medication ranged from 2.001 to 2.685; those values maintained their significance even when adjusted for number of interactions, CYP polymorphism, TTR and age in COX analysis. These results greatly suggest the need for providing greater assistance to patients who take anticoagulant medications with the purpose of reducing self-medication and consequently, adverse reactions.

Cross-cultural adaptation, validation and reliability of the Medication Safety Thermometer tool for use in Brazil / Adaptación transcultural, validez y confiabilidad de la herramienta Medication Safety Thermometer para uso en Brasil / Adaptação transcultural, validação e confiabilidade da ferramenta Medication Safety Thermometer para uso no Brasil

ABSTRACT Objectives: to perform cross-cultural adaptation, face and content validation and reliability analysis of the Medication Safety Thermometer tool for use in Brazil. Methods: the process of cross-cultural adaptation and validation followed the stages of translation, synthesis of translations, back-translation, content validation performed by experts, and face validation through pre-testing. Reliability was determined by calculating the Kappa coefficient. Results: the two translated versions were synthesized into a single version, which was back-translated and showed no divergences. The expert committee judged the adapted tool as equivalent, reaching a Content Validity Index higher than 0.8. The mean global understanding was 1.82, demonstrating face validity. The assessed items had Kappa coefficient greater than 0.61, showing agreement between observers. Conclusions: the cross-cultural adaptation of the tool was performed following an established methodology. The adapted tool showed inter-rater reliability and validity for use in Brazil.

RESUMEN Objetivos: realizar adaptación transcultural, validez facial y contenido y análisis de confiabilidad de la herramienta Medication Safety Thermometer para uso en Brasil. Métodos: el proceso de adaptación transcultural y validez siguió las etapas de traducción, síntesis de las traducciones, retro-traducción, validez de contenido realizada por especialistas y validez facial mediante el pretest. La confiabilidad fue determinada por el cálculo del coeficiente de Kappa. Resultados: las dos versiones traducidas fueron sintetizadas en una única versión, que fue retro-traducida y no demostró divergencias. El comité de expertos juzgó la herramienta adaptada como equivalente, alcanzando Índice de Validez de Contenido mayor que 0,8. La mediana de comprensión global fue de 1,82, demostrando validez facial. Los ítems evaluados presentaron coeficiente de Kappa mayor que 0,61, evidenciando concordancia entre observadores. Conclusiones: la adaptación transcultural de la herramienta fue realizada siguiendo metodología establecida. La herramienta adaptada mostró confiabilidad entre observadores y validez para utilización en Brasil.

RESUMO Objetivos: realizar adaptação transcultural, validação de face e conteúdo e análise da confiabilidade da ferramenta Medication Safety Thermometer para uso no Brasil. Métodos: o processo de adaptação transcultural e validação seguiu as etapas de tradução, síntese das traduções, retrotradução, validação de conteúdo realizada por especialistas e validação de face mediante o pré teste. A confiabilidade foi determinada pelo cálculo do coeficiente de Kappa. Resultados: as duas versões traduzidas foram sintetizadas em uma única versão, que foi retrotraduzida e não demonstrou divergências. O comitê de experts julgou a ferramenta adaptada como equivalente, alcançando Índice de Validade de Conteúdo maior que 0,8. A média de compreensão global foi de 1,82, demonstrando validade de face. Os itens avaliados apresentaram coeficiente de Kappa maior que 0,61, evidenciando concordância entre observadores. Conclusões: a adaptação transcultural da ferramenta foi realizada seguindo metodologia estabelecida. A ferramenta adaptada mostrou confiabilidade entre observadores e validade para utilização no Brasil.

Polymorphism of the CYP2C9 and VKORC1 genes in patients on the public health system of a municipality in Southern Brazil.

BACKGROUND: Genetic factors can be responsible for part of the populational and interindividual differences observed in warfarin users. OBJECTIVES: To identify occurrence of polymorphisms of the CYP2C9 and VKORC1 genes in patients taking warfarin and relate these profiles to their medication dosages and the Time in Therapeutic Range (TTR). METHODS: Monthly interviews were conducted for data collection. Data were collected on demographic characteristics and medications in use, especially warfarin, including reason for prescription and weekly dose. TTR was calculated as the percentage of days with international normalized ratio (INR) between 2 and 3. The CYP2C9 and VKORC1 genes were analyzed at a Human Genetics Laboratory. RESULTS: 49 patients (74.2%) had polymorphisms of the CYP2C9 and/or VKORC1 genes; the remaining 17 (25.8%) did not have these polymorphisms. The average weekly dose of warfarin was lower among those who had a polymorphism for any of the genes compared to those who did not, with a significant difference (p = 0.035). The mean TTR was also lower among patients with polymorphism. However, the difference between the two groups was not significant for this variable (p = 0.438). CONCLUSIONS: An association was observed between the polymorphisms and the warfarin doses taken by the patients. However, there was no association with adverse events or the time spent within the therapeutic range in this sample.

CONTEXTO: Fatores genéticos podem ser responsáveis por parte das diferenças populacionais e interindividuais observadas em usuários de varfarina. OBJETIVOS: Identificar a ocorrência de polimorfismo dos genes CYP2C9 e VKORC1 em pacientes em uso de varfarina e relacionar esses perfis com a dose do medicamento e o tempo no intervalo terapêutico. MÉTODOS: Foram realizadas entrevistas mensais para a coleta de dados. Foram reunidos dados sobre características demográficas e medicamentos em uso, principalmente sobre varfarina, como motivo da prescrição e dose semanal. O tempo no intervalo terapêutico foi calculado como a porcentagem de dias com razão normalizada internacional entre os valores 2 e 3. Os genes CYP2C9 e VKORC1 foram analisados em laboratório de Genética Humana. RESULTADOS: Entre os participantes, 49 pacientes (74,2%) apresentaram polimorfismo dos genes CYP2C9 e/ou VKORC1; os 17 restantes (25,8%) não apresentaram esses polimorfismos. A dose média semanal de varfarina foi menor entre os que apresentaram polimorfismo para algum dos genes em comparação aos que não apresentaram, com diferença significativa (p = 0,035). O tempo no intervalo terapêutico médio também foi menor entre os pacientes com polimorfismo. Porém, não houve diferença significativa entre os dois grupos para essa variável (p = 0,438). CONCLUSÕES: Foi observada associação entre os polimorfismos e a dose de varfarina utilizada pelos pacientes; no entanto, não houve associação com eventos adversos e o tempo de permanência na faixa terapêutica nessa amostra.

Polymorphism of the CYP2C9 and VKORC1 genes in patients on the public health system of a municipality in Southern Brazil / Polimorfismo dos genes CYO2C9 e VKORC1 em pacientes do Sistema Público de Saúde em um município do Sul do Brasil

Abstract Background Genetic factors can be responsible for part of the populational and interindividual differences observed in warfarin users. Objectives To identify occurrence of polymorphisms of the CYP2C9 and VKORC1 genes in patients taking warfarin and relate these profiles to their medication dosages and the Time in Therapeutic Range (TTR). Methods Monthly interviews were conducted for data collection. Data were collected on demographic characteristics and medications in use, especially warfarin, including reason for prescription and weekly dose. TTR was calculated as the percentage of days with international normalized ratio (INR) between 2 and 3. The CYP2C9 and VKORC1 genes were analyzed at a Human Genetics Laboratory. Results 49 patients (74.2%) had polymorphisms of the CYP2C9 and/or VKORC1 genes; the remaining 17 (25.8%) did not have these polymorphisms. The average weekly dose of warfarin was lower among those who had a polymorphism for any of the genes compared to those who did not, with a significant difference (p = 0.035). The mean TTR was also lower among patients with polymorphism. However, the difference between the two groups was not significant for this variable (p = 0.438). Conclusions An association was observed between the polymorphisms and the warfarin doses taken by the patients. However, there was no association with adverse events or the time spent within the therapeutic range in this sample.

Resumo Contexto Fatores genéticos podem ser responsáveis por parte das diferenças populacionais e interindividuais observadas em usuários de varfarina. Objetivos Identificar a ocorrência de polimorfismo dos genes CYP2C9 e VKORC1 em pacientes em uso de varfarina e relacionar esses perfis com a dose do medicamento e o tempo no intervalo terapêutico. Métodos Foram realizadas entrevistas mensais para a coleta de dados. Foram reunidos dados sobre características demográficas e medicamentos em uso, principalmente sobre varfarina, como motivo da prescrição e dose semanal. O tempo no intervalo terapêutico foi calculado como a porcentagem de dias com razão normalizada internacional entre os valores 2 e 3. Os genes CYP2C9 e VKORC1 foram analisados em laboratório de Genética Humana. Resultados Entre os participantes, 49 pacientes (74,2%) apresentaram polimorfismo dos genes CYP2C9 e/ou VKORC1; os 17 restantes (25,8%) não apresentaram esses polimorfismos. A dose média semanal de varfarina foi menor entre os que apresentaram polimorfismo para algum dos genes em comparação aos que não apresentaram, com diferença significativa (p = 0,035). O tempo no intervalo terapêutico médio também foi menor entre os pacientes com polimorfismo. Porém, não houve diferença significativa entre os dois grupos para essa variável (p = 0,438). Conclusões Foi observada associação entre os polimorfismos e a dose de varfarina utilizada pelos pacientes; no entanto, não houve associação com eventos adversos e o tempo de permanência na faixa terapêutica nessa amostra.

Polymorphism of the CYP2C9 and VKORC1 genes in patients on the public health system of a municipality in Southern Brazil / Polimorfismo dos genes CYO2C9 e VKORC1 em pacientes do Sistema Público de Saúde em um município do Sul do Brasil

Abstract Background Genetic factors can be responsible for part of the populational and interindividual differences observed in warfarin users. Objectives To identify occurrence of polymorphisms of the CYP2C9 and VKORC1 genes in patients taking warfarin and relate these profiles to their medication dosages and the Time in Therapeutic Range (TTR). Methods Monthly interviews were conducted for data collection. Data were collected on demographic characteristics and medications in use, especially warfarin, including reason for prescription and weekly dose. TTR was calculated as the percentage of days with international normalized ratio (INR) between 2 and 3. The CYP2C9 and VKORC1 genes were analyzed at a Human Genetics Laboratory. Results 49 patients (74.2%) had polymorphisms of the CYP2C9 and/or VKORC1 genes; the remaining 17 (25.8%) did not have these polymorphisms. The average weekly dose of warfarin was lower among those who had a polymorphism for any of the genes compared to those who did not, with a significant difference (p = 0.035). The mean TTR was also lower among patients with polymorphism. However, the difference between the two groups was not significant for this variable (p = 0.438). Conclusions An association was observed between the polymorphisms and the warfarin doses taken by the patients. However, there was no association with adverse events or the time spent within the therapeutic range in this sample.

Resumo Contexto Fatores genéticos podem ser responsáveis por parte das diferenças populacionais e interindividuais observadas em usuários de varfarina. Objetivos Identificar a ocorrência de polimorfismo dos genes CYP2C9 e VKORC1 em pacientes em uso de varfarina e relacionar esses perfis com a dose do medicamento e o tempo no intervalo terapêutico. Métodos Foram realizadas entrevistas mensais para a coleta de dados. Foram reunidos dados sobre características demográficas e medicamentos em uso, principalmente sobre varfarina, como motivo da prescrição e dose semanal. O tempo no intervalo terapêutico foi calculado como a porcentagem de dias com razão normalizada internacional entre os valores 2 e 3. Os genes CYP2C9 e VKORC1 foram analisados em laboratório de Genética Humana. Resultados Entre os participantes, 49 pacientes (74,2%) apresentaram polimorfismo dos genes CYP2C9 e/ou VKORC1; os 17 restantes (25,8%) não apresentaram esses polimorfismos. A dose média semanal de varfarina foi menor entre os que apresentaram polimorfismo para algum dos genes em comparação aos que não apresentaram, com diferença significativa (p = 0,035). O tempo no intervalo terapêutico médio também foi menor entre os pacientes com polimorfismo. Porém, não houve diferença significativa entre os dois grupos para essa variável (p = 0,438). Conclusões Foi observada associação entre os polimorfismos e a dose de varfarina utilizada pelos pacientes; no entanto, não houve associação com eventos adversos e o tempo de permanência na faixa terapêutica nessa amostra.

Off-label use of drugs by age in Brazilian children: a population study. / Uso off-label de medicamentos segundo a idade em crianças brasileiras: um estudo populacional.

OBJECTIVE: To estimate the prevalence of off-label drug use by age in children 12 years old and younger in Brazil. METHOD: Population-based cross-sectional study (National Survey on Access, Use and Promotion of Rational Use of Medicines - PNAUM), including 7,528 children aged 12 years or younger. Face-to-face interviews were used to collect the data in the domiciles. The age-related off-label classification was carried out using the electronic medication compendium of National Agency of Sanitary Surveillance (ANVISA). Sociodemographic characteristics, presence of chronic disease, use of health services and characteristics of the informant were collected. Data were expressed by relative frequencies and 95% confidence intervals. Pearson's chi-square test was used to evaluate the statistical significance of the differences between the groups, with a significance level of 5%. Main outcome measure was the prevalence of off-label use. RESULTS: The prevalence of off-label use by age was 18.7% (95%CI 16.4 - 21.3). Children younger than 2 years old presented the highest prevalence of off-label use. The most frequently used off-label drugs by age were amoxicillin, nimesulide and the combination of phenylephrine and brompheniramine. CONCLUSION: The off-label use of drugs by age is common in the Brazilian pediatric population, especially among children under two years old.

Potentially inappropriate medications for older adults in a primary healthcare unit in southern Brazil.

Background Potentially inappropriate medications for older adults are those that offer more risks than benefits for this population. Such medications found in older adults' prescriptions across the world are associated with higher rates of comorbidities and hospitalizations, along with high expenditure on healthcare resources. Objectives To estimate the frequency of older adults using potentially inappropriate medications according to four different criteria, to identify factors associated with the use of such medicines and differences between the tools. Setting A primary healthcare unit linked to a university hospital in Porto Alegre, Brazil. Method This was a cross-sectional study conducted via data collection from the electronic medical records of 390 older adults. The information collected comprised sex, age, chronic diseases diagnosed and medications used. The dependent variable of the study was the use of at least one potentially inappropriate medication, according to the following criteria: Beers, Screening Tool of Older Persons' Prescriptions (STOPP), Brazilian consensus and Anticholinergic Risk Scale (ARS). Main outcome measurement Prevalence of inappropriate medication, differences between the tools and associated factors. Results: The use of at least one potentially inappropriate medication was found in 55.1% of the sample according to the Beers criterion, 51.3% according to the Brazilian consensus, 42.6% according to STOPP and 23.6% according to ARS. It was also seen that 14.9% of the studied population was exposed to a very strong anticholinergic risk. Depending on which tools were used, the agreement observed between the criteria was considered high, moderate, or low. Regarding the four criteria, the use of potentially inappropriate medication is associated with polypharmacy, the diagnosis of three or more chronic diseases and the presence of neuropsychiatric and musculoskeletal diseases. Conclusion Among the older adult population studied, the prevalence of potentially anappropriate medication is high, according to the four different classification criteria used. As a more specific tool, the agreement between Anticholinergic Risk Scale and other criteria was lower, but it can be an important complement to other lists.

Detecção de eventos adversos relacionados a medicamentos por meio das ferramentas Global Trigger Tool e Medication Safety Thermometer: uma revisão narrativa / Detection of adverse drug events using the Global Trigger Tool and the Medication Safety Thermometer: a narrative review

Eventos adversos (EA) são incidentes que resultam em dano ao paciente e representam um problema global. Estima-se que um em cada 10 pacientes sofram algum tipo de EA durante sua hospitalização. EA relacionados a medicamentos são a segunda causa mais frequente e a maior causa de danos evitáveis causados aos pacientes mundialmente. Esforços no sentido de evitá-los são de extrema importância, para tanto, é indispensável a mensuração dos eventos e danos associados. Ferramentas comoGlobal Trigger Tool(GTT) eMedication Safety Thermometer (MedST) vêm sendo utilizadas para identificação e mensuração de EA relacionados a medicamentos, visando projeção de sistemas de saúde mais seguros. Este trabalho consiste em uma revisão narrativa da literatura, de caráter descritivo com enfoque nas vantagens e limitações das ferramentas GTT e MedST, vislumbrando contribuir com a literatura acerca da segurança no uso de medicamentos e encorajar o desenvolvimento e/ou adaptação transcultural e validação de ferramentas com esta finalidade para uso no Brasil. A ferramenta GTT possui caráter retrospectivo, o que inviabiliza ações preventivas e está limitada a apenas uma fonte de dados, o prontuário do paciente, diferente da MedST, que permite a mensuração prospectiva, possibilitando intervenções imediatas e busca das informações em diferentes fontes de dados. (AU)

Adverse events (AE) are incidents that result in harm to the patient and represent a global problem. Estimates show that one in 10 patients experience some type of AE during hospitalization. Adverse drug events are the second most common cause and the biggest cause of preventable harm to patients worldwide. Efforts to avoid them are extremely important; therefore, measurement of events and associated harms is essential. Tools such as the Global Trigger Tool (GTT) and the Medication Safety Thermometer (MedST) have been increasingly used for the identification and measurement of adverse drug events, aiming at the design of safer health systems. This paper consists of a narrative review of the literature focusing on the description of advantages and limitations of both the GTT and the MedST. The aim is to contribute to the literature on safer use of medications and to encourage the development and/or cross-cultural adaptation and validation of adequate tools for use in Brazil. The GTT is a retrospective tool, hindering preventive actions, and is limited to only one data source, i.e., the patient's medical record. Conversely, the MedST provides prospective measurement, allowing immediate interventions, and search for information in different data sources. (AU)

Uso off-label de medicamentos segundo a idade em crianças brasileiras: um estudo populacional / Off-label use of drugs by age in Brazilian children: a population study

RESUMO: Objetivo: Estimar a prevalência de uso off-label de medicamentos segundo a idade em crianças de 0 a 12 anos no Brasil. Métodos: Estudo transversal de base populacional (Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos - PNAUM), incluindo 7.528 crianças de 0 a 12 anos de idade. Entrevistas individuais face a face foram utilizadas para coletar os dados nos domicílios. A classificação off-label segundo a idade foi realizada por meio de consulta ao compêndio eletrônico da Agência Nacional de Vigilância Sanitária (ANVISA). Características sociodemográficas, presença de doença crônica, uso de serviços de saúde e características do informante foram coletadas. Os dados foram expressos por frequências relativas e intervalos de confiança de 95% (IC95%). O teste do χ2 de Pearson foi usado para avaliar a significância estatística das diferenças entre os grupos, com um nível de significância de 5%. A principal medida de desfecho foi a prevalência de uso off-label segundo a idade. Resultados: A prevalência de uso off label por idade foi de 18,7% (IC95% 16,4 - 21,3). Crianças com menos de 2 anos apresentaram maior prevalência desse uso em relação às mais velhas. Os medicamentos com maior frequência de uso off-label segundo a idade foram amoxicilina, nimesulida e a combinação de fenilefrina com bronfeniramina. Conclusão: O uso off-label de medicamentos segundo a idade é comum na população pediátrica brasileira, especialmente nas crianças menores de 2 anos de idade.

Abstract: Objective: To estimate the prevalence of off-label drug use by age in children 12 years old and younger in Brazil. Method: Population-based cross-sectional study (National Survey on Access, Use and Promotion of Rational Use of Medicines - PNAUM), including 7,528 children aged 12 years or younger. Face-to-face interviews were used to collect the data in the domiciles. The age-related off-label classification was carried out using the electronic medication compendium of National Agency of Sanitary Surveillance (ANVISA). Sociodemographic characteristics, presence of chronic disease, use of health services and characteristics of the informant were collected. Data were expressed by relative frequencies and 95% confidence intervals. Pearson's chi-square test was used to evaluate the statistical significance of the differences between the groups, with a significance level of 5%. Main outcome measure was the prevalence of off-label use. Results: The prevalence of off-label use by age was 18.7% (95%CI 16.4 - 21.3). Children younger than 2 years old presented the highest prevalence of off-label use. The most frequently used off-label drugs by age were amoxicillin, nimesulide and the combination of phenylephrine and brompheniramine. Conclusion: The off-label use of drugs by age is common in the Brazilian pediatric population, especially among children under two years old.

Knowledge and information levels and adherence to oral anticoagulant therapy with warfarin in patients attending primary health care services.

BACKGROUND: Oral anticoagulation therapy with warfarin is widely used around the world and its safety and efficacy are well-established. Nevertheless, anticoagulants are among the drug classes most associated with fatal medication errors in primary health care. OBJECTIVE: To investigate patient knowledge, the level of information provided, and medication adherence in patients treated with warfarin at a primary health care service. METHOD: A cross-sectional study of a prospective cohort of 60 patients on warfarin treatment in the town of Ijuí, Rio Grande do Sul, Brazil. A questionnaire was administered to test patients' knowledge about their prescriptions and the level of information provided by the health team. The 8-item Morisky Medication Adherence Scale (MMAS-8) and International Normalized Ratio (INR) were used to verify adherence to treatment. RESULTS: The results were expressed in absolute and relative values and prevalence ratios were calculated, with respective 95% confidence intervals. It was found that 83.3% of the participants had been given insufficient information by the health team, 50% did not know how to use the medication correctly, 86.7% were not adherent to the treatment according to MMAS-8 and 63.3% were outside of the correct INR range. CONCLUSION: In this study, we observed a need to improve the quality of information provided to users and to develop strategies to improve adherence to treatment, to ensure the safety of patients treated with warfarin in primary health care services.

Drug-Related Morbidity in Brazil: A Cost-of-Illness Model.

OBJECTIVES: To estimate the proportion of patients with drug-related morbidities (DRMs), DRM preventability, and the cost of illness of the DRMs in Brazil. METHODS: We used the decision-analytic model initially developed by Johnson and Bootman (Drug-related morbidity and mortality. A cost-of-illness model. J Manag Care Pharm 1996;2:39-47), which was adapted to the reality of the present study. A hypothetical cohort of patients in ambulatory care setting was simulated considering the perspective of the Brazilian public health system. Direct costs related to health care were obtained from the national databases, and the probability of occurrence of DRMs was established by a panel of clinical experts. Sensitivity analyses were conducted. RESULTS: An estimated 59% ± 14% of all patients assisted by the health system suffer some DRMs. Given these cases, 53% ± 18% were considered preventable. The average cost of managing a patient with any DRM was US $155. The cost of illness of the DRMs in Brazil would account for nearly US $18 billion (US $9-$27 billion) (best and worst case scenarium) annually. This amount is 5 times higher than what the Ministry of Health spends to guarantee free medicines in Brazil. Hospitalizations and long-term stays in hospital correspond to 75% of this cost. The sensitivity analysis showed that the model is sensitive to variations in these two outcomes. CONCLUSIONS: According to the model, a large proportion of patients experience DRM and the economic impact to solve these problems is substantial for the health system. Considering that more than half of these cases are preventable, it could be possible to achieve an enormous saving of resources through actions that improve the process of medication use.

Comorbidities, potentially dangerous and low therapeutic index medications: factors linked to emergency visits.

This article aims to investigate the morbidities related to medications, their risk factors and causes detected in patients who seek the Hospital Emergency Service of a University in the South of Brazil. Data collection was based on application of a questionnaire to patients of a minimum age of 18 years, that signing the Term of Free and Informed Consent (TFIC), during the period from October 2013 to March 2014, and analysis of electronic record charts. Cases were evaluated by pharmacists and a doctor to define whether it was a case of medication related morbidity (MRM) and to establish its possible causes. Avoidability of MRM was verified based on criteria previously established in the literature. In total 535 patients were interviewed, and the frequency of MRM was 14.6%, Approximately 45% of MRMs were related to safety in the use of medications, and approximately 50% presented user-related questions as the possible cause. Hospitalization was required in 44.8% of MRM cases; 62.7% of cases were considered avoidable. Presence of chronic disease and use of potentially dangerous medication and low therapeutic index were considered independent factors associated with development of MRM, according to statistical analysis.

Comorbidities, potentially dangerous and low therapeutic index medications: factors linked to emergency visits / Comorbidades, medicamentos potencialmente perigosos e de baixo índice terapêutico: fatores associados à busca da emergência hospitalar

Abstract This article aims to investigate the morbidities related to medications, their risk factors and causes detected in patients who seek the Hospital Emergency Service of a University in the South of Brazil. Data collection was based on application of a questionnaire to patients of a minimum age of 18 years, that signing the Term of Free and Informed Consent (TFIC), during the period from October 2013 to March 2014, and analysis of electronic record charts. Cases were evaluated by pharmacists and a doctor to define whether it was a case of medication related morbidity (MRM) and to establish its possible causes. Avoidability of MRM was verified based on criteria previously established in the literature. In total 535 patients were interviewed, and the frequency of MRM was 14.6%, Approximately 45% of MRMs were related to safety in the use of medications, and approximately 50% presented user-related questions as the possible cause. Hospitalization was required in 44.8% of MRM cases; 62.7% of cases were considered avoidable. Presence of chronic disease and use of potentially dangerous medication and low therapeutic index were considered independent factors associated with development of MRM, according to statistical analysis.

Resumo O objetivo deste artigo é investigar as morbidades relacionadas a medicamentos (MRM), os fatores e as causas detectados em pacientes que buscam o serviço de emergência de hospital universitário do sul do Brasil. A coleta de dados baseou-se na aplicação de um questionário aos pacientes com idade mínima de 18 anos, durante o período de outubro de 2013 a março de 2014, e na análise do prontuário eletrônico. Os casos foram avaliados para definir se era um caso de MRM e para estabelecer as suas possíveis causas. A evitabilidade da MRM foi verificada com base em critérios previamente estabelecidos na literatura. No total foram entrevistados 535 pacientes e a frequência de MRM foi de 14,6%. Aproximadamente, 45% das MRMs foram relacionadas com a segurança no uso de medicamentos e cerca de 50% apresentou como possível causa questões relacionadas ao usuário. Houve necessidade de internação em 44,8% dos casos de MRM; 62,7% dos casos foram considerados evitáveis. Presença de doença crônica e utilização de medicamentos potencialmente perigosos e de baixo índice terapêutico foram consideradas fatores associados ao desenvolvimento de MRM.

Efficacious Cefazolin Prophylactic Dose for Morbidly Obese Women Undergoing Bariatric Surgery Based on Evidence from Subcutaneous Microdialysis and Populational Pharmacokinetic Modeling.

PURPOSE: To determine the efficacious cefazolin prophylactic dose for bariatric surgery using free subcutaneous concentrations accessed by microdialysis after 2 g or 3 g i.v. bolus dosing to morbidly obese women and POPPK modeling. METHODS: A POPPK model with variable plasma and subcutaneous tissue protein binding was developed to simultaneously describe plasma and tissue data sets. The outcomes was predicted for common surgical site infection (SSI) bacteria over 3, 4, 5 and 6 h periods postdose, as probability of target attainment (PTA) using Monte Carlo simulation. RESULTS: CFZ 2 g warrant up to 5 h SSI prophylaxis for bacteria with MICs ≤1 mg/L such as Escherichia coli and Staphylococcus aureus. For species such as Klebsiella pneumoniae, which present MIC distribution frequency of 2 mg/L, the maintenance of PTA ≥ 90% occurs with a 3 g dose for surgeries lasting up to 5 h, and 2 g dose provide an adequate response up to 4 h (PTA of 89%). CONCLUSIONS: Effectiveness of CFZ 2 g is similar to 3 g against bacteria with a MIC up to 2 mg/L, especially if the surgery does not last for more than 4 h.