Reactions related to asparaginase infusion in a 10-year retrospective cohort

Abstract Introduction: Although it is an essential component of the treatment of acute lymphoid leukemia in children, asparaginase causes adverse reactions that sometimes make it impossible to use it fully. Hypersensitivity reactions are the most frequent and may lead to early discontinuation of treatment. The present study aimed to investigate suspicions of adverse reactions during the infusion of asparaginase in a pediatric cohort. Methods: A retrospective observational study was carried out at a university pediatric institute in the state of Rio de Janeiro. Information regarding clinical features and characteristics of adverse reactions was collected from hospital medical records. Suspicions of adverse reactions were classified regarding causality and severity. Results: Seventy-three suspicions of adverse reactions were recorded during asparaginase infusion in 72 children in the study period. Allergic hypersensitivity reactions were suspected in 60.5% of the cases. Of these, 25% of the reactions occurred during induction and 61.1% in concomitant use with vincristine, findings that diverge from other studies. High-risk classification and younger age were considered risk factors for these reactions. A total of 72.4% of the reactions were classified as grade 1 or 2, which suggest that not all are related to antibody formation; this highlights the importance of differential diagnosis with other reactions, such as non-allergic hypersensitivity and hyperammonemia. Conclusion: The implementation of the differential diagnosis of reactions related to infusion of asparaginase with ammonia dosage and classification of the grade of reactions is crucial to facilitate the identification and proper management of each type of reaction.

Reactions related to asparaginase infusion in a 10-year retrospective cohort.

INTRODUCTION: Although it is an essential component of the treatment of acute lymphoid leukemia in children, asparaginase causes adverse reactions that sometimes make it impossible to use it fully. Hypersensitivity reactions are the most frequent and may lead to early discontinuation of treatment. The present study aimed to investigate suspicions of adverse reactions during the infusion of asparaginase in a pediatric cohort. METHODS: A retrospective observational study was carried out at a university pediatric institute in the state of Rio de Janeiro. Information regarding clinical features and characteristics of adverse reactions was collected from hospital medical records. Suspicions of adverse reactions were classified regarding causality and severity. RESULTS: Seventy-three suspicions of adverse reactions were recorded during asparaginase infusion in 72 children in the study period. Allergic hypersensitivity reactions were suspected in 60.5% of the cases. Of these, 25% of the reactions occurred during induction and 61.1% in concomitant use with vincristine, findings that diverge from other studies. High-risk classification and younger age were considered risk factors for these reactions. A total of 72.4% of the reactions were classified as grade 1 or 2, which suggest that not all are related to antibody formation; this highlights the importance of differential diagnosis with other reactions, such as non-allergic hypersensitivity and hyperammonemia. CONCLUSION: The implementation of the differential diagnosis of reactions related to infusion of asparaginase with ammonia dosage and classification of the grade of reactions is crucial to facilitate the identification and proper management of each type of reaction.

Use of pharmacy records to measure treatment adherence: a critical review of the literature. / Utilização de registros de dispensação de medicamentos na mensuração da adesão: revisão crítica da literatura.

The current frame of reference on adherence to pharmacotherapy includes a set of behaviors experienced by the user, with observation of the detailed and continuous history of the use of each dose of the medication. Indicators based on pharmacy records have been used to measure adherence. The current review aimed to identify and describe indicators based on pharmacy records and to discuss their adequacy and limitations for measuring adherence. An exploratory literature review was conducted in three databases using the terms "adherence", "pharmacy records/administrative data", and "measure" to compose the descriptors for the selection of 81 articles and the elaboration of a chart with the denomination, sources, methods for calculation, description, and interpretation of the operational and referential meaning of 14 indicators. Given the most recent taxonomy for adherence proposed in the literature, we concluded that the indicators can be useful for identifying patients with medication-seeking behavior-related problems and analysis of persistence. The distance between supply-related events and difficulties in treatment follow-up can influence an analysis based exclusively on the use of these indicators.

Utilização de registros de dispensação de medicamentos na mensuração da adesão: revisão crítica da literatura / Uso de registros de farmacia para medir la adherencia al tratamiento: una revisión crítica de la literatura / Use of pharmacy records to measure treatment adherence: a critical review of the literature

Resumo: O marco atual sobre a adesão à farmacoterapia compreende um conjunto de comportamentos experimentados pelo usuário em que se observa a trajetória detalhada e contínua do uso de cada dose do medicamento. Indicadores provenientes de registros de dispensação de medicamentos têm sido utilizados para a mensuração da adesão. A presente revisão visou a identificar e a caracterizar indicadores provenientes de registros de dispensação e a discutir sua adequação e limitações para mensuração da adesão. Foi realizada uma busca bibliográfica exploratória em três bases de dados a partir dos termos "adesão", "registros de farmácia/dados administrativos" e "medida" na composição dos descritores para a seleção de 81 artigos e elaboração de um quadro com a denominação, fontes, método de cálculo, descrição e interpretação do significado operacional e referencial de 14 indicadores. Tendo em vista a mais recente taxonomia da adesão proposta na literatura, concluiu-se que os indicadores encontrados podem ser úteis na identificação de pacientes com problemas relacionados ao comportamento de busca de medicamentos e na análise da persistência. A distância entre os eventos relacionados ao fornecimento e as dificuldades no seguimento da terapêutica podem influenciar a análise baseada exclusivamente no uso desses indicadores.

Resumen: El marco de referencia actual sobre la adherencia a la farmacoterapia incluye un conjunto de comportamientos experimentados por el usuario, con observación de la historia detallada y continua del uso de cada dosis de la medicación. Se han utilizado indicadores basados en registros de farmacia para medir la adherencia. La revisión actual tuvo como objetivo identificar y describir indicadores basados en registros de farmacia y discutir su adecuación y limitaciones para medir la adherencia. Se realizó una revisión exploratoria de la literatura en tres bases de datos utilizando los términos "adherencia", "registros de farmacia/datos administrativos" y "medida" para componer los descriptores para la selección de 81 artículos y la elaboración de un cuadro con la denominación, métodos de cálculo, descripción e interpretación del significado operacional y referencial de 14 indicadores. Dada la taxonomía más reciente para la adherencia propuesta en la literatura, concluimos que los indicadores pueden ser útiles para identificar pacientes con problemas relacionados con el comportamiento de búsqueda de medicamentos y el análisis de la persistencia. La distancia entre los eventos relacionados con la oferta y las dificultades en el seguimiento del tratamiento puede influir en un análisis basado exclusivamente en el uso de estos indicadores.

Abstract: The current frame of reference on adherence to pharmacotherapy includes a set of behaviors experienced by the user, with observation of the detailed and continuous history of the use of each dose of the medication. Indicators based on pharmacy records have been used to measure adherence. The current review aimed to identify and describe indicators based on pharmacy records and to discuss their adequacy and limitations for measuring adherence. An exploratory literature review was conducted in three databases using the terms "adherence", "pharmacy records/administrative data", and "measure" to compose the descriptors for the selection of 81 articles and the elaboration of a chart with the denomination, sources, methods for calculation, description, and interpretation of the operational and referential meaning of 14 indicators. Given the most recent taxonomy for adherence proposed in the literature, we concluded that the indicators can be useful for identifying patients with medication-seeking behavior-related problems and analysis of persistence. The distance between supply-related events and difficulties in treatment follow-up can influence an analysis based exclusively on the use of these indicators.

The medicine selection process in four large university hospitals in Brazil: Does the DTC have a role?

Knowledge about evidence-based medicine selection and the role of the Drug and Therapeutics Committee (DTC) is an important topic in the literature but is scarcely discussed in Brazil. Our objective, using a qualitative design, was to analyze the medicine selection process performed in four large university hospitals in the state of Rio de Janeiro. Information was collected from documents, interviews with key informants and direct observations. Two dimensions were analyzed: the structural and organizational aspects of the selection process and the criteria and methods used in medicine selection. The findings showed that the DTC was active in two hospitals. The structure for decision-making was weak. DTC members had little experience in evidence-based selection, and their everyday functions did not influence their participation in DTC activities. The methods used to evaluate evidence were inadequate. The uncritical adoption of new medicines in these complex hospital facilities may be hampering pharmaceutical services, with consequences for the entire health system. Although the qualitative approach considerably limits the extent to which the results can be extrapolated, we believe that our findings may be relevant to other university hospitals in the country.

A produção de conhecimento sobre a seleção de medicamentos baseada em evidências e executada por Comissões de Farmácia e Terapêutica é ainda escassa no Brasil, apesar da ampla discussão sobre o tema em países desenvolvidos. Este estudo buscou conhecer e analisar os aspectos relacionados à seleção de medicamentos em quatro hospitais universitários de grande porte no Rio de Janeiro, por meio de abordagem qualitativa. Entrevistas, observação direta e análise documental instrumentaram a coleta de dados qualitativos e quantitativos. A análise considerou duas dimensões: (i) estrutura e organização para o processo de seleção e (ii) critérios e métodos utilizados para avaliação. Apenas dois hospitais possuíam Comissão de Farmácia e Terapêutica (CFT) ativa. A estrutura para a tomada de decisão era deficiente e os membros das Comissões apontaram pouca experiência e disponibilidade para a atividade. Os métodos de avaliação e critérios observados indicaram um processo de seleção acrítico nestes hospitais, comprometendo a assistência farmacêutica e potencialmente prejudicando o sistema de saúde. Apesar da metodologia qualitativa não permitir a extrapolação de resultados, é possível que este cenário seja parecido com o de outros hospitais universitários brasileiros.

An analytical framework for assessing drug and therapeutics committee structure and work processes in tertiary Brazilian hospitals.

University teaching hospitals usually provide tertiary care and are subject to early adoption of new technologies, which may compromise healthcare systems when uncritically adopted. Knowledge on the decision-making process - drug selection by drug selection committees or DTCs - is crucial to improve the quality of care. There are no models for studying the selection of drugs in Brazilian healthcare services. This study aims to discuss DTC structure and the processes regarding adoption of medicines in tertiary university hospitals in Brazil and to propose an analytical structure for providing direction for the future. State of the art content regarding drug selection processes and DTC procedures was reviewed in three databases. Information on the medicine selection process in a Brazilian gold standard teaching hospital was collected through observations and a review of existing procedures. A structured discussion on medicine selection and DTC procedures in tertiary hospitals ensued. This discussion resulted in findings that were organized in three dimensions, composing an analytical framework for the application in tertiary Brazilian hospitals (i) motivations for the adoption of drugs; (ii) necessary structural and organizational aspects for decision-making; and (iii) criteria and methods employed by the decision-making process. We believe that the suggested framework is compatible with tertiary Brazilian hospitals, because a gold standard in the country was able to conduct all its procedures in the light of WHO and international recommendations. We hope to contribute in producing knowledge which may hopefully be adopted in tertiary hospitals across Brazil.

[Dispensing specialized component medicines in areas of the State of Rio de Janeiro]. / Dispensação de medicamentos do componente especializado em polos no Estado do Rio de Janeiro.

The Specialized Pharmaceutical Services Component (CEAF) ensures the dispensing of high-cost medicines for the treatment of specific diseases. The fact that these medicines are mandatory though access is only through legal injunctions, suggests flaws in the management of pharmaceutical services. This paper analyzed adherence to Clinical Protocols and Therapeutic Guidelines (PCDT) in the dispensing of these CEAF medicines. Qualitative research was also conducted in facilities with different characteristics in the State of Rio de Janeiro. It was noted that the lack of adequate structure in the units studied, including trained personnel, compromises the dispensing CEAF medicines in all facilities. The CEAF dispensing procedure, heavily dependent on interaction between prescribers and dispensers, is not carried out as would be expected. It is possible that inadequate performance is also linked to flaws in the planning and organization of services. The results indicate barriers in adherence to PCDT by health professionals, prejudicing health system users and possibly leading them to access medicines by legal means. It is believed that characteristics of the investigated facilities are similar to others in Brazil, and the barriers identified may be the same, compromising healthcare.

Dispensação de medicamentos do componente especializado em polos no Estado do Rio de Janeiro / Dispensing specialized component medicines in areas of the State of Rio de Janeiro

O Componente Especializado da Assistência Farmacêutica (CEAF) deve garantir dispensação de medicamentos de alto custo para o tratamento de doenças específicas. O fato desses medicamentos, previstos em listas oficiais, serem pleiteados por via judicial como estratégia de acesso à farmacoterapia sugere falhas na gestão da assistência. O presente estudo analisou a adesão aos Protocolos Clínicas e Diretrizes Terapêuticas (PCDT) no processo de dispensação de medicamentos do CEAF. Foi realizada uma pesquisa qualitativa em farmácias ambulatoriais de diferentes características no estado do Rio de Janeiro. Observou-se que a estrutura das unidades estudadas compromete a dispensação dos medicamentos do CEAF, havendo falta de recursos humanos capacitados. O fluxo de dispensação, fortemente dependente da interação entre prescritores e dispensadores, não é realizado como seria esperado. É possível que as fragilidades no desempenho das atividades tenham origem em falhas no planejamento e na organização de serviços. Os resultados indicam barreiras na adesão dos profissionais aos PCDT, prejudicando os usuários e podendo fomentar a busca da via judicial. Estima-se que as unidades investigadas sejam semelhantes a outras no país, e que as barreiras observadas se reproduzam, comprometendo a assistência.

The Specialized Pharmaceutical Services Component (CEAF) ensures the dispensing of high-cost medicines for the treatment of specific diseases. The fact that these medicines are mandatory though access is only through legal injunctions, suggests flaws in the management of pharmaceutical services. This paper analyzed adherence to Clinical Protocols and Therapeutic Guidelines (PCDT) in the dispensing of these CEAF medicines. Qualitative research was also conducted in facilities with different characteristics in the State of Rio de Janeiro. It was noted that the lack of adequate structure in the units studied, including trained personnel, compromises the dispensing CEAF medicines in all facilities. The CEAF dispensing procedure, heavily dependent on interaction between prescribers and dispensers, is not carried out as would be expected. It is possible that inadequate performance is also linked to flaws in the planning and organization of services. The results indicate barriers in adherence to PCDT by health professionals, prejudicing health system users and possibly leading them to access medicines by legal means. It is believed that characteristics of the investigated facilities are similar to others in Brazil, and the barriers identified may be the same, compromising healthcare.