Psychoactive substance consumption after the Fundão dam mine tailing disaster in Minas Gerais State, Brazil.

Disasters cause changes in morbidity, mortality, and medicine use. Brazil is one of the main producers of mineral ores at great environmental cost. Mine tailings are stored in dams and ruptures have led to major disasters. We investigated the consumption of psychoactive medicines in the municipalities affected by the Fundão dam disaster in Minas Gerais State. An ecological study was carried out on drug consumption, estimated using public purchases in Minas Gerais and dispensing data from private retail pharmacies. Consumption (in number of defined daily doses/100,000 inhabitants per day) was analyzed descriptively in eight municipalities, stratified according to consumption level during a 25-month period. Six comparisons of mean consumption values for both data sets were done for pre- and post-disaster periods. The means of medicine consumption before and after the event were plotted and linear trends were added. Public purchase data evinced high consumption levels. Only pharmaceutical retail showed significant differences between the strata in the pre-disaster versus two post-disaster periods. Smaller municipalities showed an increase in consumption 15 months after the disaster. Clonazepam led the way in pharmaceutical retail consumption, followed by fluoxetine. Medicines showed an upward trend after the disaster. The high public provision may have stifled significant consumption patterns of psychoactive drugs; however, peak consumption were observed in private retail, suggesting a modification in use patterns after the disaster. The decrease in consumption immediately after the event was probably related to lower care-seeking behavior on the part of the population, and significant peaks after the disaster may reflect economic consequences of it.

Racial disparities in breast cancer survival after treatment initiation in Brazil: a nationwide cohort study.

BACKGROUND: Breast cancer is a public health priority in Brazil and ensuring equity in health care is one of the cancer control plan goals. Our aim was to present the first assessment on the influence of race or skin colour on breast cancer survival at the national level. METHODS: In this nationwide cohort study, data on women who initiated treatment for breast cancer in the public health-care system (Sistema Unico de Saúde), Brazil, were assembled through record linkage of administrative and mortality information systems. The administrative information systems were the Outpatient Information System (data from high complexity procedure authorisations) and the Hospital Information System (data from hospitalisation authorisations). We included women aged 19 years or older who started treatment between Jan 1, 2008, and Nov 30, 2010; self-identified as having White, Black, or Brown race or skin colour; had tumour stage I-IV; and were treated with chemotherapy or radiotherapy, or both. Patients were followed up until Dec 31, 2015. Patients with only hormone therapy records or who underwent only surgery were excluded. The Kaplan-Meier method was used to estimate crude overall survival for race or skin colour by time since treatment initiation, and Cox regression to estimate all-cause mortality hazard ratios (HRs) before and after adjustment for other covariates. FINDINGS: We identified 59 811 women treated for stage I-IV breast cancer. 37 318 (62·4%) women identified themselves as White, 18 779 (31·4%) as Brown, and 3714 (6·2%) as Black. 5-year overall survival probability was higher for White women (74% [95% CI 73-74]) than Black women (64% [62-65]; p<0·0001). In adjusted regression models stratified by the absence of hormone therapy, Black women had a 24% (HR 1·24 [95% CI 1·16-1·34]; p<0·0001) higher risk of all-cause death than White women, and in the presence of hormone therapy Black women had a 25% (1·25 [1·14-1·38]; p<0·0001) higher risk of all-cause death than White women. INTERPRETATION: Black skin colour was identified as a statistically significant risk marker for lower 5-year survival probability and higher risk of all-cause death among women treated for breast cancer by the Sistema Unico de Saúde. Actions to understand and mitigate this unfair difference in health results are urgently needed. FUNDING: Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior and Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais.

Psychoactive substance consumption after the Fundão dam mine tailing disaster in Minas Gerais State, Brazil / Consumo de psicoativos após o desastre da Barragem de Fundão, em Minas Gerais, Brasil / Consumo de psicoactivos tras el desastre de la presa Fundão, en Minas Gerais, Brasil

Abstract: Disasters cause changes in morbidity, mortality, and medicine use. Brazil is one of the main producers of mineral ores at great environmental cost. Mine tailings are stored in dams and ruptures have led to major disasters. We investigated the consumption of psychoactive medicines in the municipalities affected by the Fundão dam disaster in Minas Gerais State. An ecological study was carried out on drug consumption, estimated using public purchases in Minas Gerais and dispensing data from private retail pharmacies. Consumption (in number of defined daily doses/100,000 inhabitants per day) was analyzed descriptively in eight municipalities, stratified according to consumption level during a 25-month period. Six comparisons of mean consumption values for both data sets were done for pre- and post-disaster periods. The means of medicine consumption before and after the event were plotted and linear trends were added. Public purchase data evinced high consumption levels. Only pharmaceutical retail showed significant differences between the strata in the pre-disaster versus two post-disaster periods. Smaller municipalities showed an increase in consumption 15 months after the disaster. Clonazepam led the way in pharmaceutical retail consumption, followed by fluoxetine. Medicines showed an upward trend after the disaster. The high public provision may have stifled significant consumption patterns of psychoactive drugs; however, peak consumption were observed in private retail, suggesting a modification in use patterns after the disaster. The decrease in consumption immediately after the event was probably related to lower care-seeking behavior on the part of the population, and significant peaks after the disaster may reflect economic consequences of it.

Resumo: Os desastres provocam alterações na morbidade, mortalidade e no uso de medicamentos. O Brasil é líder na produção de minérios com grande custo ambiental. Os rejeitos de mineração são armazenados em barragens e as rupturas dessas barragens têm causados grandes desastres. Investigamos o consumo de medicamentos psicoativos em municípios atingidos pelo desastre da Barragem de Fundão, em Minas Gerais. Foi realizado um estudo ecológico sobre o consumo de medicamentos, com base em dados de compras públicas e distribuição de farmácias privadas do varejo de Minas Gerais. O consumo (em número de doses diárias definidas/100 mil habitantes por dia) foi analisado descritivamente em oito municípios, estratificados segundo o nível de consumo durante um período de 25 meses. Foram feitas seis comparações de valores médios de consumo para os dois conjuntos de dados dos períodos pré- e pós-desastre. Foram calculadas as médias de consumo de medicamentos antes e depois do evento e adicionadas tendências lineares. Os dados de compras públicas mostraram elevados níveis de consumo. Apenas o varejo farmacêutico apresentou diferenças significativas entre os estratos no período pré-desastre versus dois períodos pós-desastre. Municípios menores apresentaram aumento no consumo a partir do 15º mês após o desastre. Clonazepam liderou o consumo no varejo farmacêutico, seguido pela fluoxetina. Os medicamentos apresentaram tendência de alta após o desastre. A elevada oferta pública pode ter afetado os padrões de consumo significativo de medicamentos psicoativos; no entanto, foram observados aumentos no comércio privado, sugerindo alterações nos padrões de uso após o desastre. A diminuição do consumo imediatamente após o evento estava provavelmente relacionada a um menor comportamento de procura de cuidados por parte da população e os aumentos significativos posteriores podem refletir as consequências econômicas do desastre.

Resumen: Los desastres provocan cambios en la morbilidad, mortalidad y en el uso de medicamentos. Brasil es líder en la producción de minerales con grandes costos ambientales. Los desechos mineros se almacenan en represas y las roturas de dichas represas han causado grandes desastres. Investigamos el consumo de medicamentos psicoactivos en municipios afectados por el desastre de la presa de Fundão, en Minas Gerais. Se realizó un estudio ecológico sobre el consumo de medicamentos, con base en datos de compras públicas y distribución en farmacias privadas minoristas de Minas Gerais. El consumo (en número de dosis diarias definidas/100.000 habitantes por día) se analizó descriptivamente en ocho municipios, estratificados según el nivel de consumo durante un período de 25 meses. Se realizaron seis comparaciones de los valores medios de consumo para los dos conjuntos de datos de los períodos anterior y posterior al desastre. Se calculó el consumo medio de medicamentos antes y después del evento y se añadieron las tendencias lineales. Los datos de compras públicas mostraron altos niveles de consumo. Solo el comercio minorista farmacéutico presentó diferencias significativas entre los estratos en el período anterior al desastre frente a dos períodos posteriores al desastre. Los municipios más pequeños presentaron un aumento en el consumo a partir del 15º mes después del desastre. El clonazepam lideró el consumo en el comercio minorista farmacéutico, seguido de la fluoxetina. Los medicamentos presentaron una tendencia al alza después del desastre. La elevada oferta pública puede haber afectado los patrones de consumo significativo de medicamentos psicoactivos; sin embargo, se observaron aumentos en el comercio privado, lo que sugiere cambios en los patrones de uso después del desastre. La disminución del consumo inmediatamente después del evento probablemente relacionada con un menor comportamiento de búsqueda de cuidados por parte de la población, y los aumentos significativos posteriores pueden reflejar las consecuencias económicas del desastre.

Comorbidities and in-hospital death of viral pneumonia adults admitted to SUS (2002-2015).

OBJECTIVE: To identify demographic and clinical characteristics of adult patients hospitalized in the Brazilian Unified Health System (SUS) due to viral pneumonia and investigate the association between some comorbidities and death during hospitalization. METHODS: This retrospective cohort study was conducted with secondary data of adults admitted to SUS due to viral pneumonia between 2002 and 2015. Patient profile was characterized based on demographic and clinical variables. The association between the ten Elixhauser comorbidities and in-hospital death was investigated using Poisson regression models with robust standard errors. Results were quantified as incidence rate ratio (IRR) with 95% confidence intervals (CI), and we built five models using successive inclusion of variables blocks. RESULTS: Hospital admissions for viral pneumonias decreased throughout the study period, and it was observed that 5.8% of hospitalized patients had an in-hospital death. We observed significant differences in demographic and clinical characteristics by comparing individuals who died during hospitalization with those who did not, with the occurrence of one or more comorbidities being more expressive among patients who died. Although not considered risk factors for in-hospital death, chronic pulmonary disease and congestive heart failure were the most common comorbidities. Conversely, IRR for in-hospital death increased with other neurological disorders, diabetes, cancer, obesity, and especially with HIV/AIDS. CONCLUSIONS: Individuals presenting with pulmonary and cardiovascular diseases require proper attention during hospitalization, as well as those with other neurological diseases, diabetes, cancer, obesity, and especially HIV/AIDS. Understanding the influence of chronic diseases on viral infections may support the healthcare system in achieving better outcomes.

[Assessment of Brazilian clinical guidelines in oncology: gaps in drafting, applicability, and editorial independence]. / Avaliação de diretrizes clínicas brasileiras em oncologia: carências no rigor do desenvolvimento, aplicabilidade e independência editorial.

The expansion in the variety of clinical guidelines in oncology is perceptible worldwide, highlighting the need to guarantee the quality of these documents. The study thus aimed to assess the quality of Brazilian national guidelines for treatments of breast, prostate, and colon and rectal cancers. We selected 12 Brazilian guidelines published by four different drafting groups (Ministry of Health, Supplementary Health System, and medical societies and associations), and the AGREE II instrument was applied. In all these guidelines, we identified important weaknesses in more than one Domain, especially low values for "applicability" and "editorial independence". The patterns observed per Domains are more related to the drafting group than the respective clinical conditions. Lower scores in "drafting rigor" and "editorial independence" were obtained by nongovernmental drafting groups, including absence of information or lack of its transparency. Although the "clarity of presentation" in the Ministry of Health guidelines was relatively lower, all the guidelines presented major limitations in "applicability". Consequently, in the overall assessment, none of the guidelines was recommended without modifications, and four were not recommended at all. Finally, it is necessary to upgrade the guidelines according to the underlying evidence ("methodological rigor") and to present the recommended practices in a comprehensible and applicable way ("applicability"), and to mitigate conflicting interests in order to offer cancer patients the best available care in Brazil.

A ampliação da variedade de diretrizes clínicas em oncologia é perceptível em todo o mundo, o que salienta a necessidade de garantir a qualidade destes documentos. Assim, o objetivo do estudo foi avaliar a qualidade de diretrizes nacionais de tratamentos dos cânceres de mama, próstata e de cólon e reto. Foram selecionadas 12 diretrizes brasileiras publicadas por quatro grupos elaboradores distintos (Ministério da Saúde, sistema suplementar de saúde e de sociedades e associações médicas), e aplicado o instrumento AGREE II. Em todas as diretrizes avaliadas foram identificadas fragilidades importantes em mais de um Domínio, com destaque para os baixos valores para "aplicabilidade" e "independência editorial". Os padrões observados por Domínios apresentam-se mais relacionados com o grupo elaborador do que com as condições clínicas tratadas. Menores escores no "rigor do desenvolvimento" e "independência editorial" foram obtidos por grupos elaboradores não governamentais, inclusive com ausência ou falta de transparência nas informações. Mesmo que a "clareza da apresentação" das diretrizes do Ministério da Saúde tenha sido relativamente inferior, na "aplicabilidade" todas apresentaram limitações expressivas. Consequentemente, na avaliação global nenhuma das diretrizes foi recomendada sem modificações, sendo quatro delas não recomendadas. Por fim, é necessário qualificar as recomendações no que tange as evidências que as fundamentam ("rigor metodológico"), assim como dispor de forma compreensível e exequível as condutas a serem adotadas ("aplicabilidade") e mitigar interesses conflitantes, para que seja ofertado o melhor cuidado aos pacientes oncológicos no país.

La ampliación de la variedad de directrices clínicas en oncología es perceptible en todo el mundo, lo que resalta la necesidad de garantizar la calidad de estos documentos. Por este motivo, el objetivo de este estudio fue evaluar la calidad de directrices nacionales de tratamientos de los cánceres de mama, próstata, así como de colon y recto. Se seleccionaron doce directrices brasileñas, publicadas por cuatro grupos elaboradores distintos (Ministerio de Salud, sistema suplementario de salud, así como sociedades y asociaciones médicas), y se aplicó el instrumento AGREE II. En todas las directrices evaluadas se identificaron debilidades importantes en más de un Dominio, destacando los bajos valores para la "aplicabilidad" e "independencia editorial". Los patrones observados por Dominios se presentan más relacionados con el grupo elaborador, que con las condiciones clínicas tratadas. Menores puntuaciones en el "rigor del desarrollo" e "independencia editorial" se obtuvieron por parte de grupos elaboradores no gubernamentales, inclusive con ausencia o falta de transparencia en la información. A pesar de que la "claridad de la presentación" de las directrices del Ministerio de la Salud haya sido relativamente inferior en la "aplicabilidad", todas presentaron limitaciones expresivas. Consecuentemente, en la evaluación global, ninguna de las directrices fue recomendada sin modificaciones, siendo cuatro de ellas no recomendadas. Por fin, se hace necesario cualificar las recomendaciones, en lo que se refiere a las evidencias que las fundamentan ("rigor metodológico"), así como disponer de forma comprensible y factible las conductas que deben ser adoptadas ("aplicabilidad"), al igual que mitigar intereses conflictivos, para que sea ofertado el mejor cuidado a los pacientes oncológicos en el país.

Comorbidities and in-hospital death of viral pneumonia adults admitted to SUS (2002-2015)

ABSTRACT OBJECTIVE To identify demographic and clinical characteristics of adult patients hospitalized in the Brazilian Unified Health System (SUS) due to viral pneumonia and investigate the association between some comorbidities and death during hospitalization. METHODS This retrospective cohort study was conducted with secondary data of adults admitted to SUS due to viral pneumonia between 2002 and 2015. Patient profile was characterized based on demographic and clinical variables. The association between the ten Elixhauser comorbidities and in-hospital death was investigated using Poisson regression models with robust standard errors. Results were quantified as incidence rate ratio (IRR) with 95% confidence intervals (CI), and we built five models using successive inclusion of variables blocks. RESULTS Hospital admissions for viral pneumonias decreased throughout the study period, and it was observed that 5.8% of hospitalized patients had an in-hospital death. We observed significant differences in demographic and clinical characteristics by comparing individuals who died during hospitalization with those who did not, with the occurrence of one or more comorbidities being more expressive among patients who died. Although not considered risk factors for in-hospital death, chronic pulmonary disease and congestive heart failure were the most common comorbidities. Conversely, IRR for in-hospital death increased with other neurological disorders, diabetes, cancer, obesity, and especially with HIV/AIDS. CONCLUSIONS Individuals presenting with pulmonary and cardiovascular diseases require proper attention during hospitalization, as well as those with other neurological diseases, diabetes, cancer, obesity, and especially HIV/AIDS. Understanding the influence of chronic diseases on viral infections may support the healthcare system in achieving better outcomes.

Avaliação de diretrizes clínicas brasileiras em oncologia: carências no rigor do desenvolvimento, aplicabilidade e independência editorial / Assessment of Brazilian clinical guidelines in oncology: gaps in drafting, applicability, and editorial independence / Evaluación de directrices clínicas brasileñas en oncología: carencias en el rigor del desarrollo, aplicabilidad e independencia editorial

A ampliação da variedade de diretrizes clínicas em oncologia é perceptível em todo o mundo, o que salienta a necessidade de garantir a qualidade destes documentos. Assim, o objetivo do estudo foi avaliar a qualidade de diretrizes nacionais de tratamentos dos cânceres de mama, próstata e de cólon e reto. Foram selecionadas 12 diretrizes brasileiras publicadas por quatro grupos elaboradores distintos (Ministério da Saúde, sistema suplementar de saúde e de sociedades e associações médicas), e aplicado o instrumento AGREE II. Em todas as diretrizes avaliadas foram identificadas fragilidades importantes em mais de um Domínio, com destaque para os baixos valores para "aplicabilidade" e "independência editorial". Os padrões observados por Domínios apresentam-se mais relacionados com o grupo elaborador do que com as condições clínicas tratadas. Menores escores no "rigor do desenvolvimento" e "independência editorial" foram obtidos por grupos elaboradores não governamentais, inclusive com ausência ou falta de transparência nas informações. Mesmo que a "clareza da apresentação" das diretrizes do Ministério da Saúde tenha sido relativamente inferior, na "aplicabilidade" todas apresentaram limitações expressivas. Consequentemente, na avaliação global nenhuma das diretrizes foi recomendada sem modificações, sendo quatro delas não recomendadas. Por fim, é necessário qualificar as recomendações no que tange as evidências que as fundamentam ("rigor metodológico"), assim como dispor de forma compreensível e exequível as condutas a serem adotadas ("aplicabilidade") e mitigar interesses conflitantes, para que seja ofertado o melhor cuidado aos pacientes oncológicos no país.

The expansion in the variety of clinical guidelines in oncology is perceptible worldwide, highlighting the need to guarantee the quality of these documents. The study thus aimed to assess the quality of Brazilian national guidelines for treatments of breast, prostate, and colon and rectal cancers. We selected 12 Brazilian guidelines published by four different drafting groups (Ministry of Health, Supplementary Health System, and medical societies and associations), and the AGREE II instrument was applied. In all these guidelines, we identified important weaknesses in more than one Domain, especially low values for "applicability" and "editorial independence". The patterns observed per Domains are more related to the drafting group than the respective clinical conditions. Lower scores in "drafting rigor" and "editorial independence" were obtained by nongovernmental drafting groups, including absence of information or lack of its transparency. Although the "clarity of presentation" in the Ministry of Health guidelines was relatively lower, all the guidelines presented major limitations in "applicability". Consequently, in the overall assessment, none of the guidelines was recommended without modifications, and four were not recommended at all. Finally, it is necessary to upgrade the guidelines according to the underlying evidence ("methodological rigor") and to present the recommended practices in a comprehensible and applicable way ("applicability"), and to mitigate conflicting interests in order to offer cancer patients the best available care in Brazil.

La ampliación de la variedad de directrices clínicas en oncología es perceptible en todo el mundo, lo que resalta la necesidad de garantizar la calidad de estos documentos. Por este motivo, el objetivo de este estudio fue evaluar la calidad de directrices nacionales de tratamientos de los cánceres de mama, próstata, así como de colon y recto. Se seleccionaron doce directrices brasileñas, publicadas por cuatro grupos elaboradores distintos (Ministerio de Salud, sistema suplementario de salud, así como sociedades y asociaciones médicas), y se aplicó el instrumento AGREE II. En todas las directrices evaluadas se identificaron debilidades importantes en más de un Dominio, destacando los bajos valores para la "aplicabilidad" e "independencia editorial". Los patrones observados por Dominios se presentan más relacionados con el grupo elaborador, que con las condiciones clínicas tratadas. Menores puntuaciones en el "rigor del desarrollo" e "independencia editorial" se obtuvieron por parte de grupos elaboradores no gubernamentales, inclusive con ausencia o falta de transparencia en la información. A pesar de que la "claridad de la presentación" de las directrices del Ministerio de la Salud haya sido relativamente inferior en la "aplicabilidad", todas presentaron limitaciones expresivas. Consecuentemente, en la evaluación global, ninguna de las directrices fue recomendada sin modificaciones, siendo cuatro de ellas no recomendadas. Por fin, se hace necesario cualificar las recomendaciones, en lo que se refiere a las evidencias que las fundamentan ("rigor metodológico"), así como disponer de forma comprensible y factible las conductas que deben ser adoptadas ("aplicabilidad"), al igual que mitigar intereses conflictivos, para que sea ofertado el mejor cuidado a los pacientes oncológicos en el país.

[Budget impact of the incorporation of second-line drug treatment for diabetic macular edema in the Brazilian Unified National Health System from the perspective of the Minas Gerais State Health Department, Brazil]. / Impacto orçamentário da incorporação de medicamentos para tratamento em segunda linha do edema macular diabético no SUS sob a perspectiva da Secretaria de Estado de Saúde de Minas Gerais, Brasil.

The study's objective was to perform budget impact assessment for the incorporation of second-line intravitreal antiangiogenic therapy for diabatic macular edema in the scope of the Brazilian Unified National Health System (SUS) in Minas Gerais state, Brazil, discussing the incorporation's state budget feasibility. The budget impact assessment was performed as a deterministic method according to Ministry of Health guidelines. The study included patients with probable first-line treatment failure in a five-year timeline for all the technologies assessed. The analysis included the drugs bevacizumab (off-label use), ranibizumab, and aflibercept. The populations were calculated both by observed demand and epidemiological estimate. The following sensitivity analyses were performed: a scenario with slower technology diffusion, a scenario with the market entry of biosimilar versions of bevacizumab and ranibizumab, and a scenario disregarding inflation during the period. The incremental budget impacts according to observed and epidemiologically estimated demand, respectively, were BRL 69,493,906.95 to BRL 473,226,278.78 for bevacizumab; BRL 349,319,965.60 to BRL 2,378,732,103.09 for ranibizumab; and BRL 543,867,485.47 to BRL 3,703,524,490.16 for aflibercept. Bevacizumab proved to be the most financially feasible alternative in all the scenarios of estimates and sensitivity analyses. An increment of nearly 3% was estimated, compared to the 2016 budget (observed demand). The study showed that the incorporation is feasible in the SUS, Minas Gerais State, but subject to management priorities. Price discrepancies between products with similar efficacy is intriguing and provides fertile ground for future studies.

Os objetivos foram efetuar a análise do impacto orçamentário para a incorporação de segunda linha terapêutica com terapia antiangiogênica de aplicação intravítrea, para tratamento de edema macular diabético, no âmbito do Sistema Único de Saúde (SUS) em Minas Gerais, Brasil, discutindo sua viabilidade à luz do orçamento do estado. A análise do impacto orçamentário com método determinístico, segundo diretriz do Ministério da Saúde. Foram incluídos os pacientes com provável falha ao tratamento de primeira linha, num horizonte temporal de 5 anos para todas as tecnologias avaliadas. Incluíram-se na análise os medicamentos bevacizumabe (uso off-label), ranibizumabe e aflibercepte. As populações foram calculadas tanto por demanda aferida quanto por estimativa epidemiológica. Como análises de sensibilidade efetuaram-se: cenário com difusão de tecnologia mais lenta; cenário com a entrada de bevacizumabe e ranibizumabe biossimilares no mercado; cenário com a desconsideração da inflação no período. O impacto orçamentário incremental, de acordo com as estimativas de demanda aferida e epidemiológica, respectivamente, foi de R$ 69.493.906,95-R$ 473.226.278,78 para bevacizumabe; R$ 349.319.965,60-R$ 2.378.732.103,09 para ranibizumabe e R$543.867.485,47-R$ 3.703.524.490,16 para aflibercepte. Bevacizumabe foi a alternativa financeiramente mais viável em todos os cenários das estimativas e análises de sensibilidade. Estimou-se incremento próximo a 3%, comparando com o orçamento de 2016 (demanda aferida). Avalia-se que a incorporação é viável dentro do SUS em Minas Gerais, mas sujeita às prioridades da gestão. A discrepância de preços entre produtos de eficácia semelhante é intrigante e tema fértil para estudos futuros.

El objetivo fue efectuar un análisis del impacto presupuestario en la incorporación de una segunda línea terapéutica, con terapia antiangiogénica de aplicación intravítrea, para el tratamiento de edema macular diabético, en el ámbito del Sistema Único de Salud (SUS), en Minas Gerais, Brasil, discutiendo su viabilidad respecto al presupuesto del estado. Se realizó una análisis del impacto presupuestario con un método determinístico, según la directriz del Ministerio de Salud. Se incluyeron pacientes con probable fracaso al tratamiento de primera línea, en un horizonte temporal de 5 años para todas las tecnologías evaluadas. Se incluyeron en el análisis los medicamentos bevacizumab (uso off-label), ranibizumab y aflibercept. Las poblaciones se calcularon tanto por demanda evaluada, como por estimación epidemiológica. A modo de análisis de sensibilidad se planteó un escenario con una difusión de tecnología más lenta, un escenario con la entrada de bevacizumab y ranibizumab biosimilares en el mercado, y un escenario con la desconsideración de la inflación durante el período. El incremento del impacto presupuestario, de acuerdo con las estimativas de demanda evaluada y epidemiológica, respectivamente, fue BRL 69.493.906,95-BRL 473.226.278,78 en el caso del bevacizumab; BRL 349.319.965,60-BRL 2.378.732.103,09 en el de ranibizumab y BRL 543.867.485,47-BRL 3.703.524.490,16 en el aflibercept. El bevacizumab se mostró la alternativa financiera más viable en todos los escenarios de estimaciones y análisis de sensibilidad. Se estimó un incremento cercano al 3%, comparándolo con el presupuesto de 2016 (demanda evaluada). Se considera que la incorporación es viable dentro del SUS en Minas Gerais, pero sujeta a las prioridades de la gestión. La discrepancia de precios entre productos de eficacia semejante es intrigante y un tema fértil para estudios futuros.

Impacto orçamentário da incorporação de medicamentos para tratamento em segunda linha do edema macular diabético no SUS sob a perspectiva da Secretaria de Estado de Saúde de Minas Gerais, Brasil / Budget impact of the incorporation of second-line drug treatment for diabetic macular edema in the Brazilian Unified National Health System from the perspective of the Minas Gerais State Health Department, Brazil / Impacto presupuestario de la incorporación de medicamentos para un tratamiento de segunda línea del edema macular diabético en el Sistema Único de Salud, desde la perspectiva de la Secretaría Estatal de Salud de Minas Gerais, Brasil

Resumo: Os objetivos foram efetuar a análise do impacto orçamentário para a incorporação de segunda linha terapêutica com terapia antiangiogênica de aplicação intravítrea, para tratamento de edema macular diabético, no âmbito do Sistema Único de Saúde (SUS) em Minas Gerais, Brasil, discutindo sua viabilidade à luz do orçamento do estado. A análise do impacto orçamentário com método determinístico, segundo diretriz do Ministério da Saúde. Foram incluídos os pacientes com provável falha ao tratamento de primeira linha, num horizonte temporal de 5 anos para todas as tecnologias avaliadas. Incluíram-se na análise os medicamentos bevacizumabe (uso off-label), ranibizumabe e aflibercepte. As populações foram calculadas tanto por demanda aferida quanto por estimativa epidemiológica. Como análises de sensibilidade efetuaram-se: cenário com difusão de tecnologia mais lenta; cenário com a entrada de bevacizumabe e ranibizumabe biossimilares no mercado; cenário com a desconsideração da inflação no período. O impacto orçamentário incremental, de acordo com as estimativas de demanda aferida e epidemiológica, respectivamente, foi de R$ 69.493.906,95-R$ 473.226.278,78 para bevacizumabe; R$ 349.319.965,60-R$ 2.378.732.103,09 para ranibizumabe e R$543.867.485,47-R$ 3.703.524.490,16 para aflibercepte. Bevacizumabe foi a alternativa financeiramente mais viável em todos os cenários das estimativas e análises de sensibilidade. Estimou-se incremento próximo a 3%, comparando com o orçamento de 2016 (demanda aferida). Avalia-se que a incorporação é viável dentro do SUS em Minas Gerais, mas sujeita às prioridades da gestão. A discrepância de preços entre produtos de eficácia semelhante é intrigante e tema fértil para estudos futuros.

Abstract: The study's objective was to perform budget impact assessment for the incorporation of second-line intravitreal antiangiogenic therapy for diabatic macular edema in the scope of the Brazilian Unified National Health System (SUS) in Minas Gerais state, Brazil, discussing the incorporation's state budget feasibility. The budget impact assessment was performed as a deterministic method according to Ministry of Health guidelines. The study included patients with probable first-line treatment failure in a five-year timeline for all the technologies assessed. The analysis included the drugs bevacizumab (off-label use), ranibizumab, and aflibercept. The populations were calculated both by observed demand and epidemiological estimate. The following sensitivity analyses were performed: a scenario with slower technology diffusion, a scenario with the market entry of biosimilar versions of bevacizumab and ranibizumab, and a scenario disregarding inflation during the period. The incremental budget impacts according to observed and epidemiologically estimated demand, respectively, were BRL 69,493,906.95 to BRL 473,226,278.78 for bevacizumab; BRL 349,319,965.60 to BRL 2,378,732,103.09 for ranibizumab; and BRL 543,867,485.47 to BRL 3,703,524,490.16 for aflibercept. Bevacizumab proved to be the most financially feasible alternative in all the scenarios of estimates and sensitivity analyses. An increment of nearly 3% was estimated, compared to the 2016 budget (observed demand). The study showed that the incorporation is feasible in the SUS, Minas Gerais State, but subject to management priorities. Price discrepancies between products with similar efficacy is intriguing and provides fertile ground for future studies.

Resumen: El objetivo fue efectuar un análisis del impacto presupuestario en la incorporación de una segunda línea terapéutica, con terapia antiangiogénica de aplicación intravítrea, para el tratamiento de edema macular diabético, en el ámbito del Sistema Único de Salud (SUS), en Minas Gerais, Brasil, discutiendo su viabilidad respecto al presupuesto del estado. Se realizó una análisis del impacto presupuestario con un método determinístico, según la directriz del Ministerio de Salud. Se incluyeron pacientes con probable fracaso al tratamiento de primera línea, en un horizonte temporal de 5 años para todas las tecnologías evaluadas. Se incluyeron en el análisis los medicamentos bevacizumab (uso off-label), ranibizumab y aflibercept. Las poblaciones se calcularon tanto por demanda evaluada, como por estimación epidemiológica. A modo de análisis de sensibilidad se planteó un escenario con una difusión de tecnología más lenta, un escenario con la entrada de bevacizumab y ranibizumab biosimilares en el mercado, y un escenario con la desconsideración de la inflación durante el período. El incremento del impacto presupuestario, de acuerdo con las estimativas de demanda evaluada y epidemiológica, respectivamente, fue BRL 69.493.906,95-BRL 473.226.278,78 en el caso del bevacizumab; BRL 349.319.965,60-BRL 2.378.732.103,09 en el de ranibizumab y BRL 543.867.485,47-BRL 3.703.524.490,16 en el aflibercept. El bevacizumab se mostró la alternativa financiera más viable en todos los escenarios de estimaciones y análisis de sensibilidad. Se estimó un incremento cercano al 3%, comparándolo con el presupuesto de 2016 (demanda evaluada). Se considera que la incorporación es viable dentro del SUS en Minas Gerais, pero sujeta a las prioridades de la gestión. La discrepancia de precios entre productos de eficacia semejante es intrigante y un tema fértil para estudios futuros.

Discontinuation of non-anti-TNF drugs for rheumatoid arthritis in interventional versus observational studies: a systematic review and meta-analysis.

PURPOSE: Although randomized controlled trials (RCTs) are the gold standard for the assessment of clinical outcomes, long-term extension trials (LTEs) and observational cohorts may help generate evidence. Our goal was to compare the discontinuation rates of abatacept, rituximab, and tocilizumab in rheumatoid arthritis (RA) reported in different study designs. METHODS: A systematic review was conducted with searches in PubMed, Scopus, and the Cochrane Library, plus a manual search, for RCTs, LTEs, and observational cohorts reporting discontinuation rates by any of three causes (all-cause, inefficacy, adverse events). Meta-analyses with sensitivity analyses and meta-regressions were conducted. RESULTS: Of the 111 studies included, 74 were RCTs (n = 55) or LTEs (n = 17) reporting data on abatacept (n = 33), rituximab (n = 10), and tocilizumab (n = 31) and 37 were observational cohort studies (abatacept = 11, rituximab = 8, tocilizumab = 18). The follow-up duration did not differ among the study designs. Discontinuation rates were similar among the drugs but varied among the study designs. Discontinuation rates were significantly higher in cohort studies than those in interventional studies for the three drugs. Sensitivity analyses could not identify patient characteristics associated with these differences. Meta-regression analyses demonstrated no correlation between study follow-up duration and discontinuation rates. CONCLUSIONS: The discontinuation rates reported for non-anti-TNF drugs varied relative to the study design in which they were investigated. Regulatory agencies, price-setting entities, and evidence-gathering researchers should consider the effect of the real-life environment in their decisions and conclusions.

Treatment interruption of biological drugs and tofacitinib in rheumatoid arthritis: A systematic review of case reports

The aim of this study was to evaluate interruption of treatment with biological drugs and tofacitinib due to adverse events in patients with rheumatoid arthritis. A systematic review was performed in the electronic databases MEDLINE, Cochrane, Scopus, CRD, IPA, Lilacs and Scielo. Case reports addressing interruption of treatment due to any adverse event related to abatacept (ABA), adalimumab (ADA), anakinra (ANA), certolizumab pegol (CER), etanercept (ETA), golimumab (GOL), infliximab (IFX), rituximab (RTX), secukinumab (SEC), tocilizumab (TCZ), tofacitinib (TOF) or ustekinumab (UST) in rheumatoid arthritis patients were evaluated. Baseline data, patient profile, previous and current treatments, cause of discontinuation and information on reintroduction of treatment were extracted from the case reports. One hundred and fifty-four studies (154 patients) reported 162 discontinuations of rheumatoid arthritis treatment due to adverse events (ETA = 57; IFX = 46; ADA = 32; TCZ = 13; RTX = 5; ANA = 3; GOL = 2; ABA = 2; TOF = 1; CER = 1; SEC = 0 and UST = 0). The mean age of patients was 56 (± 12.1) years and 82% were female. Seventy-four adverse events were confirmed (related to used drug), and 138 were observed in patients using anti-TNF. The most common adverse events were infections (21%), skin disease (15%), autoimmune disease (13%) and hematological disorders (9%). Case reports are important in the detection of rare adverse events and should be considered in the choice of appropriate therapy for patients.

New drugs for the treatment of agitation in schizophrenia: a systematic review and meta-analysis of inhaled loxapine and infused sodium nitroprusside / Novos fármacos para o tratamento da agitação na esquizofrenia: revisão sistemática e meta-análise da loxapina inalável e nitroprussiato de sódio

The use of novel drugs such as inhaled loxapine (LOXi) for schizophrenia and the off-label use of substances such as sodium nitroprusside (NIT) for the management of mental disorders require further investigation. We aimed to evaluate the efficacy and safety of LOXi and NIT for the treatment of agitation associated with schizophrenia. A systematic review of randomized controlled trials (RCTs) comparing the use of LOXi or NIT versus placebo or other antipsychotic agents was conducted, and we evaluated the efficacy (CGI-scale) and safety (adverse events) of the therapies. Altogether, 71 studies were identified, of which 2 (LOXi) were included in the meta-analysis, and 1 (NIT) was included in the systematic review only. The efficacy data showed superiority of LOXi against placebo, regardless of the dose (5 and 10 mg). No significant differences were observed concerning the safety results. Treatment with NIT showed favorable results, with significant reduction of the symptoms. The efficacy of these medications is difficult to assess because of the lack of RCTs. However, there is some information regarding the efficacy and safety of LOXi in the treatment of agitation in schizophrenic patients.

Fármacos mais recentes como a loxapina inalável (LOXi) para o tratamento da esquizofrenia e o uso off- label de substâncias como o nitroprussiato de sódio (NIT) para o manejo de desordens mentais requerem mais investigações. O objetivo do estudo foi avaliar eficácia e segurança da LOXi e do NIT para tratamento da agitação na esquizofrenia. Foi realizada revisão sistemática de ensaios clínicos randomizados (ECR) comparando o uso de LOXi ou NIT versus placebo ou outros antipsicóticos. Foram avaliados desfechos de eficácia (escala CGI-I) e segurança (eventos adversos). Ao todo 71 estudos foram identificados, dos quais dois foram incluídos nas meta-análises (ambos da LOXi) e 1 sobre NIT foi incluído somente na revisão sistemática. Os dados de eficácia demonstraram superioridade da LOXi frente ao placebo, independente das doses avaliadas (5 ou 10 mg). Não foram observadas diferenças significativas entre os resultados de segurança com o controle. O único estudo incluído sobre o NIT mostrou resultados favoráveis, com redução significativa dos sintomas. Apesar da carência de ECR com esses fármacos dificultar a determinação e a reunião de informações, há potenciais evidências de eficácia e segurança da LOXi no tratamento da agitação em pacientes com esquizofrenia.

Adverse events and treatment failure leading to discontinuation of recently approved antipsychotic drugs in schizophrenia: A network meta-analysis.

Objective:We aimed to gather evidence of the discontinuation rates owing to adverse events or treatment failure for four recently approved antipsychotics (asenapine, blonanserin, iloperidone, and lurasidone).Methods: A systematic review followed by pairwise meta-analysis and mixed treatment comparison meta analysis(MTC) was performed, including randomized controlled trials (RCTs) that compared the use of the above-mentioned drugs versus placebo in patients with schizophrenia. An electronic search was conducted in PubMed, Scopus, Science Direct, Scielo, the Cochrane Library, and International Pharmaceutical Abstracts(January 2015). The included trials were at least single blinded. The main outcome measures extracted were discontinuation owing to adverse events and discontinuation owing to treatment failure.Results: Fifteen RCTs were identified (n = 5400 participants) and 13 of them were amenable for use in our meta-analyses. No significant differences were observed between any of the four drugs and placebo as regards discontinuation owing to adverse events, whether in pairwise meta-analysis or in MTC. All drugs presented a better profile than placebo on discontinuation owing to treatment failure, both in pairwise meta-analysis and MTC. Asenapine was found to be the best therapy in terms of tolerability owing to failure,while lurasidone was the worst treatment in terms of adverse events. The evidence around blonanserin is weak.Conclusion: MTCs allowed the creation of two different rank orders of these four antipsychotic drugs in two outcome measures. This evidence-generating method allows direct and indirect comparisons, supporting approval and pricing decisions when lacking sufficient, direct, head-to-head trials.