DNA damage in circulating leukocytes measured with the comet assay may predict the risk of death.

The comet assay or single cell gel electrophoresis, is the most common method used to measure strand breaks and a variety of other DNA lesions in human populations. To estimate the risk of overall mortality, mortality by cause, and cancer incidence associated to DNA damage, a cohort of 2,403 healthy individuals (25,978 person-years) screened in 16 laboratories using the comet assay between 1996 and 2016 was followed-up. Kaplan-Meier analysis indicated a worse overall survival in the medium and high tertile of DNA damage (p < 0.001). The effect of DNA damage on survival was modelled according to Cox proportional hazard regression model. The adjusted hazard ratio (HR) was 1.42 (1.06-1.90) for overall mortality, and 1.94 (1.04-3.59) for diseases of the circulatory system in subjects with the highest tertile of DNA damage. The findings of this study provide epidemiological evidence encouraging the implementation of the comet assay in preventive strategies for non-communicable diseases.

Reduction of inequities of access to appropriate childbirth care in Rede Cegonha. / Redução das iniquidades sociais no acesso às tecnologias apropriadas ao parto na Rede Cegonha.

This article compares the findings of "Avaliação da Rede Cegonha" (ARC - Stork Network Assessment), an evaluative study on the Rede Cegonha (RC - Stork Network) program, with Nascer no Brasil (NB - Born in Brazil), a national survey on labor and birth, conducted in 2011-12, before the start implementation of RC. ARC was conducted in 2017, in 606 maternity hospitals involved in RC and NB included a sample with national representation of 266 hospitals. In the current analysis, we included the 136 SUS hospitals that participated in both studies, totaling 3,790 and 12,227 puerperal women. We perform comparisons of best practices and interventions in the management of labor and delivery using Pearson's chi-square test for independent samples. The prevalence of best practices was, on average, 150% higher in ARC than in NB, with a greater relative increase in less developed regions, for older, brown and black women and less educated. Regarding interventions, there was an average reduction of 30% between NB and ARC, with a greater relative reduction in less developed regions and less educated women. There was a significant improvement in the scenario of care for labor and childbirth, with a reduction in regional, educational and racial inequalities in access to appropriate technologies, suggesting that the RC intervention was effective.

Este artigo compara os achados da Avaliação da Rede Cegonha (ARC), estudo avaliativo sobre o programa Rede Cegonha (RC), com o Nascer no Brasil (NB), inquérito nacional sobre parto e nascimento, realizado em 2011-12, antes do início da implementação da RC. A ARC foi conduzida em 2017, em 606 maternidades envolvidas na RC e o NB e empregou uma amostra com representatividade nacional de 266 hospitais. Na análise atual, incluímos os 136 hospitais do SUS que participaram de ambos os estudos, totalizando 3.790 e 12.227 puérperas, respectivamente. Realizamos as comparações de boas práticas e intervenções no manejo do trabalho de parto e de parto utilizando o teste qui-quadrado para amostras independentes. A prevalência das boas práticas foi, em média, 150% maior na ARC que no NB, com maior aumento relativo nas regiões menos desenvolvidas, para mulheres mais velhas, pardas e pretas e menos escolarizadas. Com relação às intervenções, houve redução média de 30% entre o NB e a ARC, com maior redução relativa nas regiões menos desenvolvidas e nas mulheres menos escolarizadas. Houve melhoria significativa no cenário da atenção ao trabalho de parto e parto, com diminuição de iniquidades regionais, de nível de instrução e raciais no acesso às tecnologias apropriadas, sugerindo que a intervenção da RC foi efetiva.

Redução das iniquidades sociais no acesso às tecnologias apropriadas ao parto na Rede Cegonha / Reduction of inequities of access to appropriate childbirth care in Rede Cegonha

Resumo Este artigo compara os achados da Avaliação da Rede Cegonha (ARC), estudo avaliativo sobre o programa Rede Cegonha (RC), com o Nascer no Brasil (NB), inquérito nacional sobre parto e nascimento, realizado em 2011-12, antes do início da implementação da RC. A ARC foi conduzida em 2017, em 606 maternidades envolvidas na RC e o NB e empregou uma amostra com representatividade nacional de 266 hospitais. Na análise atual, incluímos os 136 hospitais do SUS que participaram de ambos os estudos, totalizando 3.790 e 12.227 puérperas, respectivamente. Realizamos as comparações de boas práticas e intervenções no manejo do trabalho de parto e de parto utilizando o teste qui-quadrado para amostras independentes. A prevalência das boas práticas foi, em média, 150% maior na ARC que no NB, com maior aumento relativo nas regiões menos desenvolvidas, para mulheres mais velhas, pardas e pretas e menos escolarizadas. Com relação às intervenções, houve redução média de 30% entre o NB e a ARC, com maior redução relativa nas regiões menos desenvolvidas e nas mulheres menos escolarizadas. Houve melhoria significativa no cenário da atenção ao trabalho de parto e parto, com diminuição de iniquidades regionais, de nível de instrução e raciais no acesso às tecnologias apropriadas, sugerindo que a intervenção da RC foi efetiva.

Abstract This article compares the findings of "Avaliação da Rede Cegonha" (ARC - Stork Network Assessment), an evaluative study on the Rede Cegonha (RC - Stork Network) program, with Nascer no Brasil (NB - Born in Brazil), a national survey on labor and birth, conducted in 2011-12, before the start implementation of RC. ARC was conducted in 2017, in 606 maternity hospitals involved in RC and NB included a sample with national representation of 266 hospitals. In the current analysis, we included the 136 SUS hospitals that participated in both studies, totaling 3,790 and 12,227 puerperal women. We perform comparisons of best practices and interventions in the management of labor and delivery using Pearson's chi-square test for independent samples. The prevalence of best practices was, on average, 150% higher in ARC than in NB, with a greater relative increase in less developed regions, for older, brown and black women and less educated. Regarding interventions, there was an average reduction of 30% between NB and ARC, with a greater relative reduction in less developed regions and less educated women. There was a significant improvement in the scenario of care for labor and childbirth, with a reduction in regional, educational and racial inequalities in access to appropriate technologies, suggesting that the RC intervention was effective.

[Implementation of the National Childbirth Guidelines in Brazil: barriers and trategiesObstáculos y estrategias para la aplicación de las Directrices Nacionales para el Parto Normal en el Brasil]. / Barreiras e estratégias para implementação de Diretrizes Nacionais do Parto Normal no Brasil.

The present report describes the process and results obtained with a knowledge translation project developed in three stages to identify barriers to the National Childbirth Guidelines in Brazil as well strategies for effective implementation. The Improving Programme Implementation through Embedded Research (iPIER) model and the Supporting Policy Relevant Reviews and Trials (SUPPORT) tools provided the methodological framework for the project. In the first stage, the quality of the Guidelines was evaluated and the barriers preventing implementation of the recommendations were identified through review of the global evidence and analysis of contributions obtained in a public consultation process. In the second stage, an evidence synthesis was used as basis for a deliberative dialogue aimed at prioritizing the barriers identified. Finally, a second evidence synthesis was presented in a new deliberative dialogue to discuss six options to address the prioritized barriers: 1) promote the use of multifaceted interventions; 2) promote educational interventions for the adoption of guidelines; 3) perform audits and provide feedback to adjust professional practice; 4) use reminders to mediate the interaction between workers and service users; 5) enable patient-mediated interventions; and 6) engage opinion leaders to promote the use of guidelines. The processes and results associated with each stage were documented and formulated to inform a review and update of the Guidelines and the development of an implementation plan for the recommendations. An effective implementation of the Guidelines is relevant to improve the care provided during labor and childbirth in Brazil.

En este informe se presentan los procesos y resultados de un proyecto de traducción de conocimiento desarrollado en tres etapas para identificar los obstáculos y las estrategias para la aplicación efectiva de las Directrices Nacionales para el Parto Normal en el Brasil. El marco metodológico adoptado comprendió la iniciativa iPIER (Improving Program Implementation through Embedded Research) y las herramientas SUPPORT para políticas basadas en evidencia. En la primera etapa se evaluó la calidad de las Directrices y se identificaron los obstáculos a la aplicación de las recomendaciones, teniendo en cuenta la evidencia mundial y el análisis de las contribuciones obtenidas mediante una consulta pública. En la segunda etapa, una síntesis de la evidencia sirvió de base para un diálogo deliberativo para la priorización de los obstáculos. Por último, una nueva síntesis de la evidencia sirvió de base para un segundo diálogo deliberativo y presentó seis opciones para hacer frente a los obstáculos priorizados: 1) fomentar el uso de estrategias de intervención polifacéticas; 2) promover intervenciones educativas para mejorar el uso de directrices sanitarias; 3) realizar auditorías y proporcionar retroalimentación para la adecuación de la práctica profesional; 4) utilizar recordatorios para mediar en la interacción entre profesionales y usuarios; 5) permitir intervenciones mediadas por el paciente; y 6) incluir a líderes de opinión para fomentar el uso de directrices sanitarias. Se documentaron y presentaron los procesos y resultados de cada etapa del proyecto para fundamentar la actualización de las Directrices y la elaboración de un plan de aplicación de las recomendaciones. La aplicación efectiva de las Directrices es importante para mejorar la atención del parto y el nacimiento en el Brasil.

Implementation of national childbirth guidelines in Brazil: barriers and strategies

[ABSTRACT]. The present report describes the process and results obtained with a knowledge translation project developed in three stages to identify barriers to the Implementation of the National Guidelines for Normal Childbirth in Brazil, as well strategies for effective implementation. The Improving Programme Implementation through Embedded Research (iPIER) model and the Supporting Policy Relevant Reviews and Trials (SUPPORT) tools provided the methodological framework for the project. In the first stage, the quality of the Guidelines was evaluated and the barriers preventing implementation of the recommendations were identified through review of the global evidence and analysis of contributions obtained in a public consultation process. In the second stage, an evidence synthesis was used as the basis for a deliberative dialogue aimed at prioritizing the barriers identified. Finally, a second evidence synthesis was presented in a new deliberative dialogue to discuss six options to address the prioritized barriers: 1) promote the use of multifaceted interventions; 2) promote educational interventions for the adoption of guidelines; 3) perform audits and provide feedback to adjust professional practice; 4) use reminders to mediate the interaction between workers and service users; 5) enable patient-mediated interventions; and 6) engage opinion leaders to promote use of the Guidelines. The processes and results associated with each stage were documented and formulated to inform a review and update of the Guidelines and the development of an implementation plan for the recommendations. Effective implementation of the Guidelines is important for improving the care provided during labor and childbirth in Brazil.

[RESUMEN]. En este informe se presentan los procesos y resultados de un proyecto de traducción de conocimiento desarrollado en tres etapas para identificar los obstáculos y las estrategias para la aplicación efectiva de las Directrices Nacionales para el Parto Normal en el Brasil. El marco metodológico adoptado comprendió la iniciativa iPIER (Improving Program Implementation through Embedded Research) y las herramientas SUPPORT para políticas basadas en evidencia. En la primera etapa se evaluó la calidad de las Directrices y se identificaron los obstáculos a la aplicación de las recomendaciones, teniendo en cuenta la evidencia mundial y el análisis de las contribuciones obtenidas mediante una consulta pública. En la segunda etapa, una síntesis de la evidencia sirvió de base para un diálogo deliberativo para la priorización de los obstáculos. Por último, una nueva síntesis de la evidencia sirvió de base para un segundo diálogo deliberativo y presentó seis opciones para hacer frente a los obstáculos priorizados: 1) fomentar el uso de estrategias de intervención polifacéticas; 2) promover intervenciones educativas para mejorar el uso de directrices sanitarias; 3) realizar auditorías y proporcionar retroalimentación para la adecuación de la práctica profesional; 4) utilizar recordatorios para mediar en la interacción entre profesionales y usuarios; 5) permitir intervenciones mediadas por el paciente; y 6) incluir a líderes de opinión para fomentar el uso de directrices sanitarias. Se documentaron y presentaron los procesos y resultados de cada etapa del proyecto para fundamentar la actualización de las Directrices y la elaboración de un plan de aplicación de las recomendaciones. La aplicación efectiva de las Directrices es importante para mejorar la atención del parto y el nacimiento en el Brasil.

Barreiras e estratégias para implementação de Diretrizes Nacionais do Parto Normal no Brasil

[RESUMO]. Este relato apresenta os processos e resultados de um projeto de tradução do conhecimento desenvolvido em três etapas para identificar barreiras e estratégias para a efetiva implementação das Diretrizes Nacionais do Parto Normal no Brasil. O referencial metodológico adotado foi o da iniciativa iPIER e das ferramentas SUPPORT para Políticas Informadas por Evidências. Na primeira etapa, a qualidade das Diretrizes foi avaliada e as barreiras à implementação das recomendações foram identificadas, considerando evidências globais e análise de contribuições de uma consulta pública. Na segunda etapa, uma síntese de evidências informou um diálogo deliberativo para priorização de barreiras. Por fim, uma nova síntese de evidências informou um segundo diálogo deliberativo e apresentou seis opções para abordar as barreiras priorizadas: 1) incentivar o uso de estratégias de intervenção multifacetadas; 2) promover intervenções educativas para o uso de diretrizes em saúde; 3) realizar auditoria e feedback para adequação da prática profissional; 4) utilizar lembretes para mediar a interação entre profissionais e usuários; 5) viabilizar intervenções mediadas por pacientes e 6) incluir líderes de opinião para incentivar o uso de diretrizes em saúde. Os processos e resultados de cada etapa do projeto foram documentados e apresentados para informar a atualização das Diretrizes e o desenvolvimento de plano de implementação das recomendações. A efetiva implementação das Diretrizes é relevante para a melhoria da atenção ao parto e nascimento no Brasil.

[ABSTRACT]. The present report describes the process and results obtained with a knowledge translation project developed in three stages to identify barriers to the National Childbirth Guidelines in Brazil as well strategies for effective implementation. The Improving Programme Implementation through Embedded Research (iPIER) model and the Supporting Policy Relevant Reviews and Trials (SUPPORT) tools provided the methodological framework for the project. In the first stage, the quality of the Guidelines was evaluated and the barriers preventing implementation of the recommendations were identified through review of the global evidence and analysis of contributions obtained in a public consultation process. In the second stage, an evidence synthesis was used as basis for a deliberative dialogue aimed at prioritizing the barriers identified. Finally, a second evidence synthesis was presented in a new deliberative dialogue to discuss six options to address the prioritized barriers: 1) promote the use of multifaceted interventions; 2) promote educational interventions for the adoption of guidelines; 3) perform audits and provide feedback to adjust professional practice; 4) use reminders to mediate the interaction between workers and service users; 5) enable patient-mediated interventions; and 6) engage opinion leaders to promote the use of guidelines. The processes and results associated with each stage were documented and formulated to inform a review and update of the Guidelines and the development of an implementation plan for the recommendations. An effective implementation of the Guidelines is relevant to improve the care provided during labor and childbirth in Brazil.

[RESUMEN]. En este informe se presentan los procesos y resultados de un proyecto de traducción de conocimiento desarrollado en tres etapas para identificar los obstáculos y las estrategias para la aplicación efectiva de las Directrices Nacionales para el Parto Normal en el Brasil. El marco metodológico adoptado comprendió la iniciativa iPIER (Improving Program Implementation through Embedded Research) y las herramientas SUPPORT para políticas basadas en evidencia. En la primera etapa se evaluó la calidad de las Directrices y se identificaron los obstáculos a la aplicación de las recomendaciones, teniendo en cuenta la evidencia mundial y el análisis de las contribuciones obtenidas mediante una consulta pública. En la segunda etapa, una síntesis de la evidencia sirvió de base para un diálogo deliberativo para la priorización de los obstáculos. Por último, una nueva síntesis de la evidencia sirvió de base para un segundo diálogo deliberativo y presentó seis opciones para hacer frente a los obstáculos priorizados: 1) fomentar el uso de estrategias de intervención polifacéticas; 2) promover intervenciones educativas para mejorar el uso de directrices sanitarias; 3) realizar auditorías y proporcionar retroalimentación para la adecuación de la práctica profesional; 4) utilizar recordatorios para mediar en la interacción entre profesionales y usuarios; 5) permitir intervenciones mediadas por el paciente; y 6) incluir a líderes de opinión para fomentar el uso de directrices sanitarias. Se documentaron y presentaron los procesos y resultados de cada etapa del proyecto para fundamentar la actualización de las Directrices y la elaboración de un plan de aplicación de las recomendaciones. La aplicación efectiva de las Directrices es importante para mejorar la atención del parto y el nacimiento en el Brasil.

Chromatographic Detection of 8-Hydroxy-2'-Deoxyguanosine in Leukocytes of Asbestos Exposed Workers for Assessing Past and Recent Carcinogen Exposures.

Asbestos fibers include a group of silicate minerals that occur in the environment and are widely employed in occupational settings. Asbestos exposure has been associated to various chronic diseases; such as pulmonary fibrosis; mesothelioma; and lung cancer; often characterized by a long period of latency. Underlying mechanisms that are behind the carcinogenic effect of asbestos have not been fully clarified. Therefore; we have conducted an epidemiological study to evaluate the relationship between 8-hydroxy-2'-deoxyguanosine (8-oxodG), one of the most reliable biomarkers of oxidative stress and oxidative DNA damage; and asbestos exposure in the peripheral blood of residents in Tuscany and Liguria regions; Italy; stratified by occupational exposure to this carcinogen. Levels of 8-oxodG were expressed such as relative adduct labeling (RAL); the frequency of 8-oxodG per 105 deoxyguanosine was significantly higher among exposed workers with respect to the controls; i.e., 3.0 ± 0.2 Standard Error (SE) in asbestos workers versus a value of 1.3 ± 0.1 (SE) in unexposed controls (p < 0.001). When the relationship with occupational history was investigated; significant higher levels of 8-oxodG were measured in current and former asbestos workers vs. healthy controls; 3.1 ± 0.3 (SE) and 2.9 ± 0.2 (SE), respectively. After stratification for occupational history; a significant 194% excess of adducts was found in workers with 10 or more years of past asbestos exposure (p < 0.001). 8-oxodG can be used for medical surveillance programs of cohorts of workers with past and recent exposures to carcinogens for the identification of subjects requiring a more intense clinical surveillance.

Application of the comet assay in human biomonitoring: An hCOMET perspective.

The comet assay is a well-accepted biomonitoring tool to examine the effect of dietary, lifestyle, environmental and occupational exposure on levels of DNA damage in human cells. With such a wide range of determinants for DNA damage levels, it becomes challenging to deal with confounding and certain factors are inter-related (e.g. poor nutritional intake may correlate with smoking status). This review describes the effect of intrinsic (i.e. sex, age, tobacco smoking, occupational exposure and obesity) and extrinsic (season, environmental exposures, diet, physical activity and alcohol consumption) factors on the level of DNA damage measured by the standard or enzyme-modified comet assay. Although each factor influences at least one comet assay endpoint, the collective evidence does not indicate single factors have a large impact. Thus, controlling for confounding may be necessary in a biomonitoring study, but none of the factors is strong enough to be regarded a priori as a confounder. Controlling for confounding in the comet assay requires a case-by-case approach. Inter-laboratory variation in levels of DNA damage and to some extent also reproducibility in biomonitoring studies are issues that have haunted the users of the comet assay for years. Procedures to collect specimens, and their storage, are not standardized. Likewise, statistical issues related to both sample-size calculation (before sampling of specimens) and statistical analysis of the results vary between studies. This review gives guidance to statistical analysis of the typically complex exposure, co-variate, and effect relationships in human biomonitoring studies.

Implementation of national childbirth guidelines in Brazil: barriers and strategies.

The present report describes the process and results obtained with a knowledge translation project developed in three stages to identify barriers to the Implementation of the National Guidelines for Normal Childbirth in Brazil, as well strategies for effective implementation. The Improving Programme Implementation through Embedded Research (iPIER) model and the Supporting Policy Relevant Reviews and Trials (SUPPORT) tools provided the methodological framework for the project. In the first stage, the quality of the Guidelines was evaluated and the barriers preventing implementation of the recommendations were identified through review of the global evidence and analysis of contributions obtained in a public consultation process. In the second stage, an evidence synthesis was used as the basis for a deliberative dialogue aimed at prioritizing the barriers identified. Finally, a second evidence synthesis was presented in a new deliberative dialogue to discuss six options to address the prioritized barriers: 1) promote the use of multifaceted interventions; 2) promote educational interventions for the adoption of guidelines; 3) perform audits and provide feedback to adjust professional practice; 4) use reminders to mediate the interaction between workers and service users; 5) enable patient-mediated interventions; and 6) engage opinion leaders to promote use of the Guidelines. The processes and results associated with each stage were documented and formulated to inform a review and update of the Guidelines and the development of an implementation plan for the recommendations. Effective implementation of the Guidelines is important for improving the care provided during labor and childbirth in Brazil.

En este informe se presentan los procesos y resultados de un proyecto de traducción de conocimiento desarrollado en tres etapas para identificar los obstáculos y las estrategias para la aplicación efectiva de las Directrices Nacionales para el Parto Normal en el Brasil. El marco metodológico adoptado comprendió la iniciativa iPIER (Improving Program Implementation through Embedded Research) y las herramientas SUPPORT para políticas basadas en evidencia. En la primera etapa se evaluó la calidad de las Directrices y se identificaron los obstáculos a la aplicación de las recomendaciones, teniendo en cuenta la evidencia mundial y el análisis de las contribuciones obtenidas mediante una consulta pública. En la segunda etapa, una síntesis de la evidencia sirvió de base para un diálogo deliberativo para la priorización de los obstáculos. Por último, una nueva síntesis de la evidencia sirvió de base para un segundo diálogo deliberativo y presentó seis opciones para hacer frente a los obstáculos priorizados: 1) fomentar el uso de estrategias de intervención polifacéticas; 2) promover intervenciones educativas para mejorar el uso de directrices sanitarias; 3) realizar auditorías y proporcionar retroalimentación para la adecuación de la práctica profesional; 4) utilizar recordatorios para mediar en la interacción entre profesionales y usuarios; 5) permitir intervenciones mediadas por el paciente; y 6) incluir a líderes de opinión para fomentar el uso de directrices sanitarias. Se documentaron y presentaron los procesos y resultados de cada etapa del proyecto para fundamentar la actualización de las Directrices y la elaboración de un plan de aplicación de las recomendaciones. La aplicación efectiva de las Directrices es importante para mejorar la atención del parto y el nacimiento en el Brasil.

Barreiras e estratégias para implementação de Diretrizes Nacionais do Parto Normal no Brasil / Implementation of the National Childbirth Guidelines in Brazil: barriers and strategies

Este relato apresenta os processos e resultados de um projeto de tradução do conhecimento desenvolvido em três etapas para identificar barreiras e estratégias para a efetiva implementação das Diretrizes Nacionais do Parto Normal no Brasil. O referencial metodológico adotado foi o da iniciativa iPIER e das ferramentas SUPPORT para Políticas Informadas por Evidências. Na primeira etapa, a qualidade das Diretrizes foi avaliada e as barreiras à implementação das recomendações foram identificadas, considerando evidências globais e análise de contribuições de uma consulta pública. Na segunda etapa, uma síntese de evidências informou um diálogo deliberativo para priorização de barreiras. Por fim, uma nova síntese de evidências informou um segundo diálogo deliberativo e apresentou seis opções para abordar as barreiras priorizadas: 1) incentivar o uso de estratégias de intervenção multifacetadas; 2) promover intervenções educativas para o uso de diretrizes em saúde; 3) realizar auditoria e feedback para adequação da prática profissional; 4) utilizar lembretes para mediar a interação entre profissionais e usuários; 5) viabilizar intervenções mediadas por pacientes e 6) incluir líderes de opinião para incentivar o uso de diretrizes em saúde. Os processos e resultados de cada etapa do projeto foram documentados e apresentados para informar a atualização das Diretrizes e o desenvolvimento de plano de implementação das recomendações. A efetiva implementação das Diretrizes é relevante para a melhoria da atenção ao parto e nascimento no Brasil.

Implementation of national childbirth guidelines in Brazil: barriers and strategies

O presente relatório descreve o processo e os resultados obtidos com um projeto de tradução do conhecimento desenvolvido em três etapas para identificar barreiras à Implementação das Diretrizes Nacionais para o Parto Normal no Brasil, bem como estratégias para sua efetiva implementação. O modelo Improving Program Implementation through Embedded Research (iPIER) e as ferramentas de Supporting Policy Relevant Reviews and Trials (SUPPORT) forneceram a estrutura metodológica para o projeto. Na primeira etapa, a qualidade das Diretrizes foi avaliada e as barreiras que impediram a implementação das recomendações foram identificadas por meio da revisão das evidências globais e da análise das contribuições obtidas em um processo de consulta pública. Na segunda fase, uma síntese de evidências foi utilizada como base para um diálogo deliberativo visando priorizar as barreiras identificadas. Finalmente, uma segunda síntese de evidências foi apresentada em um novo diálogo deliberativo para discutir seis opções para abordar as barreiras priorizadas: 1) promover o uso de intervenções multifacetadas; 2) promover intervenções educativas para a adoção de diretrizes; 3) realizar auditorias e fornecer feedback para ajustar a prática profissional; 4) usar lembretes para mediar a interação entre trabalhadores e usuários do serviço; 5) permitir intervenções mediadas pelo paciente; e 6) envolver formadores de opinião para promover o uso das Diretrizes. Os processos e resultados associados a cada etapa foram documentados e formulados para informar uma revisão e atualização das Diretrizes e o desenvolvimento de um plano de implementação para as recomendações.

Breast Cancer and Exposure to Organochlorines in the CECILE Study: Associations with Plasma Levels Measured at the Time of Diagnosis and Estimated during Adolescence.

Exposure to environmental chemicals with hormonal effects, such as organochlorine compounds (OCs), during developmental periods of breast cells may have an impact on the incidence of breast cancer later in life. However, the assessment of exposure to these chemicals that occurred in early life at the time of breast cancer development in adult women is a difficult challenge in epidemiological studies. Plasma levels of the OCs p,p'-dichlorodiphenyl dichloroethene (DDE) and polychlorinated biphenyl congener 153 (PCB153) were measured in 695 cases and 1055 controls of a population-based case-control study conducted in France (CECILE study). Based on these values, we used a physiologically-based pharmacokinetic (PBPK) model to estimate PCB153 levels at age 11⁻20 years when the women were adolescents. Overall, there was no clear association between breast cancer risk and measured levels of DDE and PCB153 at the time of diagnosis, but there was a trend of decreasing odds ratios of breast cancer with increasing DDE and PCB153 levels in women aged 50 years and over. The PBPK model revealed that PCB153 concentrations estimated during adolescence were highest in the youngest women born after 1960 who reached adolescence at a time when environmental contamination was maximum, and very low in the oldest women who attained adolescence before the contamination peak. Negative associations between breast cancer and PCB153 estimates during adolescence were also found. The negative associations between DDE and PCB153 levels measured at the time of diagnosis or estimated during adolescence in our study were unexplained. Further investigations are needed to clarify whether this finding is real or related to study artifacts. However, this study suggests that using PBPK models in epidemiological studies to back-estimate OC exposures during early life stages may be useful to address critical questions on cancer development.

Gene and protein expression of CXCR4 in adult and elderly patients with chronic rhinitis, pharyngitis or sinusitis undergoing thermal water nasal inhalations.

BACKGROUND: Chronic rhinitis, pharyngitis and sinusitis are common health problems with a significant impact on public health, and are suspected to be influenced by ageing factors. Nasal inhalation with thermal water may be used to reduce symptoms, inflammation and drug intake. A pre-post clinical study was conducted in 183 consecutive adult and elderly patients with chronic rhinitis, pharyngitis or sinusitis, to evaluate whether thermal water nasal inhalations could improve their symptoms, clinical signs and rhinomanometry measurements, and influence inflammatory biomarkers levels in nasal epithelial cells. RESULTS: Participants profile revealed that they were aged on average (mean age and SD 60.6 ± 15.2 years, median 65, range 20-86, 86 aged ≤ 65 years (47%), 96 aged > 65 years (53%)) and extremely concerned about wellbeing. Older age was associated with better compliance to inhalation treatment. Total symptom and clinical evaluation scores were significantly ameliorated after treatment (p < 0.001), with no substantial difference according to age, while rhinomanometry results were inconsistent. Persistence of symptom improvement was confirmed at phone follow up 1 year later (n = 74). The training set of 48 inflammatory genes (40 patients) revealed a strong increase of CXCR4 gene expression after nasal inhalations, confirmed both in the validation set (143 patients; 1.2 ± 0.68 vs 3.3 ± 1.2; p < 0.0001) and by evaluation of CXCR4 protein expression (40 patients; 1.0 ± 0.39 vs 2.6 ± 0.66; p < 0.0001). CXCR4 expression was consistently changed in patients with rhinitis, pharyngitis or sinusitis. The increase was smaller in current smokers compared to non-smokers. Results were substantially unchanged when comparing aged subjects (≥ 65 years) or the eldest quartile (≥ 71 years) to the others. Other genes showed weaker variations (e.g. FLT1 was reduced only in patients with sinusitis). CONCLUSIONS: These results confirm the clinical impact of thermal water nasal inhalations on upper respiratory diseases both in adults and elders, and emphasize the role of genes activating tissue repair and inflammatory pathways. Future studies should evaluate CXCR4 as possible therapeutic target or response predictor in patients with chronic rhinitis, pharyngitis or sinusitis. TRIAL REGISTRATION: Communication to Italian Ministry of Health - ICPOM 000461. Registered 10/11/2014.

DNA damage and genomic instability among workers formerly and currently exposed to asbestos.

Objectives Despite an asbestos ban in the European Union, exposure to asbestos still represents an occupational risk. Biomarkers of DNA damage and genomic instability in groups exposed to asbestos may contribute to the identification of subgroups/subjects at higher risk. Methods A cross-sectional study was conducted on 468 male individuals (80 working in occupational settings with potential exposure to asbestos fibers, 202 retired workers with past exposure, and 186 non-exposed controls) to compare genomic instability, cell proliferation and differentiation level using the non-invasive micronucleus buccal cytome assay. Data on demographic variables, lifestyle, and occupational history were collected with a standardized questionnaire. Micronuclei (MN) and other biomarkers of DNA damage and genomic instability were scored in a minimum of 2000/1000 cells per individual, respectively. Results Univariate and multivariate analysis showed opposite associations of MN frequency with current and former exposure. Compared to unexposed controls, workers with current potential exposure to asbestos had 55% lower MN frequency [95% confidence interval (CI) 71-29%, P<0.001] while those with past exposure had 34% higher MN frequency (95% CI 1-77%, P<0.001). The frequency of cells with condensed chromatin and binucleated cells was elevated among formerly exposed workers. The multivariate analysis did not reveal any actual confounders, although lower MN frequency was observed among subjects eating fresh fruit or vegetables every day or taking vitamin supplements. Conclusions Active workers with potential exposure to asbestos fibers did not show increased genomic damage. On the contrary, workers exposed in the past experienced a persistently elevated genomic instability, which may be used for risk assessment at subgroup or individual level.

Occupational exposure to organic solvents and risk of male breast cancer: a European multicenter case-control study.

Objectives The etiology of male breast cancer (MBC) is largely unknown but a causal role of exposure to organic solvents has been suggested. Previous studies on occupational risk factors of breast cancer were often restricted to women who are frequently exposed to lower levels and at a lower frequency than men. We investigated the association between MBC and occupational exposure to petroleum and oxygenated and chlorinated solvents in a multicenter case-control study of rare cancers in Europe. Methods The study included 104 MBC cases and 1901 controls. Detailed lifetime work history was obtained during interviews, together with sociodemographic characteristics, medical history and lifestyle factors. Occupational exposures to solvents were estimated from a job-exposure matrix. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated using unconditional logistic regression models. Results Lifetime cumulative exposure to trichloroethylene >23.9 ppm years was associated with an increased MBC risk, compared to non-exposure [OR (95% CI): 2.1 (1.2-4.0); P trend <0.01). This increase in risk persisted when only exposures that occurred ≥10 years before diagnosis were considered. In addition, a possible role for benzene and ethylene glycol in MBC risk was suggested, but no exposure-response trend was observed. Conclusions These findings add to the evidence of an increased risk of breast cancer among men professionally exposed to trichloroethylene and possibly to benzene or ethylene glycol. Further studies should be conducted in populations with high level of exposure to confirm our results.

Occupational exposure to textile dust and lung cancer risk: Results from the ICARE Study.

BACKGROUND: To investigate the association of lung cancer with occupational exposure to textile dust and specifically to cotton dust in the population-based case-control study ICARE. METHODS: Lifelong occupational history of 2926 cases and 3555 controls was collected using standardized questionnaires, with specific questions for textile dust exposure. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated using unconditional logistic regression models controlling for confounding factors including smoking and asbestos exposure. RESULTS: An inverse association between textile dust exposure and lung cancer was found among workers exposed ≥5% of their work time (OR = 0.80, 95%CI = 0.58-1.09), more pronounced for distant exposures (40+ years; up to a 56% reduced risk, statistically significant). The OR of lung cancer was significantly decreased among workers exposed to cotton fibers (OR = 0.70, 95%CI = 0.48-0.97). CONCLUSIONS: Our results provide some evidence of a decreased risk of lung cancer associated with exposure to textile dust, particularly cotton.

Occupational exposure to endotoxins and lung cancer risk: results of the ICARE Study.

OBJECTIVES: To investigate the role of occupational exposure to endotoxins in lung cancer in a French population-based case-control study (ICARE (Investigation of occupational and environmental causes of respiratory cancers)). METHODS: Detailed information was collected on the occupational history and smoking habits from 2926 patients with histologically confirmed lung cancer and 3555 matched controls. We evaluated each subject's endotoxin exposure after cross referencing International Standard Classification of Occupations (ISCO) codes (for job tasks) and Nomenclature d'Activités Françaises (NAF) codes (for activity sectors). Endotoxin exposure levels were attributed to each work environment based on literature reports. ORs and 95% CIs were estimated using unconditional logistic regression models and controlled for main confounding factors. RESULTS: An inverse association between exposure to endotoxins and lung cancer was found (OR=0.80, 95% CI 0.66 to 0.95). Negative trends were shown with duration and cumulative exposure, and the risk was decreased decades after exposure cessation (all statistically significant). Lung cancer risk was particularly reduced among workers highly exposed (eg, in dairy, cattle, poultry, pig farms), but also in those weakly exposed (eg, in waste treatment). Statistically significant interactions were shown with smoking, and never/light smokers were more sensitive to an endotoxin effect than heavy smokers (eg, OR=0.14, 95% CI 0.06 to 0.32 and OR=0.80, 95% CI 0.45 to 1.40, respectively, for the quartiles with the highest cumulative exposure, compared with those never exposed). Pronounced inverse associations were shown with adenocarcinoma histological subtype (OR=0.37, 95% CI 0.25 to 0.55 in the highly exposed). CONCLUSIONS: Our findings suggest that exposure to endotoxins, even at a low level, reduces the risk of lung cancer.

Menstrual and reproductive factors and lung cancer risk: A pooled analysis from the international lung cancer consortium.

Many clinical features of lung cancer are different in women and men. Sex steroid hormones exert effects in nonreproductive organs, such as the lungs. The association between menstrual and childbearing factors and the risk of lung cancer among women is still debated. We performed a pooled analysis of eight studies contributing to the International Lung Cancer Consortium (4,386 cases and 4,177 controls). Pooled associations between menstrual or reproductive factors and lung cancer were estimated using multivariable unconditional logistic regression. Subgroup analyses were done for menopause status, smoking habits and histology. We found no strong support for an association of age at menarche and at menopause with lung cancer, but peri/postmenopausal women were at higher risk compared to premenopausal (OR 1.47, 95% CI 1.11-1.93). Premenopausal women showed increased risks associated with parity (OR 1.74, 95% CI 1.03-2.93) and number of children (OR 2.88, 95% CI 1.21-6.93 for more than 3 children; p for trend 0.01) and decreased with breastfeeding (OR 0.54, 95% CI 0.30-0.98). In contrast, peri/postmenopausal subjects had ORs around unity for the same exposures. No major effect modification was exerted by smoking status or cancer histology. Menstrual and reproductive factors may play a role in the genesis of lung cancer, yet the mechanisms are unclear, and smoking remains the most important modifiable risk factor. More investigations in large well-designed studies are needed to confirm these findings and to clarify the underlying mechanisms of gender differences in lung cancer risk.