Bakgrund: Palliativ vård betyder lindrande vård där döden ses som en normal och naturlig process. Det innebär att varken påskynda eller skjuta upp döden för patienten, samt att ge en god omvårdnad utifrån ett helhetsperspektiv. Omvårdnaden av patienter i livets slutskede på sjukhus kan vara påfrestande för sjuksköterskor. Syfte: Syftet med studien var att få ökad förståelse för sjuksköterskors upplevelser av att vårda patienter i livets slutskede på sjukhus. Metod: Metoden som användes var en litteraturöversikt där tretton artiklar analyserades. Resultat: Resultaten presenteras utifrån fyra kategorier; faktorer som bidrar till en god pallia-tiv vård, faktorer som påverkar sjuksköterskan negativt, kommunikationen ett viktigt verktyg och när dödsfallet är ett faktum samt tretton underkategorier. Sjuksköterskor upplevde att när de bidragit till en värdig död hade de lyckats i sin omvårdnad. Delar av den palliativa vården kan upplevas som berikande för sjuksköterskor, men den innebär också stora påfrestningar. Påfrestningarna ansågs kunna minskas med hjälp av mer tid, samt kunskap och utbildning inom palliativ vård. Konklusion: Sammanfattningsvis visade denna studie att sjuksköterskor har en viktig uppgift i samband med att vårda patienter livets slutskede, samt att många fakto-rer spelar in för att sjuksköterskor ska känna att de ger en god palliativ vård till patienter i livets slutskede. / Background: Palliative care means relieving care where death is seen as a normal and natural process. It means that either hurry up or postpone death for the patient, and to provide good health care from a holistic perspective. Nursing care of patients dying in hospital can be stressful for nurses. Purpose: The purpose with the study was to increase the understanding for nurses experiences of the caring for dying patients in hospital. Method: The used method was an systematic literature summary were thirteen articles has been analyzed. Result: The result is presented on the basis of four main category: factors that contribute to a good pallia-tive care, factors that affect nurses negatively, communication a major instrument and when death is a fact, together with thirteen subcategories. Nurses felt that when they contribute to a dignified death, they had succeded in their care. Parts of the palliative care feels rewarding for the nurses, but it also involve great strains. The strain was considered to be reduced by using more time, knowledge and training in palliative care. Conclusion: The study concludes that nurses has an important role in the care for dying patients, and many factors is involved when they provide a good palliative care.

Bakgrund: Palliativ vård betyder lindrande vård där döden ses som en normal och naturlig process. Det innebär att varken påskynda eller skjuta upp döden för patienten, samt att ge en god omvårdnad utifrån ett helhetsperspektiv. Omvårdnaden av patienter i livets slutskede på sjukhus kan vara påfrestande för sjuksköterskor. Syfte: Syftet med studien var att beskriva sjuksköterskors upplevelser av att vårda patienter i livets slutskede på sjukhus. Metod: Metoden som användes var en litteraturöversikt där tretton artiklar analyserades. Resultat: Resul-taten presenteras utifrån fyra kategorier; faktorer som bidrar till en god palliativ vård, faktorer som påverkar sjuksköterskan negativt, kommunikationen ett viktigt verktyg och när dödsfallet är ett faktum samt tretton underkategorier. Sjuksköterskor upplevde att när de bidragit till en värdig död hade de lyckats i sin omvårdnad. Delar av den palliativa vården kan upplevas som berikande för sjuksköterskor, men den innebär också stora påfrestningar. Påfrestningarna an-sågs kunna minskas med hjälp av mer tid, samt kunskap och utbildning inom palliativ vård. Konklusion: Sammanfattningsvis visade denna studie att sjuksköterskor har en viktig uppgift i samband med att vårda patienter livets slutskede, samt att många faktorer spelar in för att sjuksköterskor ska känna att de ger en god palliativ vård till patienter i livets slutskede. / Background: Palliative care means relieving care where death is seen as a normal and natural process. It means that either hurry up or postpone death for the patient, and to provide good health care from a holistic perspective. Nursing care of patients dying in hospital can be stressful for nurses. Purpose: The purpose with the study was to describe nurses experiences of the caring for dying patients in hospital. Method: The used method was an systematic lit-erature summary were thirteen articles has been analyzed. Result: The result is presented on the basis of four main category: factors that contribute to a good palliative care, factors that affect nurses negatively, communication a major instrument and when death is a fact, together with thirteen subcategories. Nurses felt that when they contribute to a dignified death, they had succeded in their care. Parts of the palliative care feels rewarding for the nurses, but it also involve great strains. The strain was considered to be reduced by using more time, knowledge and training in palliative care. Conclusion: The study concludes that nurses has an important role in the care for dying patients, and many factors is involved when they provide a good palliative care.

Opioid drug related death is the topic of this thesis. Each of the published works submitted in this volume has investigated an aspect of opioid drug related death. The publications have been grouped into three sub-themes: i. Characteristics of opioid drug related deaths ii. Methadone-related deaths in and out of treatment iii. Improving the quality of treatment for opioid drug dependence: a focus on injectable opioid treatment The introduction and background (Chapter1) will briefly review-the-relevant literature on opioid drug death predating my own contribution to the field. The next chapter of the thesis, 'Publications' (Chapter 2), will comprise the body of published work being submitted for the degree of Doctor of Medicine. Each article is accompanied by text on the preceding page outlining my individual contribution to that research study. The thesis will conclude with a discussion of the published works (Discussion, Chapter 3) which summarises the chief findings and reflects on the international significance and impact of the work. Finally, the Conclusion (Chapter 4) will submit suggestions for areas of future research into opioid drug related death.

Philosophiae Doctor - PhD / Globally, Employee Assistance Programme (EAP) has become the most effective workplace programme used to assist employees in the identification and resolution of performance and behavioural related problems. Employees, irrespective of the sector of employment are seen as the most valuable assets of any organization and therefore their wellness is as important as the organization itself. Employees' personal or work related problems may adversely affect their health as well as their productivity, thereby impeding the growth of an organization. It is for this reason that the EAP has increasingly become an important tool in addressing employees’ personal and work related challenges. Midwives as employees are prone to challenges such as maternal deaths at the workplace. They are more likely to undergo stressful situations for failing to meet the general goal of their profession, which, among others, include provision of adequate care for pregnant women until they safely deliver. These stressful conditions have negative effects on midwives' health, behaviour and productivity. However, there is no literature that has looked at how midwives in the Ashanti Region of Ghana are affected by maternal deaths and their coping mechanisms employed to address the effects of maternal deaths. Literature revealed that there is hardly any known work-related assistance programme designed to support Ghanaian midwives when faced with work-related challenges likely to affect their work-output. Hence, this study developed an appropriate EAP for midwives dealing with maternal deaths in Ghana based on the exploration and description of the effects of maternal death, coping mechanisms used and their experiences with the facility-based maternal death review (MDR). In order to meet the general aim of the study, a qualitative research approach, with a combination of exploratory, descriptive and contextual designs was used. Purposive sampling was employed to select participants; ward and unit managers (supervisors) (18) and midwives who met the inclusion criteria (39). A total of 57 participants were used in the study. Data were collected through semi-structured individual interviews and focus group discussions, as well as field notes. Thematic Content Analysis was used to manage data through transcribing, organizing, development of category and coding of data. Final data management was done with qualitative computer data analysis package (Atlas ti version 7.1.7). The full understanding of the effects of maternal deaths on midwives and the mechanisms of coping employed to address effects afforded the development of an EAP to support midwives dealing with maternal deaths. Five main themes emerged from the analysis of collected data, namely effect of death as a unique experience, multi-dimensional effects of MD on Midwives' personal life, effects of MD on the midwives’ associated environment, mechanisms of coping employed by Midwives and Perceived MDR process (Phase 1). Phase 2 considered the development of Employee Assistance Programme (EAP) for midwives dealing with maternal deaths in Ashanti Region of Ghana. The steps of developing occupational health service at the workplace by Acutt Hattingh and Bergh (2011) were applied to develop the EAP. Ethical practices pertaining to the study of human subjects as specified by the Research Ethics Committee of the University of the Western Cape and research guidelines of Ministry of Health- Ghana Health Service were observed. It is recommended that, all hospitals in Ashanti Region institute the EAP programme to assist midwives cope with challenges associated with maternal death.

Made available in DSpace on 2014-06-11T19:35:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-08-25Bitstream added on 2014-06-13T20:06:50Z : No. of bitstreams: 1 sleutjes_fcm_dr_botfm.pdf: 725660 bytes, checksum: 9a58cee8a9d2137fdcb115679023885d (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Investigar os óbitos neonatais pode ser uma importante estratégia para redução da mortalidade infantil e fetal, pois contribui para melhorar a qualidade da informação sobre esse evento adverso e possibilita a adoção, pelos serviços de saúde, de medidas para a prevenção de óbitos evitáveis. Objetivo Geral: avaliar os óbitos neonatais investigados no Departamento Regional de Saúde VI – Bauru, considerando-se os Colegiados de Gestão Regional, no ano de 2009. Metodologia: estudo descritivo e transversal, que analisou 162 óbitos investigados, a partir das informações digitadas no Sistema de Informações sobre Mortalidade Neonatal (SIM-Neo). Os resultados são apresentados de forma descritiva e a partir de escore síntese que considerou a qualidade da atenção ao pré-natal, ao parto e ao recém-nascido; fatores de risco pré-natal, no parto e com relação ao recém-nascido e situação sociodemográfica materna. Para análise dos escores foi ajustado um modelo para proporções do tipo logístico, considerando Colegiados e categorias como efeitos principais e a interação Colegiados versus categorias. Resultados: passaram por alguma investigação 88,5% dos óbitos ocorridos e 67,3% tiveram investigação completa. A análise dos escores relativos à qualidade da atenção pré-natal evidenciou diferença quando se consideraram os piores resultados (escore menores que cinco), sendo o Colegiado Vale do Jurumirim diferente e melhor que o de Bauru e o de Lins. Com relação à qualidade da assistência ao parto, houve diferença quando se compararam os Colegiados Vale do Jurumirim, Bauru e Cuesta Botucatu com Lins, sendo pior a situação de Lins. Para a qualidade da atenção ao neonato, os Colegiados de Bauru e Jaú diferiram e foram melhores que o Vale do Jurumirim. Quanto ao risco do neonato, o Colegiado Vale do Jurumirim... / Introduction: Investigating neonatal deaths can be an important strategy to reduce child and fetal mortality as it contributes to improve the quality of information on such adverse event and allows for the adoption of measures for prevention of evitable deaths by health care services. Objective: To evaluate neonatal deaths investigated at the Regional Health Department VI (DRS VI) – Bauru by taking into account the Regional Management Collegiates in 2009. Methodology: This is a descriptive crosssectional study that analyzed 162 deaths investigated from the information entered on the Neonatal Mortality Information System (SIM-Neo). Results are presented in a descriptive fashion and based on a synthesis score which considered the quality of prenatal care, the care to delivery and the care to newborns; prenatal risk factors, delivery risks and those related to newborns as well as maternal sociodemographic conditions. For score analysis, a logistic model was fitted for proportions by taking into account Collegiates and categories as main effects and the Collegiate-versuscategory interaction. Results: 88.5% of the occurring deaths underwent some investigation, and 67.3% were completely investigated. The analysis of the scores related to the quality of prenatal care showed difference when the worse scores (scores lower than five) were considered, and Vale do Jurumirim Collegiate was different and better than those in Bauru and Lins. As regards the quality of care to delivery, difference was found when comparing the Collegiates in Vale do Jurumirim, Bauru and Cuesta Botucatu with that in Lins, and Lins showed the worst situation. As for the quality of care to neonates, the Collegiates in Bauru and Jau differed and were better than that in Vale do Jurumirim. Concerning risk to neonates, the Collegiate... (Complete abstract click electronic access below)

Orientador: Cristina Maria Garcia de Lima Parada / Banca: Maria Antonieta de Barros Leite Carvalhaes / Banca: Luana Carandina / Banca: Marilisa Barros / Banca: Maria José Clapis / Resumo: Investigar os óbitos neonatais pode ser uma importante estratégia para redução da mortalidade infantil e fetal, pois contribui para melhorar a qualidade da informação sobre esse evento adverso e possibilita a adoção, pelos serviços de saúde, de medidas para a prevenção de óbitos evitáveis. Objetivo Geral: avaliar os óbitos neonatais investigados no Departamento Regional de Saúde VI - Bauru, considerando-se os Colegiados de Gestão Regional, no ano de 2009. Metodologia: estudo descritivo e transversal, que analisou 162 óbitos investigados, a partir das informações digitadas no Sistema de Informações sobre Mortalidade Neonatal (SIM-Neo). Os resultados são apresentados de forma descritiva e a partir de escore síntese que considerou a qualidade da atenção ao pré-natal, ao parto e ao recém-nascido; fatores de risco pré-natal, no parto e com relação ao recém-nascido e situação sociodemográfica materna. Para análise dos escores foi ajustado um modelo para proporções do tipo logístico, considerando Colegiados e categorias como efeitos principais e a interação Colegiados versus categorias. Resultados: passaram por alguma investigação 88,5% dos óbitos ocorridos e 67,3% tiveram investigação completa. A análise dos escores relativos à qualidade da atenção pré-natal evidenciou diferença quando se consideraram os piores resultados (escore menores que cinco), sendo o Colegiado Vale do Jurumirim diferente e melhor que o de Bauru e o de Lins. Com relação à qualidade da assistência ao parto, houve diferença quando se compararam os Colegiados Vale do Jurumirim, Bauru e Cuesta Botucatu com Lins, sendo pior a situação de Lins. Para a qualidade da atenção ao neonato, os Colegiados de Bauru e Jaú diferiram e foram melhores que o Vale do Jurumirim. Quanto ao risco do neonato, o Colegiado Vale do Jurumirim... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Investigating neonatal deaths can be an important strategy to reduce child and fetal mortality as it contributes to improve the quality of information on such adverse event and allows for the adoption of measures for prevention of evitable deaths by health care services. Objective: To evaluate neonatal deaths investigated at the Regional Health Department VI (DRS VI) - Bauru by taking into account the Regional Management Collegiates in 2009. Methodology: This is a descriptive crosssectional study that analyzed 162 deaths investigated from the information entered on the Neonatal Mortality Information System (SIM-Neo). Results are presented in a descriptive fashion and based on a synthesis score which considered the quality of prenatal care, the care to delivery and the care to newborns; prenatal risk factors, delivery risks and those related to newborns as well as maternal sociodemographic conditions. For score analysis, a logistic model was fitted for proportions by taking into account Collegiates and categories as main effects and the Collegiate-versuscategory interaction. Results: 88.5% of the occurring deaths underwent some investigation, and 67.3% were completely investigated. The analysis of the scores related to the quality of prenatal care showed difference when the worse scores (scores lower than five) were considered, and Vale do Jurumirim Collegiate was different and better than those in Bauru and Lins. As regards the quality of care to delivery, difference was found when comparing the Collegiates in Vale do Jurumirim, Bauru and Cuesta Botucatu with that in Lins, and Lins showed the worst situation. As for the quality of care to neonates, the Collegiates in Bauru and Jau differed and were better than that in Vale do Jurumirim. Concerning risk to neonates, the Collegiate... (Complete abstract click electronic access below) / Doutor

Orientador: Maria Coleta de Oliviera / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Filosofia e Ciencias Humanas / Made available in DSpace on 2018-08-12T20:50:38Z (GMT). No. of bitstreams: 1 Romio_JackelineAparecidaFerreira_M.pdf: 901995 bytes, checksum: 44af158f3981ec8b281dba05f7dbcee0 (MD5) Previous issue date: 2009 / Resumo: A pesquisa teve como objetivo estudar as formas de violência urbana e doméstica contra a mulher através da análise das mortes por agressão/homicídios, assim como as possíveis conexões, similaridades e diferenças de raça/cor nestes óbitos. Utilizamos dois tipos de fonte de dados de mortalidade: as Declarações de Óbito (SIM/MS) de 2000 a 2005 e os Boletins de Ocorrência (INFOCRIM/SSP-SP) de 2005. Para as informações sobre o perfil da população exposta ao risco de morte foram utilizados o Censo Demográfico 2000, de responsabilidade do IBGE e as projeções populacionais elaboradas pelo SEADE. A unidade espacial de análise foi o Município de São Paulo. Com este estudo demonstramos que as causas externas são a primeira causa de morte entre homens e mulheres da faixa de 15 a 24 anos; as agressões dentre as causas externas também é a principal causa de morte nesta faixa etária; a violência urbana também é detectada na morte feminina por homicídio, detectamos diferencias de raça/cor em todas as análises / Abstract: The objective of this research was to study the urban and domestic ways of violence against the woman, through deaths for aggression/homicides analysis, as well as the possible connections, similarities and differences of race/color of these deaths. We use two types of sources of mortality data: the Declarations of Death (SIM/MS), between 2000 to 2005, and Occurrence Reports (INFOCRIM/SSP-SP), 2005. The Demographic Census of 2000 and the population projections elaborated by the SEADE were used for information about the population exposed at risk of death profile. The space unit of analysis is the City of São Paulo. With this study we demonstrate that the external causes are the first cause of death between men and women of the age 15 to 24 years; the homicide amongst the xi external causes also are the main causes of death in this age group; the urban violence also is detected in the feminine death by homicide, we detected differentiates according to racein all analyses data / Mestrado / Demografia / Mestre em Demografia

O humor vítreo (HV) é um gel aquoso, transparente e incolor, situado entre o cristalino e a retina. Ele pode ser uma ferramenta para determinação de drogas de abuso, sobretudo quando é impossível fazer a determinação em sangue devido à sua ausência ou sua deterioração, por exemplo em casos de exsanguinação, embalsamento e carbonização. As drogas e seus metabólitos passam para o HV por difusão passiva e, de modo geral, a concentração dos analitos no HV é similar às concentrações obtidas no sangue. A cocaína e a benzoilecgonina são facilmente detectadas na matriz. Por outro lado, a difusão da morfina é bem limitada. O maior interesse do estudo de opioides é a análise de 6-acetilmorfina, que pode diferenciar o uso de heroína e morfina. O delta-9-tetrahidrocanabinol é uma molécula muito polar e fortemente ligada a proteínas plasmáticas, o que limita a sua difusão para o HV. Entre as anfetaminas, a metilenodioximetanfetamina e a metanfetamina são as moléculas mais estudadas no HV. Foi desenvolvido e validado um método utilizando GC-MS para análise simultânea de cocaína, anfetaminas, opioides, canabinoides e respectivos metabólitos em HV. Os analitos de interesse foram extraídos do HV utilizando extração em fase sólida e analisadas por GC-MS, utilizando o modo de aquisição SIM. A faixa de linearidade foi de 10 a 1000 ng/mL para todos os analitos, com exceção do éster de metilanidroecgonina (10 a 750 ng/mL). A exatidão variou de 95,6 a 104,0%, a precisão inter-ensaio variou de 1,2 a 10,0% e a precisão intra-ensaio foi menor que 10,4% para todos os analitos. O limite de quantificação para todas as drogas foi de 10 ng/mL e a recuperação variou de 70,4 a 100,1% para compostos básicos e neutros, entretanto os compostos ácidos apresentaram baixa recuperação - menor que 40%. A dosagem de etanol foi realizada por GC-FID e extração por headspace. Os métodos validados foram aplicados em 250 amostras de HV coletadas de vítimas de morte violentas nos anos de 2011 e 2012 que foram necropsiadas no Departamento Médico Legal de Vitória - ES. A maioria das vítimas era do sexo masculino (85,4%) e a causa mais comum de morte foi homicídio (46,2%), destes, 89,5% foram mortos por disparo de arma de fogo. Os acidentes de trânsito corresponderam a 44,1%; suicídio, 2,4%; e outras mortes totalizaram 7,2% das amostras. Substâncias psicoativas (álcool e drogas) foram positivas em 60,4% dos casos. Em 23,2% das amostras foi quantificada cocaína e/ou seu metabólito, e em um terço destes foi identificado o uso de crack. O álcool estava presente em 19,2% dos casos e a associação entre cocaína e álcool em 12,8% dos casos. Outras drogas incluíram anfetaminas (13 casos) e codeína (1 caso). Quando comparadas as concentrações das drogas pesquisadas no sangue e HV, a anfetamina e metanfetamina mostraram boa correlação entre as duas matrizes. A 6-acetilmorfina encontrada no HV foi utilizada para demonstrar o uso de heroína, uma vez que as concentrações foram mais altas do que no sangue. Entretanto, o HV não pode ser utilizado como amostra alternativa para detecção de canabinoides. / Vitreous humor is the aqueous gel located between the lens and retina. Vitreous humor is a useful alternative postmortem matrix for the detection of drugs, particularly in death investigations where postmortem blood is not available or is of limited quality or quantity (e.g. after hemorrhagic shock, burns, embalming or decomposition processes). Drugs and their metabolites enter the vitreous humor by passive diffusion from blood across the blood-vitreous barrier. Vitreous humor concentrations are often similar to the drug concentrations in the circulation blood. Cocaine and benzoylecgonine are easily detected in this matrix. On the order hand, morphine diffusion is limited. The interest in opiates is due to 6-acetylmorphine, which is stable in vitreous humor and can confirm heroin abuse. Drugs that are highly protein-bound, such as THC, achieve lower vitreous humor concentrations as only the free fraction can cross the blood-vitreous barrier. Methamphetamine and methylenodioxymetamphetamine are also detected in vitreous humor. A GC-MS method for simultaneous analysis of cocaine, amphetamines, opiates, cannabinoids and its metabolites in vitreous humor was developed and fully validated. Vitreous humor samples were extracted using solid phase extraction and analyzed by GC-MS in SIM mode. For all analytes the linearity ranged from 10 to 1000 ng/mL, excepted for anydroecgonine methylester which ranged from 10 to 750 ng/mL. Inter-assay imprecision ranged from 1.2 to 10.0% and intra-assay imprecision was less than 10.4% for all analytes at all QC concentrations. Accuracy ranged from 95.6 to 104.0% and recoveries ranging from 70.4 - 100.1% for basic and neutral compounds, the acids compounds had poor recovery (less than 40%). The limits of detection were up to 1.0 ng/mL. Ethanol was quantified by headspace extraction and GC-FID. The validated methodology was applied to 250 vitreous humor samples collected from violent death victims between 2011 and 2012 in the Departamento Médico Legal de Vitória - ES. Most of the victims were male (85.4%) and the most common cause of death was homicide (46.2%), in which 89.5 occurred by firearm shot. Traffic accident represented 44.1%, suicide 2.4% and other deaths 7.2%. Psychoactive substances (alcohol and?or drugs of abuse) were positive in 60.4% of the cases. Cocaine was quantified in 23.2% of the samples and one third was positive for crack cocaine. Ethanol was present in 19.2% of the cases and the association between cocaine and alcohol in 12.8%. Other drugs included amphetamines (13 cases) and codeine (1 case). When comparing the drug concentrations in blood and vitreous humor, amphetamine and methamphetamine showed a good correlation. 6-acetylmorphine in vitreous humor can demonstrate heroine abuse and its concentration is higher in vitreous humor than in blood. However, vitreous humor is not a good matrix for the detection of cannabinoids.

Os óbitos de mulheres em idade reprodutiva correspondem a 16% do total de óbitos femininos em todo o Brasil, indicando a dificuldade dos serviços de saúde em implementar ações baseadas na atenção integral à saúde da mulher no Sistema Único de Saúde, sob o enfoque ampliado da assistência, incorporando a perspectiva de gênero. Objetivo: analisar óbitos de mulheres em idade reprodutiva, residentes em Ribeirão Preto-SP, no período de 2007 a 2009, com ênfase nas causas de morte. Método: foram analisadas 532 Declarações de Óbito (DO) de mulheres de 10 a 49 anos residentes no município de Ribeirão Preto/SP que foram a óbito no período de 2007 a 2009, obtidas por meio do Comitê Municipal de Prevenção da Mortalidade Materna para transcrição integral dos dados. As mortes foram classificadas em maternas declaradas, não maternas e presumíveis. Procedeu-se com a análise dos dados com o software STATA, codificação das causas de acordo com a CID 10 e seleção da causa básica de óbito. Resultados: Os principais grupos de causas de morte foram: neoplasias 137 (26%), doenças do aparelho circulatório 94 (18%), doenças infecciosas e parasitárias 67 (13%) e causas externas 65 (12%). As mortes por causas maternas representaram a antepenúltima causa de óbito. Foram identificadas, após análise dos campos preenchidos na DO, 467 (88%) mortes não maternas, 5 (1%) mortes maternas declaradas e 60 (11%) mortes maternas presumíveis. Conclusão: O padrão de mortalidade do município é semelhante ao do país, apontando a necessidade de incrementar ações nas três esferas de governo voltadas para a saúde da população feminina. Conhecer o perfil de mortalidade de mulheres em idade reprodutiva possibilita a compreensão de suas principais demandas e problemas de saúde oferecendo subsídios para o planejamento de ações focadas em reduzir mortes por causas evitáveis. / The deaths of women in reproductive age represent 16% of all female deaths in Brazil, indicating the difficulty of health services to implement actions based on comprehensive health care of women in the National Health System, under the approach extended care, incorporating a gender perspective. Objective: To analyze deaths of women in reproductive age residing in Ribeirao Preto-SP, in the period of 2007 to 2009, focusing on causes of death. Method: We analyzed 532 Death Certificates of women aged 10 to 49 years residing in Ribeirao Preto - SP who died in the period 2007 to 2009, obtained through the Municipal Committee for the Prevention of Maternal Mortality for transcription full of data. The deaths were classified as declared maternal, not maternal and presumed. Proceeded with the analysis of the data with STATA software, coding causes according to ICD 10 and selecting the underlying cause of death. Results: The main groups of causes of death were neoplasms 137 (26%), circulatory diseases 94 (18%), infectious and parasitic diseases 67 (13%) and external causes 65 (12%). Deaths from maternal causes represented the antepenultimate cause of death. Were identified after analysis of the fields filled in Death Certificates, 467 (88%) not maternal deaths, 5 (1%) declared maternal and 60 (11%) presumed maternal deaths. Conclusion: The pattern of mortality in the municipality is similar to the country, pointing to the need for increased action in the three spheres of government focused on the health of the female population. Knowing the profile of women mortality in reproductive age furthers our understanding of their main demands and health problems, offering support for the planning of actions focused on reducing deaths from preventable causes.

La leucémie myéloïde chronique (LMC) est un syndrome myéloprolifératif lié à l’acquisition d’une anomalie chromosomique t(9;22) conduisant à l’expression d’une protéine de fusion p210 Bcr-Abl dont l’activité tyrosine kinase dérégulée est nécessaire et suffisante pour engendrer la maladie.Cette pathologie bénéficie depuis 2002 d’une avancée thérapeutique : les inhibiteurs de tyrosine kinase (ITK). Cette thérapeutique dite ciblée, dont le chef de file est l’imatinib, est très efficace puisque 80% des patients entre en rémission. Malheureusement, 20% des patients traités développent des résistances primaires ou secondaires, dépendantes ou non de l’oncogène Bcr-Abl dont certaines ont été caractérisées. A ce titre, la LMC est devenue un modèle d’étude à la fois des mécanismes oncogéniques mais aussi des résistances.La résistance aux ITK dans la LMC peut être considérée sur deux plans. D’une part la résistance qui permet à la cellule leucémique d’échapper à la pression thérapeutique des ITK et d’autre part la résistance « intrinsèque » de la cellule souche leucémique par des mécanismes certainement multiples. Ce second niveau de résistance est à l’origine de la récurrence de la LMC lors de l’arrêt du traitement.Cette thèse a consisté à déterminer comment pouvait mourir les cellules de LMC en réponse aux ITK pour mettre en évidence les morts induites et les régulations qui existent entre-elles. De plus, cela a permis d’utiliser les morts non-apoptotiques pour contourner les mécanismes de résistance aux ITK.Nous avons montré pour la première fois en utilisant différents modèles cellulaires de LMC (cellules K562, Lama-84 et AR-230), que l’imatinib (ainsi que les autres ITK nilotinib et dasatinib) induit de la sénescence en plus d’une réponse apoptotique. En absence d’apoptose, par inhibition de cette dernière, la réponse sénescente devient une réponse majeure des cellules de LMC suggérant que l’apoptose a un rôle de « frein » sur la sénescence. L’autophagie activée par les ITK régule négativement la réponse apoptotique alors qu’elle est nécessaire pour une réponse sénescente majeure. Nous avons pu mettre en évidence deux types de sénescences induites par l’imatinib : une sénescence dépendante et une indépendante de l’autophagie. L’autophagie semble donc au cœur de la régulation des morts cellulaires. Puisque les cellules de LMC peuvent mourir par des morts non-apoptotiques, nous avons cherché à éliminer les cellules résistantes par des morts non-apoptotiques. Pour cela différentes molécules ont été utilisées telles que l’acide mycophénolique (MPA), un immunosuppresseur déjà utilisé en clinique. Le MPA en inhibant la synthèse de GTP permet d’induire des dommages à l’ADN et une réponse apoptotique et/ou sénescente. Dans ce contexte, l’autophagie protège la cellule de la réponse apoptotique mais ne protège pas la cellule de la sénescence. Le MPA est au contraire un puissant inducteur d’apoptose sur les cellules primaires. En effet, il induit une apoptose massive des cellules primaires résistantes aux ITK quelque soit le mécanisme impliqué (surexpression de tyrosine kinase, mutation de Bcr-Abl). Le MPA est l’exemple parfait des molécules qu’il nous faut rechercher pour éliminer les cellules résistantes de LMC notamment dans le cas où les patients sont en crise blastique et donc résistants aux thérapeutiques.Ces résultats suggèrent que la sénescence est une des morts qui peut être induite pour dépasser la résistance des cellules cancéreuses. / Chronic Myeloid Leukemia is a myeloproliferative syndrome connected to the acquisition of a chromosomal abnormality t(9;22) leading to the expression of a fusion protein p210 Bcr-Abl of whom the tyrosine kinase activity deregulated is necessary and sufficient to engender the disease.This pathology benefits since 2002 of a therapeutic advance: the tyrosine kinase inhibitors (TKI). This targeted therapeutics, from which imatinib is the front-line, is very effective because 80 % of patients enters in remission. However, 20 % of the treated patients develop primary or secondary resistances which can be dependent or not to the Bcr-Abl oncogene among which some have been characterized. Indeed, CML is now a model to study both oncogenic and resistances mechanisms.Resistance to TKI in CML can be considered on two sides. On one hand the resistance allowing the leukemic cell to escape the therapeutic pressure of TKI and on a second hand the “intrinsic” resistance of Leukemic stem cells by multiple mechanisms. This second level of resistance is at the origin of the CML recurrence.This thesis consisted in determining how could die the CML cells in response to TKI to bring to light cell deaths induced and the regulations existing between them. Furthermore, it allowed exploring the use of non-apoptotic cell deaths to overcome resistance to TKI.We showed for the first time by using CML cell lines (K562, Lama-84 and AR-230), that imatinib (as well as nilotinib and dasatinib) induced senescence besides an apoptotic response. In absence of apoptosis, by its inhibition, senescence becomes a major response of CML cells suggesting that apoptosis is limiting senescence. Autophagy activated by TKI negatively regulates apoptosis while it is necessary for a major senescent response. We were able to bring to light two types of senescence in response to TKI : a senescence dependent and a senescence independent of autophagy suggesting it plays a critical role in cell death regulation.Because CML cells can die by non-apoptotic cell deaths, we used them to eliminate TKI resistant cells. Mycophenolic acid (MPA), an immonusuppressor already used in therapeutic as an immunosuppressive agent has been extensively used. MPA by inhibiting the synthesis of GTP induces DNA damage and apoptotic and\or senescent response. In this context, autophagy protects the cells from apoptotic response but do not from senescence. Conversely, MPA is a powerful inductor of apoptosis on hematopoietic primary cells. Indeed, it induces apoptosis of TKI resistant primary cells whatever the mechanism involved (overexpression of tyrosine kinases or mutation of Bcr-Abl). MPA illustrates the need to look for new molecules to eliminate TKI resistant CML cells, particularly when patients are in the evolved blastic phase of the disease.These results suggest that senescence is one of the deaths which can be used to overcome resistance of cancer cells.