RESUMO
Introdução: Pacientes com leucemia linfocítica crônica (LLC) com alto risco têm menores taxas de resposta, curso clínico mais agressivo e resistência à quimioterapia padrão, representando um desafio para o tratamento. Os inibidores da tirosina quinase de Bruton (BTK ibrutinibe e acalabrutinibe) e o inibidor BCL-2 (venetoclax) podem ser utilizados nesses casos. Objetivo: Identificar e avaliar a eficácia e a segurança do uso de ibrutinibe, acalabrutinibe e venetoclax no tratamento de primeira linha em pacientes com LLC de alto risco. Método: Revisão sistemática de ensaios clínicos randomizados que avaliaram pacientes adultos com LLC, portadores de deleção 17p ou mutação TP53 e sem tratamento prévio. Foram pesquisadas as bases PubMed, EMBASE, LILACS e Cochrane Library, e realizadas avaliação do risco de viés pela ferramenta RoB 2 da Cochrane e avaliação da qualidade da evidência pelo GRADE. Resultados: Na meta-análise em rede para sobrevida livre de progressão (SLP), venetoclax + obinutuzumabe (RR: 0,62; IC 95% 0,41-0,95; p = 0,027) e acalabrutinibe + obinutuzumabe (RR: 0,74; IC 95% 0,55-0,99; p = 0,043) apresentaram menor risco de progressão ou óbito, com significância considerada limítrofe. Ibrutinibe + obinutuzumabe (RR: 0,93; IC 95% 0,86-1,00; p = 0,054) não apresentou diferença significativa na SLP para pacientes com LLC de alto risco. Conclusão: O tratamento de primeira linha com inibidores de BTK (ibrutinibe e acalabrutinibe) e o inibidor BCL-2 (venetoclax), associados a agentes monoclonais anti-CD20 especialmente o obinutuzumabe , tem sido proposto como padrão para a maioria dos pacientes com LLC. Entretanto, pelos resultados desta revisão com meta-análise em rede, não foi possível confirmar essa recomendação.
Introduction: Patients with high-risk chronic lymphocytic leukemia (CLL) have lower response rates, a more aggressive clinical course, and resistance to standard chemotherapy, representing a treatment challenge. Bruton's tyrosine kinase inhibitors (BTK ibrutinib and acalabrutinib) and the BCL-2 inhibitor (venetoclax) can be used in these cases. Objective: To identify and evaluate studies on the efficacy and safety of the use of ibrutinib, acalabrutinib and venetoclax in first-line treatment in patients with high-risk CLL. Method:Systematic review of randomized clinical trials that evaluated adult patients with CLL, carriers of 17p deletion or TP53 mutation and without prior treatment. The PubMed, EMBASE, LILACS and Cochrane Library databases were searched, and the risk of bias was assessed using the Cochrane RoB 2 tool and the quality of evidence was assessed with GRADE. Results: In the network meta-analysis for progression-free survival (PFS) venetoclax + obinutuzumab (RR: 0.62; 95%CI 0.41-0.95; p value 0.027) and acalabrutinib + obinutuzumab (RR: 0. 74; 95% CI 0.55-0.99; p value 0.043) presented a lower risk of progression or death, with significance considered borderline. Ibrutinib + obinutuzumab (RR: 0.93; 95% CI 0.86-1.00; p value 0.054) did not show a significant difference in PFS for patients with high-risk CLL. Conclusion: First-line treatment with BTK inhibitors (ibrutinib and acalabrutinib) and the BCL-2 inhibitor (venetoclax) associated with anti-CD20 monoclonal agents especially obinutuzumab have been proposed as the standard for most patients with CLL. However, based on the results of this review with network meta-analysis, it was not possible to confirm this recommendation.
Introducción: Los pacientes con leucemia linfocítica crónica (LLC) de alto riesgo tienen tasas de respuesta más bajas, un curso clínico más agresivo y resistencia a la quimioterapia estándar, lo que representa un desafío para el tratamiento. En estos casos se pueden utilizar los inhibidores de la tirosina quinasa de Bruton (BTK - ibrutinib y acalabrutinib) y el inhibidor de BCL-2 (venetoclax). Objetivo:Identificar y evaluar estudios sobre la eficacia y seguridad del uso de ibrutinib, acalabrutinib y venetoclax en el tratamiento de primera línea en pacientes con LLC de alto riesgo. Método: Revisión sistemática de ensayos clínicos aleatorios que evaluaron pacientes adultos con LLC, portadores de deleción 17p o mutación TP53 y sin tratamiento previo. Se realizaron búsquedas en las bases de datos PubMed, EMBASE, LILACS y Cochrane Library y se evaluó el riesgo de sesgo mediante la herramienta Cochrane RoB 2 y la calidad de la evidencia se evaluó mediante GRADE. Resultados: En el metaanálisis en red para la supervivencia libre de progresión (SSP) venetoclax + obinutuzumab (RR: 0,62; IC 95% 0,41-0,95; valor de p 0,027) y acalabrutinib + obinutuzumab (RR: 0,74; IC 95%). 0,55-0,99; valor de p 0,043) presentaron un menor riesgo de progresión o muerte, con una significación considerada límite. Ibrutinib + obinutuzumab (RR: 0,93; IC del 95 %: 0,86-1,00; valor de p 0,054) no mostró una diferencia significativa en la SSP para pacientes con LLC de alto riesgo. Conclusión: El tratamiento de primera línea con inhibidores de BTK (ibrutinib y acalabrutinib) y el inhibidor de BCL-2 (venetoclax), asociados con agentes monoclonales anti-CD20, especialmente obinutuzumab, se ha propuesto como estándar para la mayoría de los pacientes con LLC. Sin embargo, según los resultados de esta revisión con metaanálisis en red, no fue posible confirmar esta recomendación
Assuntos
Leucemia Linfocítica Crônica de Células B , Inibidores de Tirosina Quinases , Protocolos Antineoplásicos , Metanálise em Rede , Revisão SistemáticaRESUMO
Economic assessments are relevant to support the decision to incorporate more cost-effective strategies to reduce Cervical Cancer (CC) mortality. This systematic review analyzes the economic evaluation studies of CC prevention strategies (HPV DNA-based tests and conventional cytology) in low- and middle-income countries. Medline, EMBASE, CRD, and LILACS were searched for economic evaluation studies that reported cost and effectiveness measures of HPV DNA-based tests for CC screening and conventional cytology in women, without age, language, or publication date restrictions. Selection and data extraction were carried out independently. For comparability of results, cost-effectiveness measures were converted to international dollars (2019). Report quality was assessed using the CHEERS checklist. The Dominance Matrix Ranking (DRM) was used to analyze and interpret the results. The review included 15 studies from 12 countries, with cost-effectiveness analyzes from the health system's perspective and a 3% discount rate. The strategies varied in age and frequency of screening. Most studies used the Markov analytical model, and the cost-benefit threshold was based on the per capita GDP of each country. The sensitivity analysis performed in most studies was deterministic. The completeness of the report was considered sufficient in most of the items evaluated by CHEERS. The Dominance Interpretation (DRM) varied; in 6 studies, the HPV test was dominant, 5 studies showed a weak dominance evaluating greater effectiveness of the HPV test at a higher cost, yet in 2 studies conventional cytology was dominant. Although the context-dependent nature of economic evaluations, this review points out the challenge of methodological standardization in the analytical models.
Assuntos
Infecções por Papillomavirus , Neoplasias do Colo do Útero , Análise Custo-Benefício , DNA , Países em Desenvolvimento , Detecção Precoce de Câncer , Feminino , Humanos , Programas de RastreamentoRESUMO
Economic assessments are relevant to support the decision to incorporate more cost-effective strategies to reduce Cervical Cancer (CC) mortality. This systematic review analyzes the economic evaluation studies of CC prevention strategies (HPV DNA-based tests and conventional cytology) in low- and middle-income countries. Medline, EMBASE, CRD, and LILACS were searched for economic evaluation studies that reported cost and effectiveness measures of HPV DNA-based tests for CC screening and conventional cytology in women, without age, language, or publication date restrictions. Selection and data extraction were carried out independently. For comparability of results, cost-effectiveness measures were converted to international dollars (2019). Report quality was assessed using the CHEERS checklist. The Dominance Matrix Ranking (DRM) was used to analyze and interpret the results. The review included 15 studies from 12 countries, with cost-effectiveness analyzes from the health system's perspective and a 3% discount rate. The strategies varied in age and frequency of screening. Most studies used the Markov analytical model, and the cost-benefit threshold was based on the per capita GDP of each country. The sensitivity analysis performed in most studies was deterministic. The completeness of the report was considered sufficient in most of the items evaluated by CHEERS. The Dominance Interpretation (DRM) varied; in 6 studies, the HPV test was dominant, 5 studies showed a weak dominance evaluating greater effectiveness of the HPV test at a higher cost, yet in 2 studies conventional cytology was dominant. Although the context-dependent nature of economic evaluations, this review points out the challenge of methodological standardization in the analytical models.
RESUMO
Abstract Economic assessments are relevant to support the decision to incorporate more cost-effective strategies to reduce Cervical Cancer (CC) mortality. This systematic review analyzes the economic evaluation studies of CC prevention strategies (HPV DNA-based tests and conventional cytology) in low- and middle-income countries. Medline, EMBASE, CRD, and LILACS were searched for economic evaluation studies that reported cost and effectiveness measures of HPV DNA-based tests for CC screening and conventional cytology in women, without age, language, or publication date restrictions. Selection and data extraction were carried out independently. For comparability of results, cost-effectiveness measures were converted to international dollars (2019). Report quality was assessed using the CHEERS checklist. The Dominance Matrix Ranking (DRM) was used to analyze and interpret the results. The review included 15 studies from 12 countries, with cost-effectiveness analyzes from the health system's perspective and a 3% discount rate. The strategies varied in age and frequency of screening. Most studies used the Markov analytical model, and the cost-benefit threshold was based on the per capita GDP of each country. The sensitivity analysis performed in most studies was deterministic. The completeness of the report was considered sufficient in most of the items evaluated by CHEERS. The Dominance Interpretation (DRM) varied; in 6 studies, the HPV test was dominant, 5 studies showed a weak dominance evaluating greater effectiveness of the HPV test at a higher cost, yet in 2 studies conventional cytology was dominant. Although the context-dependent nature of economic evaluations, this review points out the challenge of methodological standardization in the analytical models.
RESUMO
This article aims to evaluate the association between the use of electronic cigarettes and initiation to smoking, through a systematic review with meta-analysis of longitudinal studies. A bibliographic search was performed on the MEDLINE, Embase, LILACS and PsycInfo databases. Reference selection, data extraction and risk of bias assessment of the studies were independently carried out in pairs, and the disagreements were discussed with a third researcher to reach a consensus. Meta-analysis was performed using the Mantel-Haenszel random effects model. Among the 25 studies included, 22 evaluated the outcome of conventional cigarette experimentation and nine assessed the outcome of current smoking (in the last 30 days). The meta-analysis showed that the use of electronic cigarettes increased the risk of conventional cigarette experimentation by almost three and a half times (RR=3.42; 95%CI 2.81-4.15), and by more than four times the risk of current smoking (RR=4.32; 95%CI 3.13-5.94). The risk of smoking initiation is significantly higher among electronic cigarette users. The marketing authorization of such devices may represent a threat to public health policies in Brazil.
O objetivo deste artigo é avaliar a associação entre uso de cigarros eletrônicos e iniciação ao tabagismo, por meio de uma revisão sistemática com meta-análise de estudos longitudinais. Busca bibliográfica foi realizada nas bases MEDLINE, Embase, LILACS e PsycInfo. As etapas de seleção de referências, extração dos dados e avaliação do risco de viés dos estudos foi realizada em dupla, de forma independente e as divergências discutidas com um terceiro pesquisador para obtenção de consenso. Meta-análise foi realizada por meio do modelo Mantel-Haenszel de efeitos aleatórios. Dentre os 25 estudos incluídos, 22 avaliaram o desfecho de experimentação de cigarro convencional e nove avaliaram o desfecho de tabagismo atual (nos últimos 30 dias). A meta-análise demonstrou que o uso de cigarro eletrônico aumentou em quase três vezes e meia o risco de experimentação de cigarro convencional (RR=3,42; IC95% 2,81-4,15) e em mais de quatro vezes o risco de tabagismo atual (RR=4,32; IC95% 3,13-5,94). O risco de iniciação ao tabagismo é significativamente maior entre usuários de cigarro eletrônico. A liberação da comercialização desses dispositivos pode representar uma ameaça para as políticas de saúde pública no Brasil.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Abandono do Hábito de Fumar , Produtos do Tabaco , Humanos , Fumar/epidemiologia , Prevenção do Hábito de FumarRESUMO
Resumo O objetivo deste artigo é avaliar a associação entre uso de cigarros eletrônicos e iniciação ao tabagismo, por meio de uma revisão sistemática com meta-análise de estudos longitudinais. Busca bibliográfica foi realizada nas bases MEDLINE, Embase, LILACS e PsycInfo. As etapas de seleção de referências, extração dos dados e avaliação do risco de viés dos estudos foi realizada em dupla, de forma independente e as divergências discutidas com um terceiro pesquisador para obtenção de consenso. Meta-análise foi realizada por meio do modelo Mantel-Haenszel de efeitos aleatórios. Dentre os 25 estudos incluídos, 22 avaliaram o desfecho de experimentação de cigarro convencional e nove avaliaram o desfecho de tabagismo atual (nos últimos 30 dias). A meta-análise demonstrou que o uso de cigarro eletrônico aumentou em quase três vezes e meia o risco de experimentação de cigarro convencional (RR=3,42; IC95% 2,81-4,15) e em mais de quatro vezes o risco de tabagismo atual (RR=4,32; IC95% 3,13-5,94). O risco de iniciação ao tabagismo é significativamente maior entre usuários de cigarro eletrônico. A liberação da comercialização desses dispositivos pode representar uma ameaça para as políticas de saúde pública no Brasil.
Abstract This article aims to evaluate the association between the use of electronic cigarettes and initiation to smoking, through a systematic review with meta-analysis of longitudinal studies. A bibliographic search was performed on the MEDLINE, Embase, LILACS and PsycInfo databases. Reference selection, data extraction and risk of bias assessment of the studies were independently carried out in pairs, and the disagreements were discussed with a third researcher to reach a consensus. Meta-analysis was performed using the Mantel-Haenszel random effects model. Among the 25 studies included, 22 evaluated the outcome of conventional cigarette experimentation and nine assessed the outcome of current smoking (in the last 30 days). The meta-analysis showed that the use of electronic cigarettes increased the risk of conventional cigarette experimentation by almost three and a half times (RR=3.42; 95%CI 2.81-4.15), and by more than four times the risk of current smoking (RR=4.32; 95%CI 3.13-5.94). The risk of smoking initiation is significantly higher among electronic cigarette users. The marketing authorization of such devices may represent a threat to public health policies in Brazil.
Assuntos
Humanos , Abandono do Hábito de Fumar , Produtos do Tabaco , Sistemas Eletrônicos de Liberação de Nicotina , Fumar/epidemiologia , Prevenção do Hábito de FumarRESUMO
Uma revisão sistemática da literatura incluiu trabalhos desenvolvidos em diferentes populações de todos os continentes do mundo sobre a relação entre padrões de consumo identificados por análise fatorial e câncer de mama. Foi verificado que os dados convergem para o consumo de um padrão alimentar composto por vegetais, frutas, peixes, crustáceos, soja e seus derivados, azeite, frango, e adicionalmente, para outro padrão que descreve o hábito alimentar típico da região estudada. Esses padrões atuariam reduzindo o risco da doença, enquanto um terceiro padrão caracterizado pelo consumo de bebidas alcoólicas estaria aumentando o risco.Para averiguar a existência de padrões semelhantes na população de mulheres brasileiras foram examinados dados do módulo de consumo alimentar individual medido pela POF 2008-2009, de uma subamostra de 8.325 mulheres não lactentes, não gestantes e com idade superior a 35 anos. Foram identificados por meio de Análise Fatorial Exploratória (AFE) quatro padrões alimentares, denominados Tradicional Brasileiro, Lanches. Gorduras e Álcool e Lacto-vegetariano. Em seguida, a população de 8.325 mulheres avaliadas foi reunida em seis grupos (clusters) segundo o padrão de consumo alimentar. (...) Com relação às características sociodemográficas da população avaliada os seis Grupos se apresentaram de forma similar com relação à distribuição pelas cinco regiões do país. Contudo, foram verificadas associações entre os Grupos e situação geográfica (urbano/rural) (...) Foi observada correlação inversa entre idade e escolaridade para essa população de mulheres brasileiras.
A systematic review of literature about the relationship between dietary patterns identified by factor analysis and breast cancer included studies carried out in different populations from all continents of the world. Were found a dietary pattern compound of vegetables, fruits, fish, shellfish, soy and soy derivatives, olive oil, chicken, and another dietary pattern that described the typical foods habits of the studied region. These dietary patterns seemed reduce the risk of breast cancer. A third dietary pattern characterized by consumption of alcoholic beverages seemed increasing the risk. To investigate the existence of similar patterns in Brazilian women were observed data of individual food intake module of the Brazilian household budget survey (2008-2009) in a subsample of 8,325 non-lactating, non-pregnant and aged over 35 years women. By Exploratory Factor Analysis (EFA) were identified four dietary patterns called Traditional Brazilian pattern, Snacks pattern, Fats and alcohol pattern and Lacto-vegetarian pattern. The subsample of 8,325 women was grouped in six clusters according to the four dietary pattern observed. Group 1 (n=974 women) was characterized by higher consumption of pattern Lacto-vegetarian pattern, Group 2 (n=2,904 women) presented the second highest standardized mean score for the consumption of Snacks pattern. Group 3 (n=1,629 women) presented the lowest average consumption of Traditional Brazilian pattern. In Group 4 (n=838 women) was observed the high standardized score for the consumption of Alcohol and fats pattern. Group 5 (n=1,209 women) showed the highest score for Snacks pattern and Group 6 (n=771 women) showed...
Assuntos
Humanos , Feminino , Neoplasias da Mama , Comportamento Alimentar/etnologia , Inquéritos sobre Dietas , Epidemiologia , Ingestão de Alimentos , Saúde da Mulher , Análise por Conglomerados , Análise FatorialRESUMO
O objetivo do presente trabalho foi descrever a associação entre hábitos alimentares durante a adolescência e a ocorrência de tumores cerebrais na idade adulta. Estudo caso-controle hospitalar foi conduzido na região metropolitana do Rio de Janeiro, Brasil. O consumo dietético foi estimado por um questionário de frequência alimentar (QFA). Padrões dietéticos foram determinados utilizando técnicas de componentes principais e análise fatorial. Quatro padrões dietéticos foram identificados e juntos explicaram 32,5% da variância total do modelo. Os resultados indicam que os padrões associados a menores chances de desenvolvimento de tumores cerebrais eram ricos em açúcares e gorduras (padrão lanches, OR=0,61; IC95% 0,37?1,00, e padrão gordura animal, OR=0,55; IC95% 0,32?0,94). Nenhuma associação significativa foi observada entre os padrões tradicional e misto. Os achados controversos desta análise não esclarecem o papel da dieta na adolescência sobre o desenvolvimento de tumores cerebrais em adultos.