Isoniazid use, effectiveness, and safety for treatment of latent tuberculosis infection: a systematic review.

BACKGROUND: The treatment strategy for latent tuberculosis infection is to reduce the number of tuberculosis cases and consequently reduce the transmission of pathogenic bacteria. This study aimed to determine the safety, effectiveness, and adherence of isoniazid use for latent tuberculosis infection treatment. METHODS: To identify studies on isoniazid use for latent tuberculosis infection, five electronic databases were searched. The methods and results are presented in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Most studies (53) used isoniazid for 9 months. The prevalence of use and adherence to treatment varied considerably (18% to 100%), and were evaluated by participant completion of isoniazid treatment for latent tuberculosis infection. The adverse events most frequently reported were hepatotoxicity, gastric intolerance, and neuropathy; the rates of occurrence ranged from < 1% to 48%. In the studies that evaluated the effectiveness of isoniazid for latent tuberculosis infection, the rate varied from 0 to 19.7% for patients who did not have active tuberculosis after the follow-up period. CONCLUSIONS: The importance of maintaining follow up for patients using isoniazid should be emphasized due to the risk of developing adverse events. Despite the treatment challenges, the rates of patients who used isoniazid and developed active tuberculosis during the follow-up period were low. We believe that isoniazid continues to contribute to tuberculosis control worldwide, and better care strategies are required.

Prevalence of trachoma in indigenous and non-indigenous areas, Northeastern Brazil, 2019–2021 / Prevalencia del tracoma en zonas de población indígena y no indígena del nordeste de Brasil, 2019-2021 / Prevalência de tracoma em áreas indígenas e não indígenas, Nordeste do Brasil, 2019-2021

[ABSTRACT]. Objective. To estimate the prevalence of trachoma in indigenous and non-indigenous populations in selected areas of the state of Maranhão, in northeastern Brazil. Methods. This was a population-based survey with probabilistic sampling. For the diagnosis of trachoma, external ocular examination was performed using head magnifying loupes, at 2.5X magnification. The prevalence of trachomatous inflammation – follicular (TF) in children aged 1–9 years and the prevalence of trachomatous trichiasis (TT) in the population aged ≥15 years were estimated. Relative frequencies of sociodemographic and environmental characteristics were obtained. Results. The study included 7 971 individuals, 3 429 from non-indigenous populations and 4 542 from indigenous populations. The prevalence of TF in non-indigenous and indigenous populations was 0.1% and 2.9%, respectively, and the prevalence of TT among indigenous populations was 0.1%. Conclusions. The prevalence of TF and TT in the two evaluation units in the state of Maranhão were within the limits recommended for the elimination of trachoma as a public health problem. However, the prevalence of TF was higher in the indigenous evaluation unit, indicating a greater vulnerability of this population to the disease. The prevalence of TF of below 5.0% implies a reduction in transmission, which may have resulted from improved socioeconomic conditions and/or the implementation of the World Health Organization SAFE strategy.

[RESUMEN]. Objetivo. Estimar la prevalencia del tracoma en poblaciones indígenas y no indígenas en determinadas zonas del estado de Maranhão, en el nordeste de Brasil. Métodos. Se trató de una encuesta de ámbito poblacional con muestreo probabilístico. Para el diagnóstico del tracoma, se realizó un examen ocular externo con una lupa frontal de 2,5X aumentos. Se estimó la prevalencia de la inflamación tracomatosa folicular (TF) en la población infantil de 1 a 9 años y la prevalencia de la triquiasis tracomatosa (TT) en la población de 15 años o más. Se obtuvieron las frecuencias relativas de las características sociodemográficas y ambientales. Resultados. En el estudio participaron 7 971 personas, 3 429 de poblaciones no indígenas y 4 542 de poblaciones indígenas. La prevalencia de la TF en las poblaciones no indígenas e indígenas fue de 0,1% y 2,9%, respectivamente, en tanto que la de la TT en las poblaciones indígenas fue de 0,1%. Conclusiones. La prevalencia de la TF y la TT en las dos unidades de evaluación del estado de Maranhão estuvo dentro de los límites recomendados para la eliminación del tracoma como problema de salud pública. Sin embargo, la prevalencia de la TF fue mayor en la unidad de evaluación indígena, lo que indica una mayor vulnerabilidad de esta población a la enfermedad. La prevalencia de la TF inferior al 5,0% implica una reducción de la transmisión, que puede haber sido consecuencia tanto de la mejora de las condiciones socioeconómicas como de la aplicación de la estrategia SAFE de la Organización Mundial de la Salud.

[RESUMO]. Objetivo. Estimar a prevalência do tracoma em populações indígenas e não indígenas em áreas selecionadas do estado do Maranhão, na região Nordeste do Brasil. Métodos. Inquérito de base populacional com amostragem probabilística. Para o diagnóstico de tracoma, foi realizado exame ocular externo com o auxílio de lupas binoculares com ampliação de 2,5×. Foram estimadas a prevalência de inflamação tracomatosa folicular (TF) em crianças de 1 a 9 anos de idade e a prevalência de triquíase tracomatosa (TT) na população com idade ≥15 anos. Foram obtidas as frequências relativas das características sociodemográficas e ambientais. Resultados. O estudo incluiu 7 971 indivíduos (3 429 de populações não indígenas e 4 542 de populações indígenas). A prevalência de TF nas populações não indígenas e indígenas foi de 0,1% e 2,9%, respectiva- mente, e a prevalência de TT entre as populações indígenas foi de 0,1%. Conclusões. A prevalência de TF e TT nas duas unidades de avaliação no estado do Maranhão ficou dentro dos limites recomendados para a eliminação do tracoma como problema de saúde pública. No entanto, a prevalência de TF foi maior na unidade de avaliação indígena, indicando uma maior vulnerabilidade dessa população à doença. A prevalência de TF abaixo de 5,0% implica uma redução na transmissão, que pode ter sido resultado de melhores condições socioeconômicas e da implementação da estratégia SAFE da Organização Mundial da Saúde.

Prevalence of trachoma in indigenous and non-indigenous areas, Northeastern Brazil, 2019-2021.

Objective: To estimate the prevalence of trachoma in indigenous and non-indigenous populations in selected areas of the state of Maranhão, in northeastern Brazil. Methods: This was a population-based survey with probabilistic sampling. For the diagnosis of trachoma, external ocular examination was performed using head magnifying loupes, at 2.5X magnification. The prevalence of trachomatous inflammation - follicular (TF) in children aged 1-9 years and the prevalence of trachomatous trichiasis (TT) in the population aged ≥15 years were estimated. Relative frequencies of sociodemographic and environmental characteristics were obtained. Results: The study included 7 971 individuals, 3 429 from non-indigenous populations and 4 542 from indigenous populations. The prevalence of TF in non-indigenous and indigenous populations was 0.1% and 2.9%, respectively, and the prevalence of TT among indigenous populations was 0.1%. Conclusions: The prevalence of TF and TT in the two evaluation units in the state of Maranhão were within the limits recommended for the elimination of trachoma as a public health problem. However, the prevalence of TF was higher in the indigenous evaluation unit, indicating a greater vulnerability of this population to the disease. The prevalence of TF of below 5.0% implies a reduction in transmission, which may have resulted from improved socioeconomic conditions and/or the implementation of the World Health Organization SAFE strategy.

Isoniazid use, effectiveness, and safety for treatment of latent tuberculosis infection: a systematic review

ABSTRACT Background: The treatment strategy for latent tuberculosis infection is to reduce the number of tuberculosis cases and consequently reduce the transmission of pathogenic bacteria. This study aimed to determine the safety, effectiveness, and adherence of isoniazid use for latent tuberculosis infection treatment. Methods: To identify studies on isoniazid use for latent tuberculosis infection, five electronic databases were searched. The methods and results are presented in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Most studies (53) used isoniazid for 9 months. The prevalence of use and adherence to treatment varied considerably (18% to 100%), and were evaluated by participant completion of isoniazid treatment for latent tuberculosis infection. The adverse events most frequently reported were hepatotoxicity, gastric intolerance, and neuropathy; the rates of occurrence ranged from < 1% to 48%. In the studies that evaluated the effectiveness of isoniazid for latent tuberculosis infection, the rate varied from 0 to 19.7% for patients who did not have active tuberculosis after the follow-up period. Conclusions: The importance of maintaining follow up for patients using isoniazid should be emphasized due to the risk of developing adverse events. Despite the treatment challenges, the rates of patients who used isoniazid and developed active tuberculosis during the follow-up period were low. We believe that isoniazid continues to contribute to tuberculosis control worldwide, and better care strategies are required.

Prevalence of trachoma in indigenous and non-indigenous areas, Northeastern Brazil, 2019-2021 / Prevalencia del tracoma en zonas de población indígena y no indígena del nordeste de Brasil, 2019-2021 / Prevalência de tracoma em áreas indígenas e não indígenas, Nordeste do Brasil, 2019-2021

ABSTRACT Objective. To estimate the prevalence of trachoma in indigenous and non-indigenous populations in selected areas of the state of Maranhão, in northeastern Brazil. Methods. This was a population-based survey with probabilistic sampling. For the diagnosis of trachoma, external ocular examination was performed using head magnifying loupes, at 2.5X magnification. The prevalence of trachomatous inflammation - follicular (TF) in children aged 1-9 years and the prevalence of trachomatous trichiasis (TT) in the population aged ≥15 years were estimated. Relative frequencies of sociodemographic and environmental characteristics were obtained. Results. The study included 7 971 individuals, 3 429 from non-indigenous populations and 4 542 from indigenous populations. The prevalence of TF in non-indigenous and indigenous populations was 0.1% and 2.9%, respectively, and the prevalence of TT among indigenous populations was 0.1%. Conclusions. The prevalence of TF and TT in the two evaluation units in the state of Maranhão were within the limits recommended for the elimination of trachoma as a public health problem. However, the prevalence of TF was higher in the indigenous evaluation unit, indicating a greater vulnerability of this population to the disease. The prevalence of TF of below 5.0% implies a reduction in transmission, which may have resulted from improved socioeconomic conditions and/or the implementation of the World Health Organization SAFE strategy.

RESUMEN Objetivo. Estimar la prevalencia del tracoma en poblaciones indígenas y no indígenas en determinadas zonas del estado de Maranhão, en el nordeste de Brasil. Métodos. Se trató de una encuesta de ámbito poblacional con muestreo probabilístico. Para el diagnóstico del tracoma, se realizó un examen ocular externo con una lupa frontal de 2,5X aumentos. Se estimó la prevalencia de la inflamación tracomatosa folicular (TF) en la población infantil de 1 a 9 años y la prevalencia de la triquiasis tracomatosa (TT) en la población de 15 años o más. Se obtuvieron las frecuencias relativas de las características sociodemográficas y ambientales. Resultados. En el estudio participaron 7 971 personas, 3 429 de poblaciones no indígenas y 4 542 de poblaciones indígenas. La prevalencia de la TF en las poblaciones no indígenas e indígenas fue de 0,1% y 2,9%, respectivamente, en tanto que la de la TT en las poblaciones indígenas fue de 0,1%. Conclusiones. La prevalencia de la TF y la TT en las dos unidades de evaluación del estado de Maranhão estuvo dentro de los límites recomendados para la eliminación del tracoma como problema de salud pública. Sin embargo, la prevalencia de la TF fue mayor en la unidad de evaluación indígena, lo que indica una mayor vulnerabilidad de esta población a la enfermedad. La prevalencia de la TF inferior al 5,0% implica una reducción de la transmisión, que puede haber sido consecuencia tanto de la mejora de las condiciones socioeconómicas como de la aplicación de la estrategia SAFE de la Organización Mundial de la Salud.

RESUMO Objetivo. Estimar a prevalência do tracoma em populações indígenas e não indígenas em áreas selecionadas do estado do Maranhão, na região Nordeste do Brasil. Métodos. Inquérito de base populacional com amostragem probabilística. Para o diagnóstico de tracoma, foi realizado exame ocular externo com o auxílio de lupas binoculares com ampliação de 2,5×. Foram estimadas a prevalência de inflamação tracomatosa folicular (TF) em crianças de 1 a 9 anos de idade e a prevalência de triquíase tracomatosa (TT) na população com idade ≥15 anos. Foram obtidas as frequências relativas das características sociodemográficas e ambientais. Resultados. O estudo incluiu 7 971 indivíduos (3 429 de populações não indígenas e 4 542 de populações indígenas). A prevalência de TF nas populações não indígenas e indígenas foi de 0,1% e 2,9%, respectivamente, e a prevalência de TT entre as populações indígenas foi de 0,1%. Conclusões. A prevalência de TF e TT nas duas unidades de avaliação no estado do Maranhão ficou dentro dos limites recomendados para a eliminação do tracoma como problema de saúde pública. No entanto, a prevalência de TF foi maior na unidade de avaliação indígena, indicando uma maior vulnerabilidade dessa população à doença. A prevalência de TF abaixo de 5,0% implica uma redução na transmissão, que pode ter sido resultado de melhores condições socioeconômicas e da implementação da estratégia SAFE da Organização Mundial da Saúde.

Availability of emergency contraception in large Brazilian municipalities: a guaranteed right?

Introduction: Emergency Contraception (EC) is available in Brazil since 1996, when it was adopted as one if the family planning strategies and, in 1998, for use in services assisting victims of sexual violence. In the country, its use is regulated by guidelines. Its access through SUS (Unified Health System), however, does not seem to occur in a standardized manner. Methods: The aim of the study was to analyze the availability and barriers to accessing emergency contraception (levonorgestrel) in Brazilian municipalities with more than 500 thousand inhabitants. The survey was carried out by a form sent to the Municipal Health Departments (SMS) managers and a search on the list of standardized medicines by the hospitals in the same municipalities. Results: The Basic Health Units were identified as the standard access places to EC. However, one of the obstacles mentioned is the need for a prescription for dispensing in almost 80% of the analyzed cities. Access in emergency situations at night and on weekends is also uncertain, since although 67% of the places stated that they dispense at the hospital level, the item was only standardized in 21% of the hospital lists. Discussion: The difficult access this drug in the public system essentially tends to harm the poorest women, who are the ones who suffer most from the consequences of an unwanted pregnancy.

Overall survival and associated factors in women with metastatic breast cancer treated with trastuzumab at a public referral institution.

OBJECTIVE: To characterize associated factors and overall survival of women with metastatic breast cancer treated with trastuzumab after its incorporation into the SUS, and additionally to present the direct costs of this technology. METHODS: This is a retrospective cohort, based on data from computerized medical records from one of the units of the National Cancer Institute (INCA), in Rio de Janeiro-RJ, Brazil. Women with HER-2 positive metastatic breast cancer undergoing trastuzumab treatment from September 2017 to August 2018 were included. Overall survival was estimated using the Kaplan-Meier method and compared between groups using the log-rank test. RESULTS: 136 women were selected, whose median age at diagnosis was 51 years (range: 21-81 years). The median OS was 43.63 months (95%CI 33.92-53.34). It is observed that the median OS for the population already diagnosed with metastatic disease (stage IV) was significantly lower than for patients diagnosed in stages I-III (37.43 months vs. 48.6 months, p<0, 01). Women without previous use of trastuzumab had a higher median OS than patients pretreated with trastuzumab (45.16 months vs. 40.73 months, p<0.01). CONCLUSION: Trastuzumab improves survival in HER-2 positive metastatic breast cancer. Brain and multiple metastases are associated with a worse prognosis. It is essential to avoid advanced staging and perform surgical treatment, with emphasis on radical mastectomy. The SUS must adopt policies and strategies for early diagnosis and guarantee access to trastuzumab, considering its high cost.

Overall survival and associated factors in women with metastatic breast cancer treated with trastuzumab at a public referral institution / Sobrevida global e fatores associados em mulheres com câncer de mama metastático tratadas com trastuzumabe em uma instituição pública de referência

ABSTRACT Objective: To characterize associated factors and overall survival of women with metastatic breast cancer treated with trastuzumab after its incorporation into the SUS, and additionally to present the direct costs of this technology. Methods: This is a retrospective cohort, based on data from computerized medical records from one of the units of the National Cancer Institute (INCA), in Rio de Janeiro-RJ, Brazil. Women with HER-2 positive metastatic breast cancer undergoing trastuzumab treatment from September 2017 to August 2018 were included. Overall survival was estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Results: 136 women were selected, whose median age at diagnosis was 51 years (range: 21-81 years). The median OS was 43.63 months (95%CI 33.92-53.34). It is observed that the median OS for the population already diagnosed with metastatic disease (stage IV) was significantly lower than for patients diagnosed in stages I-III (37.43 months vs. 48.6 months, p<0, 01). Women without previous use of trastuzumab had a higher median OS than patients pretreated with trastuzumab (45.16 months vs. 40.73 months, p<0.01). Conclusion: Trastuzumab improves survival in HER-2 positive metastatic breast cancer. Brain and multiple metastases are associated with a worse prognosis. It is essential to avoid advanced staging and perform surgical treatment, with emphasis on radical mastectomy. The SUS must adopt policies and strategies for early diagnosis and guarantee access to trastuzumab, considering its high cost.

RESUMO Objetivo: Caracterizar fatores associados e sobrevida global de mulheres com câncer de mama metastático tratadas com trastuzumabe, após sua incorporação ao Sistema Único de Saúde, e apresentar os custos diretos dessa tecnologia. Métodos: Trata-se de uma coorte retrospectiva, baseada em dados de prontuários do Instituto Nacional do Câncer, no Rio de Janeiro (RJ). Foram incluídas mulheres com câncer de mama metastático HER-2 positivo em tratamento com trastuzumabe no período de setembro de 2017 a agosto de 2018. A sobrevida global foi estimada pelo método Kaplan-Meier e comparada entre grupos pelo teste de log-rank. Resultados: Foram selecionadas 136 mulheres, cuja mediana da idade do diagnóstico foi de 51 anos (amplitude: 21-81 anos). A mediana da sobrevida global foi de 43,63 meses (IC95% 33,92-53,34). Observa-se que a mediana da sobrevida global para a população já diagnosticada com doença metastática (estádio IV) foi significativamente menor do que para as pacientes diagnosticadas nos estádios I-III (37,43 meses vs. 48,6 meses, p<0,01). Já mulheres sem uso prévio de trastuzumabe apresentaram uma mediana de sobrevida global maior do que as pacientes pré-tratadas com trastuzumabe (45,16 meses vs. 40,73 meses, p<0,01). Conclusão: O trastuzumabe aumentou a sobrevida no câncer de mama metastático HER-2 positivo. Metástases cerebrais e múltiplas mostraram-se associadas a um pior prognóstico. É fundamental evitar o estadiamento avançado e realizar tratamento cirúrgico, destacando-se a mastectomia radical. O Sistema Único de Saúde deve adotar políticas e estratégias para o diagnóstico precoce e garantir acesso ao trastuzumabe, considerando seu alto custo.

[Social vulnerability, survival, and hospital lethality by COVID-19 in patients aged 50 years and over: retrospective cohort of cases in Brazil in 2020 and 2021]. / Vulnerabilidade social, sobrevida e letalidade hospitalar pela COVID-19 em pacientes com 50 anos ou mais: coorte retrospectiva de casos no Brasil em 2020 e 2021.

The outcome of SARS-CoV-2 infection is not only associated with age and comorbidities but is also aggravated by social vulnerability. This study aims to analyze - according to social vulnerability - survival and hospital lethality by COVID-19 in the first 100 days from symptoms to death in individuals aged 50 years or older hospitalized in Brazil. This is a retrospective cohort from Epidemiological Week 11 of 2020 to week 33 of 2021. The Influenza Epidemiological Surveillance Information System (SIVEP-Gripe) provided clinical and epidemiological data. The Geographic Index of the Socioeconomic Context for Health and Social Studies (GeoSES) measured social vulnerability. The Kaplan-Meier curve and the adjusted proportional risk model by Cox were used for survival, with hazard ratio (HR) and 95% confidence intervals (95%CI). Among the 410,504 cases, overall lethality was of 42.2% in general and 51.4% in the most vulnerable. We found a higher lethality according to worse socioeconomic status in all categories by age group; the double is registered for 50-59 years. The adjusted Cox model showed a 32% increase in risk of death (HR = 1.32; 95%CI: 1.24-1.42). Moreover, men, older adults, black or indigenous adults, with multiple comorbidities, and subjected to invasive ventilation, have a higher risk of death after hospitalization. Intersectoral policy measures need to be targeted to alleviate the effects of the COVID-19 pandemic aggravated by social vulnerability.

O desfecho da infecção pelo SARS-CoV-2 não se associa apenas à idade e a comorbidades, mas também agrava-se por vulnerabilidade social. Este estudo tem como objetivo analisar, segundo vulnerabilidade social, a sobrevida e a letalidade hospitalar por COVID-19 para os primeiros 100 dias entre sintomas até o óbito em indivíduos de 50 anos ou mais hospitalizados no Brasil. Trata-se de uma coorte retrospectiva das Semanas Epidemiológicas 11, de 2020, a 33, de 2021. O Sistema de Informação de Vigilância Epidemiológica da Gripe (SIVEP-Gripe) forneceu dados clínico-epidemiológicos. O Índice Socioeconômico do Contexto Geográfico para Estudos em Saúde (GeoSES) mensurou vulnerabilidade social. Para sobrevida, utilizou-se a curva de Kaplan-Meier e o modelo ajustado de riscos proporcionais de Cox, com hazard ratio (HR) e intervalos de 95% de confiança (IC95%). Dentre os 410.504 casos, a letalidade geral foi de 42,2%, sendo 51,4% os indivíduos mais vulneráveis. Por faixa etária, registra-se a presença de maior letalidade para os piores status socioeconômicos em todas as categorias; para 50-59 anos, registra-se o dobro. O modelo ajustado de Cox mostrou aumento de 32% de risco para óbito (HR = 1,32; IC95%: 1,24-1,42). Ademais, homens, idosos, pretos ou indígenas, com múltiplas comorbidades e submetidos à ventilação invasiva apresentam maior risco de óbito após hospitalização. É necessário que medidas políticas intersetoriais sejam direcionadas para mitigar os efeitos da pandemia de COVID-19 agravados pela vulnerabilidade social.

El pronóstico de la infección por SARS-CoV-2 no sólo está asociado a la edad y a las comorbilidades, sino que también empeora por la vulnerabilidad social. El presente estudio tiene como objetivo analizar, según la vulnerabilidad social, la supervivencia y la letalidad hospitalaria por COVID-19 durante los primeros 100 días entre los síntomas hasta la muerte en individuos de 50 años o más hospitalizados en Brasil. Se trata de una cohorte retrospectiva desde la Semana Epidemiológica 11 de 2020 hasta la 33 de 2021. El Sistema de Información de Vigilancia Epidemiológica de la Gripe (SIVEP-Gripe) proporcionó datos clínico-epidemiológicos. El Índice Socioeconómico del Contexto Geográfico para los Estudios de Salud (GeoSES) midió la vulnerabilidad social. Para la supervivencia se utilizó la curva de Kaplan-Meier y el modelo ajustado de riesgos proporcionales de Cox, con cociente de riesgos (hazard ratio - HR) e intervalos del 95% de confianza (IC95%). Entre los 410.504 casos la letalidad global fue del 42,2%; el 51,4% en los más vulnerables. Por grupos de edad, se registra la presencia de una mayor letalidad a medida que empeora el estatus socioeconómico en todas las categorías; para 50-59 años es el doble. El modelo de Cox ajustado mostró un aumento del 32% en el riesgo de muerte (HR = 1,32; IC95%: 1,24-1,42). Además, los hombres de edad avanzada, de raza negra o indígena, con múltiples comorbilidades y sometidos a ventilación invasiva tienen un mayor riesgo de muerte tras la hospitalización. Es necesario que las medidas políticas intersectoriales se dirijan a mitigar los efectos de la pandemia de COVID-19 agravada por la vulnerabilidad social.

Extrapolation of survival curves in health: a methodological approach for direct fitting to aggregated data / Extrapolação de dados curvas de sobrevida em saúde: uma abordagem metodológica ajuste direto com dados agregados

Introduction: Economic evaluation models often adopt long time horizons, making it necessary to extrapolate data from clinical research for economic evaluation models. The common methodological proposals available are strongly based on individual patient data (IPD), a scenario not always feasible for the daily routine of the Health Technology Assessment (HTA). Thus, the objective of this study was to propose a method for extrapolation with survival curves with direct fitting to aggregated data. Methods: The case study consisted of the application of parametric models of survival analysis with the main recommended distributions: exponential, Weibull, log-normal, log-logistics, generalized gamma and Gompertz. The models were adjusted to data from a randomized clinical trial testing therapies (anastrozole and fulvestrant) in the context of metastatic breast cancer with 10 years of follow-up on progression-free survival (PFS) and overall survival (OS). After making the adjustments to the individualized data, obtained by contacting the authors, we sought to validate the application of the adjustment to the aggregated data using nonlinear regressions and optimization algorithms. Both methods were compared in terms of visual inspection and quality of fit (Akaike Information Criteria ­ AIC and Bayesian Information Criteria ­ BIC). Results: In the two treatment arms, the Weibull and generalized gamma distributions were the ones that best fitted the OS data, both in the individualized and in the aggregated approach, according to statistical and visual inspection criteria. For PFS, log-logistic and log-normal curves were used for anastrozole. In the case of fulvestrant, the best choices would be the log-normal and generalized gamma curves for the individualized data and Gompertz and generalized gamma curves for the aggregated data. In terms of visual inspection, the difference was barely perceptible between the use of the individualized and aggregated models. Conclusion: Direct fitting data with survival curves to aggregated data is feasible. Despite differences in the choice of some curves, visual inspection suggests that it is unlikely that these differences have an impact on decision making. The algorithm presented here may be useful in situations where access to IPD is not possible.

Introdução: Os modelos de avaliação econômica frequentemente adotam longos horizontes temporais. Contudo, a pesquisa clínica geralmente tem um curto tempo de seguimento dos participantes, tornando-se necessária a extrapolação de dados para alimentar os modelos de avaliação econômica. As propostas metodológicas disponíveis trabalham fortemente com os dados em sua forma individualizada, cenário nem sempre factível ao cotidiano da Avaliação de Tecnologias em Saúde (ATS). Assim, o objetivo deste estudo foi replicar um método para extrapolação com curvas de sobrevida aplicável a dados agregados. Métodos: O estudo de caso consistiu nas aplicações de modelos paramétricos de análise de sobrevivência com as principais distribuições recomendadas: Exponencial, Weibull, Log-normal, Log-logística, Gama generalizada e Gompertz. Os modelos foram ajustados aos dados de um ensaio clínico randomizado de duas terapias (anastrozol e fulvestranto) no contexto do câncer de mama metastático com 10 anos de seguimento nos desfechos de sobrevida livre de progressão (SLP) e sobrevida global (SG). Após a condução dos ajustes aos dados individualizados, obtidos mediante contato com os autores, buscou-se validar a aplicação do ajuste aos dados agregados com uso de regressões não lineares e algoritmos de otimização. Ambos os métodos foram comparados em termos de inspeção visual e qualidade do ajuste (Akaike Information Criteria ­ AIC). Resultados: Na verificação da aplicação no estudo de caso nos dados dos dois braços de tratamentos, as distribuições Weibull e gama generalizada foram as que melhor se ajustaram aos dados de SG, seja na abordagem individualizada quanto na agregada, segundo critérios estatísticos e de inspeção visual. Para a SLP foram as curvas log-logística e log-normal para o anastrozol. No caso do tratamento com fulvestranto, as melhores escolhas seriam as curvas log-normal e gama generalizada para os dados individualizados e Gompertz e gama generalizada nos dados agregados. Em termos de inspeção visual, a diferença foi pouco perceptível entre o uso do modelo individualizado e agregado. Conclusão: O ajuste de dados com curvas de sobrevida a dados agregados se mostra factível. Apesar de diferenças na escolha algumas curvas, a inspeção visual sugere que é pouco provável que estas diferenças tenham impacto para a tomada de decisão. O algoritmo aqui apresentado pode ser útil nas situações de impossibilidade de acesso aos dados individualizados.

How long does it take to translate research findings into routine healthcare practice?-the case of biological drugs for rheumatoid arthritis in Brazil.

Background: The literature reports long time lags between the several processes involved in the translation of drug research and development into clinical application. To expedite these processes, translational research has emerged as a process that can be applied to reduce the lag between scientific discoveries and their practical application. Thus, the objective of this study was to estimate the time lag in translational research of biological drugs for the treatment of rheumatoid arthritis included in the Brazilian Unified Health System [Sistema Único de Saúde (SUS)]. Methods: A descriptive retrospective study was conducted based on secondary data loaded by SUS users in public sources and systems to estimate the time lag between the publication of phase I clinical trial results to drug use in clinical settings. The dates of translational research activities were identified from markers and steps. Structured searches were conducted in the literature and reports from the National Commission for the Incorporation of Technologies in the SUS (Conitec) as well as from health authorities, and analyzed. Results: Between 2012 and 2019, SUS included five biological agents for the treatment of rheumatoid arthritis. The mean time lag from clinical development to use of these agents was 11.13 years (range, 8.57 to 12.90 years). The mean time lag for the stages of translational research were 5.30 (T1-basic research to clinical research), 5.08 (T2-clinical research to research synthesis), and 0.75 (T3-research synthesis to evidence-based practice) years. A shorter time lag was observed in the Brazilian case when it was possible to compare with other studies. Conclusions: The estimated time lag of biological drugs used in the treatment of rheumatoid arthritis was determined based on the translational research steps model adapted to the Brazilian context. Brazil has instituted legal frameworks that set deadlines for sanitary registration, health technology assessment (HTA), and the availability of drugs in the SUS, thus, allowing for a reduced stage T2 time lag. Nevertheless, improvements are still required in stages T1 and T2, especially in publishing the results of clinical trials.

COVID-19 as the leading cause of hospital deaths in the Brazilian public health system in 2020.

OBJECTIVES: To describe the profile of hospital deaths in Brazil according to cause of admission during the pre-pandemic (2019) and pandemic periods (2020). METHODS: Descriptive study based on individual-level records of all hospital admissions with death outcomes reimbursed by the Brazilian National Health System in 2019 and 2020. RESULTS: The number of hospital deaths increased by 16.7% in 2020 compared with 2019 (522,686 vs 609,755). Coronavirus disease 2019 (COVID-19) was associated with 19.5% (118,879) of all hospital deaths in 2020, surpassing diseases of the circulatory system (15.4%, 93,735) and diseases of the respiratory system (14.9%, 91,035). CONCLUSIONS: COVID-19 was the main cause of death in public hospitals in Brazil in 2020.

Trends in COVID-19 case-fatality rates in Brazilian public hospitals: A longitudinal cohort of 398,063 hospital admissions from 1st March to 3rd October 2020.

BACKGROUND: Almost 200,000 deaths from COVID-19 were reported in Brazil in 2020. The case fatality rate of a new infectious disease can vary by different risk factors and over time. We analysed the trends and associated factors of COVID-19 case fatality rates in Brazilian public hospital admissions during the first wave of the pandemic. METHODS: A retrospective cohort of all COVID-19-related admissions between epidemiological weeks 10-40 in the Brazilian Public Health System (SUS) was delimited from available reimbursement records. Smoothing time series and survival analyses were conducted to evaluate the trends of hospital case fatality rates (CFR) and the probability of death according to factors such as sex, age, ethnicity, comorbidities, length of stay and ICU use. RESULTS: With 398,063 admissions and 86,452 (21.7%) deaths, the overall age-standardized hospital CFR trend decreased throughout the period, varying from 31.8% (95%CI: 31.2 to 32.5%) in week 10 to 18.2% (95%CI: 17.6 to 18.8%) in week 40. This decreasing trend was observed in all sex, age, ethnic groups, length of stay and ICU admissions. Consistently, later admission (from July to September) was an independent protective factor. Patients 80+ year old had a hazard ratio of 8.18 (95% CI: 7.51 to 8.91). Ethnicity, comorbidities, and ICU need were also associated with the death risk. Although also decreasing, the CFR was always around 40-50% in people who needed an ICU admission. CONCLUSIONS: The overall hospital CFR of COVID-19 has decreased in Brazilian public hospitals during the first wave of the pandemic in 2020. Nevertheless, during the entire period, the CFR was still very high, suggesting the need for improving COVID-19 hospital care in Brazil.

Demand for ICU beds by COVID-19 in the Federal District, Brazil: an analysis of the impact of social distance measures with Monte Carlo simulations / Demanda de camas de UCI por COVID-19 en el Distrito Federal, Brasil: un análisis del impacto de las medidas de distancia social con simulaciones de Monte Carlo / Demanda por leitos de UTI pela COVID-19 no Distrito Federal, Brasil: uma análise do impacto das medidas de distanciamento social com simulações de Monte Carlo

Objectives: to analyze the impact of social distance policies on the spread of COVID-19 and the need for beds in intensive care units. Methods: based on a dynamic transition compartmental model and Monte Carlo simulations, propagation scenarios were built according to the level of adherence of the social distance measures in the context of the Federal District, Brazil. The parameter values ​​were based on official sources, indexed databases and public data repositories. Results: maintaining adherence to the 58% isolation level was the only favorable scenario, with a peak of up to 792 (IQR: 447 to 1,262) ICU admissions between 11/05/2020 and 1/15/2021. The absence of social distance would imply a peak of up to 7,331 (IQR: 5,427 to 9,696) ICU admissions. Conclusion: the projections corroborate the positive effect of social distance measures and the applicability of indicators in their monitoring.

Objetivos: analizar el impacto de las políticas de distancia social en la propagación de COVID-19 y la necesidad de camas en unidades de cuidados intensivos. Métodos: con un modelo de transición dinámica y simulaciones de Monte Carlo, los escenarios de propagación se construyeron de acuerdo con el nivel de adherencia de las medidas de distancia social en el Distrito Federal, Brasil. Los parámetros se basaron en fuentes oficiales, bases de datos indexadas y repositorios de datos. Resultados: mantener la adherencia al nivel de aislamiento del 58% fue el único escenario favorable, con un pico de hasta 792 (IQR: 447 a 1,262) admisiones en la UCI entre el 11/05/2020 y el 15/1/2021. La ausencia de distancia implicaría un pico de 7,331 (IQR: 5,427 a 9,696) admisiones en la UCI. Conclusión: las proyecciones corroboran el efecto positivo de las medidas de distancia social y la aplicabilidad de los indicadores en su seguimiento.

Objetivos: analisar o impacto das políticas de distanciamento social sobre a propagação da COVID-19 e a necessidade de leitos de unidades de terapia intensiva. Métodos: com um modelo compartimental de transição dinâmica e simulações de Monte Carlo foram construídos cenários de propagação de acordo com o nível de adesão das medidas de distanciamento social no contexto do Distrito Federal, Brasil. Os valores dos parâmetros foram baseados em fontes oficiais, bases indexadas e repositórios públicos de dados. Resultados: a manutenção da adesão ao nível de 58% de isolamento foi o único cenário favorável, com um pico de até 792 (IQR: 447 a 1.262) internações em UTI entre 05/11/2020 e 15/01/2021. A ausência do distanciamento implicaria um pico de até 7.331 (IQR: 5.427 a 9.696) internações em UTI. Conclusão: as projeções corroboram o efeito positivo das medidas de distanciamento social e a aplicabilidade de indicadores no seu monitoramento.

Long-term real-life outcomes in a georrefered cohort of acromegalic patients in Brazil.

PURPOSE: Epidemiological data on acromegaly therapeutic outcomes in real-life conditions are scarce in Brazil. Information on the geographical accessibility to the dispensation of medicines and its impact on biochemical control is also poorly known. We aimed to describe the clinical outcomes of long-term therapy in patients with acromegaly at a referral medical centre in Brazil and to perform a spatial analysis of patients according to the distance from home to the drug-dispensing pharmacies aiming to evaluate its impact on biochemical control. METHODS: Global retrospective data analysis of 111 patients followed at the University Hospital of Brasília from January 1980 to March 2015 was performed, as well as a separate review of 17 new cases operated on from April 2015 to June 2019 according to surgery results. Spatial analysis of patients under pharmacological treatment applying Geographic Information System (GIS) software (ArcGIS, ESRI, Redlands, CA) was performed. RESULTS: Considering surgery alone, the cure rate was 23% from 1980 to 2015 and 29.4% from 2015 to 2019. In the long-term follow-up of the 111 patients from 1980 to 2015, 25.2% (n = 29) were cured, 40.6% (n = 44) presented controlled disease and 34.2% (n = 38) were biochemically uncontrolled after a period of follow-up of 8.9 ± 6.4 years. Biochemical control obtained in patients on pharmacological treatment (n = 76) was 58% (n = 44) after 5.8 ± 3.8 years. The distance from home to the drug-dispensing pharmacy did not influence biochemical control (p = 0.7616). CONCLUSIONS: Most patients presented with disease under control. No evidence on the effect of the distance between home and drug-dispensing pharmacies on biochemical control was obtained.

Medicamentos e pesquisa translacional: etapas, atores e políticas de saúde no contexto brasileiro / Medicines and translational research: steps, actors, and health policies in the Brazilian context

RESUMO A pesquisa translacional surgiu com o objetivo de reduzir o tempo entre a pesquisa básica e a sua aplicação clínica. Para os medicamentos, esse tempo pode chegar a décadas, o que denota a necessidade de se avaliarem possíveis barreiras por meio da pesquisa translacional. Objetivou-se revisar a literatura para identificar as etapas da pesquisa translacional, bem como os atos normativos, as políticas públicas de saúde e os principais atores no contexto brasileiro. Para a identificação de modelos da pesquisa translacional, realizou-se revisão com busca sistemática nas bases PubMed, Embase e Lilacs, sendo selecionadas 23 publicações. Sítios eletrônicos oficiais foram consultados para o levantamento das políticas e dos atores. Como resultados, a literatura inicialmente apontava uma etapa (da bancada ao leito), incorporando recentemente a síntese de pesquisas e a avaliação de impacto na saúde pública como etapas adicionais. Diversos atores são transversais na pesquisa translacional, como universidades, instituições de pesquisa e agências de fomento. Observa-se que o Brasil instituiu políticas importantes nas áreas de assistência farmacêutica, pesquisa, ciência, tecnologia e inovação em saúde, o que pode potencialmente integrar recursos, atores e esforços visando à aplicação prática de resultados para melhorar as condições de saúde e de vida da população.

ABSTRACT Translational research has come up with the purpose of reducing the time gap between basic research and its clinical application. As for what concerns medicines, this time can reach decades, demanding the evaluation of barriers through translational research. Our aim was to review the literature in order to identify the steps of translational research, as well as normative acts, public health policies, and the key agents in the Brazilian context. For the identification of translational research framework, a systematic search was carried out on PubMed, Embase, and Lilacs databases, with 23 publications selected. Official websites were consulted to gather information on policies and actors. As a result, the literature initially pointed to one step (from bench to bedside), recently incorporating the additional steps of research synthesis and the public health impact assessment. Several actors are transversally involved in translational research, such as universities, research institutions, and funding agencies. It is observed that Brazil has implemented important policies in the fields of pharmaceutical services, research, science, technology, and innovation in health, which may potentially integrate resources, actors, and efforts aimed to the practical application of research results in clinical practice, improving the health and life condition of the population.

Target therapy versus dacarbazine in first-line treatment of advanced non-surgical and metastatic melanoma: budget impact analysis from the perspective of the Brazilian National Health System, 2018-2020. / Terapia-alvo versus dacarbazina no tratamento de primeira linha do melanoma avançado não cirúrgico e metastático: análise de impacto orçamentário na perspectiva do Sistema Único de Saúde, 2018-2020.

OBJECTIVE: to estimate the incremental budget impact of target therapy for first-line treatment of advanced non-surgical and metastatic melanoma compared to dacarbazine treatment. METHODS: budget impact analysis, from the Brazilian National Health System (SUS) perspective; based on demographic data and incidence estimates, the population over a three-year time horizon (2018-2020) was delimited and the direct medical costs were estimated; the reference scenario was treatment with dacarbazine, and the alternative scenarios were target therapy with vemurafenib, dabrafenib, vemurafenib + cobimetinib and dabrafenib + trametinib; uncertainty assessment was conducted through scenario analysis. RESULTS: the incremental budget impact ranged from R$ 451,867,881.00 to R$ 768,860,968.00, representing 0.70 to 1.53% of total SUS annual outpatient drugs expenditure; in best and worst scenario, results ranged from R$ 289,160,835.00 to R$ 1,107,081,926.00. CONCLUSION: the use of target therapy compared to dacarbazine implies an excessive impact on the budget, this bring unfovorable to its possible incorporation.

Economics of Acromegaly Treatment in Brazil: A Budget Impact Analysis of Pituitary Surgery Compared with Long-Term Octreotide LAR.

BACKGROUND: Acromegaly is a rare, chronic and debilitating disease whose treatment places a high burden on health systems. In the reality of the Brazilian public health network, many patients are kept on drug treatment because of barriers to access to surgery. OBJECTIVE: The aim of this study was to estimate the costs and budget impact of routine transsphenoidal endoscopic surgery in relation to those of long-term drug treatment with octreotide long-acting release (LAR) from a cohort of patients followed at the referral medical centre for acromegaly treatment in the Federal District, Brazil. METHODS: Based on micro-costing data collected using mixed methods from a local perspective of the public health system, we performed a budget impact analysis (BIA) on a 3-year time horizon. Uncertainty was handled with deterministic (tornado and scenario) and probabilistic (Monte Carlo simulations) sensitivity analyses. RESULTS: Compared with the continued use of octreotide LAR at a dose of 30 mg every 28 days, the incremental budget impact of conducting two surgeries per month, considering a cure rate of 55%, could bring savings of approximately US$879,362.18 (95% CI 860,176.29-898,548.08) over 3 years. Depending on the key variable values, the savings amplitude ranged from US$431,836.39 to US$1,519,132.04. CONCLUSIONS: Improving access to surgery could result in significant cost reductions in acromegaly treatment. The present study stands out for being the first to estimate the costs of transsphenoidal surgery in the context of the public health system in Brazil.

Terapia-alvo versus dacarbazina no tratamento de primeira linha do melanoma avançado não cirúrgico e metastático: análise de impacto orçamentário na perspectiva do Sistema Único de Saúde, 2018-2020 / Terapia dirigida versus dacarbazina en el tratamiento de primera línea del melanoma avanzado no quirúrgico y metastásico: análisis de impacto presupuestario en la perspectiva del Sistema Nacional de Salud de Brasil, 2018-2020 / Target therapy versus dacarbazine in first-line treatment of advanced non-surgical and metastatic melanoma: budget impact analysis from the perspective of the Brazilian National Health System, 2018-2020

Objetivo: estimar o impacto orçamentário incremental da terapia-alvo para tratamento de primeira linha do melanoma avançado não cirúrgico e metastático, em comparação à dacarbazina. Métodos: análise de impacto orçamentário na perspectiva do Sistema Único de Saúde (SUS) do Brasil; a partir de dados demográficos e estimativas da incidência, foi delimitada a população no horizonte temporal de três anos (2018-2020) e estimados os custos diretos médicos; foi considerado cenário de referência o tratamento com dacarbazina, e como cenários alternativos a terapia-alvo com vemurafenibe, dabrafenibe, vemurafenibe + cobimetinibe e dabrafenibe + trametinibe; a avaliação das incertezas foi conduzida mediante análise por cenários. Resultados: o impacto orçamentário incremental variou de R$ 451.867.881,00 a R$ 768.860.968,00, representando 0,70 a 1,53% dos gastos anuais totais com medicamentos ambulatoriais no SUS; no melhor e no pior cenário, os resultados variaram de R$ 289.160.835,00 a R$ 1.107.081.926,00. Conclusão: a terapia-alvo, comparada à dacarbazina, implica impacto excessivo no orçamento, desfavorecendo eventual incorporação.

Objetivo: estimar el impacto presupuestario incremental de la terapia dirigida para tratamiento de primera línea del melanoma avanzado no quirúrgico y metastásico comparado con la dacarbazina. Métodos: análisis de impacto presupuestario, en la perspectiva del Sistema Único de Salud (SUS) de Brasil; a partir de datos demográficos y estimaciones de incidencia se delimitó la población en un horizonte temporal de tres años (2018-2020) y se estimaron los costos directos médicos. El escenario de referencia fue el tratamiento con dacarbazina y los escenarios alternativos la terapia dirigida con vemurafenib, dabrafenib, vemurafenib + cobimetinib y dabrafenib + trametinib; la evaluación de incertidumbre se llevó a cabo mediante análisis por escenarios. Resultados: el impacto presupuestario incremental varió de R$ 451.867.881,00 a R$ 768.860.968,00, representando 0,70 a 1,53% de gastos anuales totales con medicamentos de ambulatorios en el SUS; en el mejor y el peor escenario los resultados variaron de R$ 289.160.835,00 a R$ 1.107.081.926,00. Conclusión: el uso de terapia dirigida comparado a la dacarbazina implica en impacto excesivo en el presupuesto, desfavoreciendo una eventual incorporación.

Objective: to estimate the incremental budget impact of target therapy for first-line treatment of advanced non-surgical and metastatic melanoma compared to dacarbazine treatment. Methods: budget impact analysis, from the Brazilian National Health System (SUS) perspective; based on demographic data and incidence estimates, the population over a three-year time horizon (2018-2020) was delimited and the direct medical costs were estimated; the reference scenario was treatment with dacarbazine, and the alternative scenarios were target therapy with vemurafenib, dabrafenib, vemurafenib + cobimetinib and dabrafenib + trametinib; uncertainty assessment was conducted through scenario analysis. Results: the incremental budget impact ranged from R$ 451,867,881.00 to R$ 768,860,968.00, representing 0.70 to 1.53% of total SUS annual outpatient drugs expenditure; in best and worst scenario, results ranged from R$ 289,160,835.00 to R$ 1,107,081,926.00. Conclusion: the use of target therapy compared to dacarbazine implies an excessive impact on the budget, this bring unfovorable to its possible incorporation.

The Assessment for Disinvestment of Intramuscular Interferon Beta for Relapsing-Remitting Multiple Sclerosis in Brazil.

In Brazil, inclusion and exclusion of health technologies within the Unified Health System (SUS) is the responsibility of the National Committee for Health Technology Incorporation (CONITEC). A recent Cochrane systematic review demonstrated that intramuscular interferon beta 1a (IFN-ß-1a-IM) was inferior to the other beta interferons (IFN-ßs) for multiple sclerosis (MS). As a result, CONITEC commissioned an analysis to review possible disinvestment within SUS. The objective of this paper is to describe the disinvestment process for IFN-ß-1a-IM in Brazil. The first assessment comprised a literature review and mixed treatment comparison meta-analysis. The outcome of interest was the proportion of relapse-free patients in 2 years. This analysis confirmed the inferiority of IFN-ß-1a-IM. Following this, CONITEC recommended disinvestment, with the decision sent for public consultation. More than 3000 contributions were made on CONITEC's webpage, most of them against the preliminary decision. As a result, CONITEC commissioned a study to assess the effectiveness of IFN-ß-1a-IM among Brazilian patients in routine clinical care. The second assessment involved an 11-year follow-up of a non-concurrent cohort of 12,154 MS patients developed by deterministic-probabilistic linkage of SUS administrative databases. The real-world assessment further demonstrated that IFN-ß-1a-IM users had a statistically higher risk of treatment failure, defined as treatment switching or relapse treatment or death, with the assessment showing that IFN-ß-1a-IM was inferior to the other IFN-ßs and to glatiramer acetate in both direct and indirect analysis. In the drug ranking with 40,000 simulations, IFN-ß-1a-IM was the worst option, with a success rate of only 152/40,000. Following this, CONITEC decided to exclude the intramuscular presentation of IFN-ß from the current MS treatment guidelines, giving patients who are currently on this treatment the option of continuing until treatment failure. In conclusion, we believe this is the first example of this new disinvestment process in action, providing an exemplar for other treatments in Brazil as well as other countries.