Custo-utilidade da utilização de teste farmacogenético como guia para o tratamento de depressão sob a perspectiva do Sistema de Saúde Suplementar / Cost-utility of pharmacogenetic testing as a guide for the treatment of depression from the Brazilian Supplementary Health System perspective

Objetivo: Desenvolver uma análise de custo-utilidade da implementação do teste farmacogenético como uma ferramenta adicional para orientar a escolha do melhor tratamento medicamentoso para indivíduos com depressão. Métodos: Para a realização desta análise, criou-se um modelo analítico de decisão baseado em um modelo de Markov. A avaliação foi realizada sob a perspectiva do Sistema de Saúde Suplementar brasileiro, com horizonte temporal de 10 anos, incluindo custos médicos diretos e custos da tecnologia utilizada, além de ter como comparador o tratamento empírico tradicional para a depressão. As probabilidades de transição foram obtidas por meio de análise da literatura disponível. Também foram realizadas análises de sensibilidade probabilística e univariada. Adicionalmente, foi realizada uma avaliação sob a perspectiva da sociedade, incluindo os custos de tratamento medicamentoso realizados pelos pacientes. Resultados: De acordo com a análise realizada, o emprego do teste farmacogenético como guia do tratamento para depressão mostrou-se favorável, proporcionando economia de -R$ 3.439,97 por paciente e aumento de 0,39 QALY ao longo do horizonte temporal. Assim, evidencia-se uma economia significativa a favor do teste farmacogenético, correspondendo a -R$ 8.776,78 por QALY salvo. Além disso, a robustez do modelo foi comprovada por meio das análises de sensibilidade. No cenário sob perspectiva da sociedade, o resultado foi ainda mais favorável, proporcionando economia de -R$ 9.381,49 por paciente e aumento de 0,39 QALY, correspondendo a -R$ 23.936,05 por QALY salvo. Conclusão: Os resultados encontrados neste estudo demonstraram que o uso de testes farmacogenéticos no tratamento da depressão é economicamente vantajoso, com aumento no valor de QALY e redução nos custos médicos diretos, em comparação ao tratamento empírico tradicional. Essa descoberta alinha-se à tendência atual de personalização no cuidado da saúde mental, sugerindo implicações práticas na reavaliação de protocolos, com potencial incorporação dos testes farmacogenéticos como padrão de cuidado.

Objective: To evaluate the cost-utility of pharmacogenetic testing incorporation as an additional tool in guiding the selection of optimal drug treatments for individuals with depression. Methods: A decision analytical model was created based on the Markov model for this analysis. The evaluation was conducted from the perspective of the Brazilian Supplementary Health System, with a time horizon of 10 years. The study included direct medical and technology costs and a comparison with traditional empirical treatment for depression was performed. Transition probabilities were derived from an analysis of available literature. Probabilistic and univariate sensitivity analyses were also carried out. Additionally, an evaluation was conducted from the perspective of Society, including the costs of drug treatment carried out by patients. Results: The application of pharmacogenetic testing as a guide for depression treatment demonstrated favorable outcomes, yielding savings of -R$ 3,439.97 per patient and an increase of 0.39 QALY over the specified time frame. Thus, significant savings were evident, corresponding to -R$ 8,776.78 per QALY saved. The sensitivity analyses confirmed the model's robustness. In the Society's perspective scenario, the outcome was even more favorable, resulting in savings of -R$ 9,381.49 per patient and a 0.39 increase in QALYs, equivalent to -R$ 23,936.05 per QALY saved. Conclusion: The study findings reveal that incorporating harmacogenetic tests in depression treatment offers economic benefits, evidenced by an increase in QALY value and a decrease in direct medical costs compared to conventional empirical treatment. This aligns with the ongoing trend towards personalized mental health care, implying practical considerations for protocol reassessment and the possible integration of pharmacogenetic tests as a standard of care.

Evaluation methods and application progress of drug cytotoxicity in vitro / 中国基层医药

Drugs have both therapeutic and toxic side effects. How to quickly determine the toxicity of the test substance is very important for drug development. In vitro cytotoxicity testing compensates for the shortcomings of using animal models for toxicity evaluation. Its role in toxicity evaluation is increasingly important. The development of computer technology and in-depth research in proteomics, genomics, and metabolomics provide a method for in vitro cytotoxicity evaluation towards a faster and more accurate direction. This paper reviews the commonly used cells, evaluation indicators, and detection techniques for in vitro cytotoxicity evaluation, in order to provide some reference for related research.

Susceptibility to thiopurine toxicity by TPMT and NUDT15 variants in Colombian children with acute lymphoblastic leukemia / Asociación de variantes genéticas en TPMT y NUDT15 con los eventos de toxicidad durante la terapia de mantenimiento en niños colombianos con Leucemia Linfoide Aguda

Abstract Objective: This study aimed to correlate the genetic profile of the NUDT15 and TPMT genes with the side effects of the treatment of pediatric patients with acute lymphoid leukemia who were undergoing maintenance therapy at a tertiary care hospital in 2017. Methods: This was an analytical, longitudinal, observational study in which the genotypes of the genes of interest were determined by PCR allelic discrimination with TaqMan® probes in patients receiving chemotherapy during the maintenance phase in the Pediatric Hematology and Oncology Unit in 2017. Sociodemographic and clinical data corresponding to the first six months of their maintenance chemotherapy were collected, and the correlation between the genotypes obtained and the development of side effects during the maintenance phase of chemotherapy in these patients was evaluated. Results: Seventy pediatric patients were included in the study. Genetic analyses were carried out of these for NUDT15 and TPMT (rs1800462 and rs1800460) on 68 patients, while for the rs1142345 polymorphism, typing was achieved in 42 patients. 4/68 patients were heterozygous for NUDT15, and the same number of patients were heterozygous for rs1800462 and rs1142345, while for rs1800460, 6 heterozygous patients were identified. No statistically significant association was identified between the genetic variants and the outcomes of interest. Conclusion: Studies with a larger population size are needed and the evaluation of other genetic variants that may influence the development of side effects during maintenance chemotherapy.

Resumen Objetivo: la finalidad de este estudio fue evaluar las asociaciones entre los perfiles de los genes NUDT15 y TPMT con los efectos adversos del tratamiento de mantenimiento en pacientes pediátricos con Leucemia Linfoblástica Aguda atendidos en un hospital de referencia durante el 2017. Métodos: Este fue un estudio observacional analítico, de corte longitudinal en el que los genotipos de los genes de interés fueron determinados mediante PCR de discriminación alélica con sondas TaqMan® en pacientes que estaban recibiendo quimioterapia de mantenimiento en la Unidad de Oncohematología Pediátrica durante el 2017. Los datos clínicos y sociodemográficos correspondientes a los primeros 6 meses de sus tratamientos de mantenimiento fueron colectados, y se evaluó la correlación entre los genotipos identificados y el desarrollo de efectos secundarios en estos pacientes. Resultados: setenta pacientes fueron incluidos en el estudio, de estos, los análisis genéticos para NUDT15 y TPMT (rs1800462 and rs1800460) fueron realizados en 68 pacientes, en tanto que para el polimorfismo rs1142345 se logró la tipificación en 42 pacientes. 4/68 pacientes fueron heterocigotos para NUDT15 y el mismo número de pacientes fueron heterocigotos para rs1800462 and rs1142345, mientras que para rs1800460, 6 pacientes heterocigotos fueron identificados. No se identificaron asociaciones estadísticamente significantes entre las variants genéticas y los resultados clínicos de interés. Conclusiones: Estos hallazgos resaltan la importancia de realizar estudios de este tipo con un mayor número de sujetos de estudio, así como plantean la necesidad de evaluar otras variantes genéticas que podrían tener algún impacto en el desarrollo de efectos secundarios durante la quimioterapia de mantenimiento.