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Les initiatives internationales pour l’accès au traitement antirétroviral (ARV) ont permis une réduction de la morbi-mortalité liée au VIH. Parallèlement, il existe croissance des risques cardio vasculaire (FRCV) dans les pays en développement, témoin d’une transition épidémiologique. Notre objectif était d’évaluer l’importance des FRCV avant et après mise sous antirétroviraux chez des personnes infectées par le VIH en Afrique. L’essai Temprano avait pour objectif d’évaluer les bénéfices et risque du traitement antirétroviral précoce et d’une chimio prophylaxie par 6 mois d’isoniazide (IPT) après 30 mois de suivi. Cette étude a conclu à l’efficacité des 2 interventions sur la réduction de la morbidité sévère, conduisant l’OMS, dès 2015, à recommander les ARV dès que les CD4 sont inférieurs à 500 CD4/mm3. Dans ce travail, nous avons évalué la prévalence des FRCV, et en particulier l’importance de l’obésité et du surpoids, à l’inclusion puis après 24 mois d’ARV. Nous avons ensuite calculé le score de risque cardio vasculaire selon l’équation de Framingham, avec et sans lipides à l’inclusion et à la fin du suivi. Il existait(i) une bonne corrélation des 2 équations (ii) une augmentation plus marquée du risque cardiovasculaire chez les femmes et (iii) une absence de différence de l’augmentation du risque selon les stratégies thérapeutiques. Enfin, dans le suivi long terme de Temprano nous montrons une efficacité de l’IPT sur la réduction de la mortalité, ce qui apporte un espoir dans un contexte où, malgré la transition épidémiologique en cours, les causes de mortalité sont toujours dominées par la Tuberculose en Afrique sub-saharienne. / The international initiatives for promoting access to antiretroviral therapy (ART) have reduced HIV- related morbidity and mortality. Meanwhile, there are growing cardiovascular risk factors (CVRF) in developing countries, which are witnessing an epidemiological transition. Our objective was to assess the significance of CVRF before and after initiating antiretroviral therapy in HIV-infected people in Africa. Temprano trial aimed to assess the benefits and risks of early antiretroviral therapy and 6-month isoniazid preventive therapy (IPT) after 30-month follow-up. This study concluded that both interventions are effective to reduce severe morbidity, what led WHO, in 2015, to recommend starting ART immediately if CD4 count drop below 500 cells / mm3. In this study, we assessed the prevalence of CVRF and the significance of obesity and overweight at baseline and after 24 months of ART in particular. We then assess the cardiovascular risk score according to the Framingham equation, with and without lipids, at baseline and at the end of follow-up. There were: (i) a positive correlation between the 2 equations (ii) a sharper increase in cardiovascular risks among women and (iii) no difference in the risk increase according to treatment strategies. Finally, in the long-term follow-up of Temprano trial, we are showing the efficacy of IPT on the reduction of mortality, which brings hope in a context where, despite the on-going epidemiological transition, the causes of deaths are still dominated by Tuberculosis in sub- Saharan Africa.

With the hectic time of today, the number of people with cardio-vascular disorder increases continuously. A whole range of factors are the cause of this disorder. Among others, it is stress which people are mostly exposed to, due to the modern bustling style of life. Further, it is improper food, obesity, diabetes mellitus, smoking and many other reasons increasing the risk of this illness. In connection with cardio {--} vascular disorder, the patients may be confronted with the decision, whether to undergo a cardiac {--} surgery operation or not. The patients quite understandably go a whole range of emotions, anxiety and feelings in connection with the cardio-surgery operation. In our thesis, we determined 3 aims. In the first aim, we concentrated our attention on the cardio-surgery patient´s perceiving him himself, his family and his future in connection with the cardio-surgery operation. The aim was carried out. Four hypotheses refer to this aim. Hypothesis number 1: The cardio-surgery patient perceives the cardio-surgery operation as the result of his life style. Hypothesis number 2: After the heart operation, the cardio-surgery patient feels to have failed in the eye of his family. Hypothesis number 3: The psychic wellbeing of the cardio-surgery patient depends on the help and assistance of his family (background) during the time of his convalescence. Hypothesis number 4: The cardio-surgery patient believes to be able to join in a normal life, the same as before his health problem leading to the cardio-surgery operation has started. The second aim has to do with the most frequent anxieties the cardio-surgery patient must cope with in connection with the heart operation. The aim was carried out. To this aim, the hypothesis number 5 related: Highly specialized nursing care of a cardio-surgery patient is concentrated on the most frequent anxieties of these patients. The third aim was directed at non-saturated needs of the cardio-surgery patient during the time of his hospitalization after the operation. To this aim, the hypothesis number 6 applied: In the nursing care of a cardio-surgery patient, the problems arising from dissatisfying the psychic needs prevail over dissatisfying the basic needs. The dates for the purpose of the research examination were collected in the form of an anonymous questionnaire consisting of 32 questions. The question used here were both opened and closed. The questionnaires were given to hospitalized patients before and after the heart operation in 6 cardio-centers. The research complex was produced by 185 respondents. The results were graphically worked into column graphs and tables. In the research examination, 4 of 6 hypotheses were confirmed. The results of this work will be applicable with the work of the nurses at the cardio-surgery for the purpose of improving the nursing care of cardio-surgery patients.

Le cancer et les maladies cardiovasculaires sont deux problèmes de santé majeurs. Les survivants du cancer ont un risque plus élevé de développer et de mourir d'une maladie cardiovasculaire par rapport à la population générale. De même, les patients atteints de maladies cardiovasculaires sont également plus susceptibles de recevoir un diagnostic de cancer. Bien que les deux conditions partagent de nombreux facteurs de risque, le cancer et les maladies cardiovasculaires ont traditionnellement été étudiés séparément. Récemment, une vague de recherches en cours a mis en évidence des points communs biologiques entre le cancer et les maladies cardiovasculaires. Ces découvertes ont été rendues possibles grâce à des avancées scientifiques importantes, notamment la caractérisation moléculaire élargie des modulateurs de l'inflammation, l'élucidation des structures du protéasome et de l'inflammasome, ainsi que des contributions visant à renforcer nos connaissances sur l'immunité cellulaire. Grâce à ces avancées, il est désormais possible d'obtenir des informations précieuses sur les circuits complexes de la réponse immunitaire innée et adaptative, ainsi que sur les mécanismes de défense de l'hôte. Les progrès notables réalisés dans ces domaines ont posé les bases solides de la biologie de l'inflammation. L'application des principes appris dans ce domaine à la maladie humaine n'a que récemment commencé à donner des résultats fructueux, conduisant à la croissance exponentielle du domaine de l'inflammation dans le cancer et les maladies cardiovasculaires. Pour le cancer comme pour les maladies cardiovasculaires, l'immunomodulation est récemment apparue comme un facteur clé dans leur traitement et leur prise en charge. Avec le temps, il est également devenu évident que cibler une voie inflammatoire particulière pour traiter une condition peut avoir des implications importantes pour l'autre, reflétant l'interaction complexe entre ces deux processus pathologiques. Les avancées réalisées ont permis de reconnaître que l'inflammation joue un rôle actif dans le développement et la progression physiopathologique du cancer et des maladies cardiovasculaires. Toutefois, la compréhension de l'inflammation sur le cancer et les maladies cardiovasculaires est en constante évolution, et des recherches en cours sont nécessaires pour découvrir de nouvelles informations sur les mécanismes complexes de leurs relations. Dans ce contexte, nous avons entrepris des analyses distinctes pour approfondir notre compréhension et contribuer aux efforts de recherche innovants en cours, afin de réduire le fardeau croissant du cancer et des maladies cardiovasculaires. Premièrement, nous avons effectué une méta-analyse génétique sur le risque de cancer incident chez les patients atteints de maladie coronarienne prenant des statines. Dans cette étude, nous avons pu identifier et répliquer une variation génétique associée à un risque plus élevé de diagnostic incident de cancer chez les femmes utilisatrices de statines. La variation génétique se trouvait dans la région de l'antigène leucocytaire humain qui est largement responsable de l'activation des lymphocytes T et de la régulation des réponses immunitaires. Ces résultats réitèrent l'implication active des processus inflammatoires sous-jacents à la maladie coronarienne et au cancer. Deuxièmement, nous avons cherché à explorer l'effet de l'hématopoïèse clonale, une condition dans laquelle certaines cellules sanguines sont produites à partir d'une seule cellule mutée plutôt qu'à partir de processus normaux de production de cellules sanguines, sur le risque de décès par causes cardiovasculaires chez les patients diagnostiqués avec un cancer en utilisant une grande cohorte prospective. Dans une première analyse, nos résultats ont montré que les porteurs de modifications chromosomiques en mosaïque, un type distinct d'hématopoïèse clonale, présentaient un risque plus élevé de décès par maladie coronarienne que les non-porteurs. Dans une analyse de suivi, nos résultats ont montré que les porteurs d'hématopoïèse clonale de potentiel indéterminé étaient plus susceptibles de succomber à la mort due à des causes de maladies cardiovasculaires que les non-porteurs. Bien que la présence combinée des deux types d'hématopoïèse clonale n'était pas associée à un effet additif sur les critères d'évaluation liés aux maladies cardiovasculaires, elle a conféré un risque plus élevé de mortalité globale par rapport à ceux ayant un seul type d'hématopoïèse clonale. D'autres contributions scientifiques apportées au cours de mes études doctorales mettent l'accent sur le potentiel de l'utilisation de thérapies anti-inflammatoires pour réguler l'inflammation, et donc modifier le développement de l'hématopoïèse clonale, réduisant efficacement les événements cardiovasculaires et éventuellement les effets liés au cancer. Dans l'ensemble, les résultats de la thèse actuelle confirment que les processus inflammatoires sous-tendent le développement et la progression des maladies cardiovasculaires et du cancer. Cependant, les résultats de cette thèse soulignent la nécessité d'une évaluation continue, compte tenu des variations dans les liens entre l'inflammation, le cancer et les maladies cardiovasculaires à travers diverses voies inflammatoires et types de cancers. / Cancer and cardiovascular diseases are two major health threats to humanity. Survivors of cancer have a higher risk of developing and dying from cardiovascular disease compared to the general population. Similarly, patients with cardiovascular disease are also more likely to be diagnosed with cancer. While both conditions share many risk factors, cancer and cardiovascular disease have traditionally been studied in isolation. Recently, ongoing research has revealed biological commonalities between the two diseases. These findings are owed to significant scientific advances that have allowed for an expanded molecular characterization of inflammatory modulators, the elucidation of the structures of proteasome and inflammasome, and the advancement of knowledge in cellular immunity. Thanks to these advancements, valuable insights can now be gained into the complex circuity of the innate and adaptive immune response, as well as the mechanisms of the host defenses. The remarkable progress made in these areas has laid a strong foundation for inflammation biology, and the application of the principles learned in this field to human disease has only recently begun to yield fruitful results, leading to the exponential growth of the field of inflammation in cancer and cardiovascular disease. For both cancer and cardiovascular disease, immuno-modulation has recently emerged as a key factor in their treatment and management. Moreover, it has become apparent that targeting a particular inflammatory pathway to treat one condition can have significant implications for the other, reflecting the complex interplay between these two disease processes. These developments have enabled the recognition that inflammation is an active participant in the pathophysiological development and progression of both cancer and cardiovascular disease. However, our understanding of the role of inflammation in cancer and cardiovascular disease is still evolving, as ongoing research is necessary to uncover new insights into the complex mechanisms of their triangular relationship. In the present PhD thesis, we sought to conduct distinct analyses that would further our understanding and contribute to the current efforts in innovative research that could help reduce the growing burden of cancer and cardiovascular disease. First, we performed a genetic meta-analysis on the risk of incident cancer in patients with coronary artery disease taking statins. In that study, we were able to identify and replicate a genetic variant that was associated with a higher risk of incident cancer diagnosis in women statin users. The genetic variant was located in the human leukocyte antigen region that is largely responsible for the activation of T cells and the regulation of immune responses. These findings underscore the active involvement of inflammatory processes in the development of coronary artery disease and cancer. Second, we sought to explore the effect of clonal hematopoiesis, a condition in which certain blood cells are produced from a single mutated cell rather than from normal blood cell production processes, on the risk of death from cardiovascular-related causes in a large prospective cohort of patients diagnosed with cancer. In a first analysis, our findings showed that carriers of mosaic chromosomal alterations, a distinct type of clonal hematopoiesis, had a higher risk of death from coronary artery disease than non-carriers. In a follow-up analysis, our findings showed that carriers of clonal hematopoiesis of indeterminate potential were more likely to succumb to death from cardiovascular disease causes than non-carriers, and while the combined presence of both types of clonal hematopoiesis was not associated with an additive effect on cardiovascular-related endpoints, it did confer a greater risk of overall mortality compared to those with either type of clonal hematopoiesis alone. Other scientific contributions made during the course of my doctoral studies emphasize on the potential use of anti-inflammatory therapeutics to alter the course of clonal evolution, for the purpose of reducing cardiovascular-related outcomes, and simultaneously cancer-related endpoints. Overall, the results of this thesis support the notion that inflammatory processes underlie both diseases’ development and progression. However, the results of this thesis also highlight the need for continuous evaluation, taking into account the variations in the connections among inflammation, cancer, and cardiovascular disease across various inflammatory pathways and types of cancers.

L'insuffisance rénale chronique (IRC) se caractérise par la diminution progressive et irréversible des fonctions renales. Elle s'accompagne d'une accumulation d'un ensemble de toxines responsable du syndrome urémique. Le syndrome urémique touche tous les organes, et de façon préoccupante le système cardiovasculaire. Il est associé à une dysfonction endothéliale, à la production d'un stress oxydant et d'une inflammation. L'objectif de cette thèse était d'identifier les mécanismes moléculaires responsables des complications du syndrome urémique. La première partie a tenté d'identifier des épissages alternatifs associés à l'IRC. Deux épissages alternatifs ont été identifiés. Cependant, le petit nombre d'épissages alternatifs trouvé au vue du nombre de gènes étudiés, nous permet de conclure que si l'IRC peut être responsable de l'apparition d'épissages alternatifs, ce phénomène n'est pas déterminant dans la régulation de l'expression des gènes responsable des complications de l'IRC. Dans la deuxième partie, nous avons montré par une étude clinique que le taux d'une toxine urémique, l'acide indole acétique (IAA), était associé à la mortalité et à la survenue d'événements cardio-vasculaires. In vitro, l'IAA induit un stress oxydant et un signal inflammatoire par l'induction de la cyclooxygénase 2 (COX-2). Une voie inflammatoire non génomique impliquant aryl hydrocarbon receptor (AhR), p38 MAPK et NF-κB est responsable de l'induction de la COX-2 endothéliale par l'IAA. Nos travaux ont identifié de nouvelles cibles thérapeutiques dont la modulation pourrait avoir un impact sur la mortalité cardiovasculaire des patients présentant une maladie rénale chronique. / Chronic kidney disease (CKD) is characterized by an irreversible decrease in kidney functions. Accumulation of uremic toxins is implicated in the uremic syndrome. Uremic syndrome affects all organs and particularly the cardiovascular system. The aim of this thesis was to identify and understand the molecular mechanisms implicated in the uremic syndrome.The first part attempted to ascertain the existence of alternative splice events associated with CKD. Two alternative splicing were identified. The small number of alternative splice events highlighted allows us to conclude that this phenomenon does not seem to be a key event in the modulation of gene expression during CKD.In the second part of this work, we demonstrated that the plasmatic concentration of an uremic toxin, Indole-3-acetic acid (IAA), is associated with all-cause mortality and major cardiovascular events. In vitro, we demonstrated that IAA induced endothelial cyclooxygenase-2 expression and endothelial oxidative stress production. IAA activated an endothelial Aryl hydrocarbon receptor/P38MAPK/NF-κB pathway. The activation of this inflammatory AHR dependant pathway could play a critical role in the increase of cardiovascular morbidity and mortality observed during CKD.Our work provides new therapeutic targets. The modulation of their activation could reduce cardiovascular mortality in patients with chronic kidney disease.

O prognóstico após a parada cárdio-respiratória (PCR) e reanimação cardio-pulmonar (RCP) depende de intervenções críticas, particularmente, do tempo de resposta entre a chamada de socorro ou resgate, até a chegada ao local onde se encontra a vítima, além das compressões torácicas eficazes, da desfibrilação precoce e do suporte avançado de vida. Para avaliar a eficácia e a adequação dos procedimentos de RCP durante a PCR, entidades e associações científicas se reuniram e elaboraram o Utstein Style out-of-hospital, cujas definições e instrumento, usados para registro do evento, têm sido amplamente utilizadas em todo o mundo, bem como para estudos publicados sobre atendimento à parada cardíaca. A adoção de um instrumento de consenso internacional levou a uma grande evolução guidelines de reanimação e a progressos científicos, possibilitando a troca de informações mais efetivas para promover comparações internacionais em relação aos procedimentos de ressuscitação tendo como propósito codificar variáveis, mensurar aspectos do processo e avaliar resultados dos atendimentos na PCR fora do hospital. Apesar do grande numero de PCR que ocorre no Brasil, não há, até então, um instrumento em nosso idioma adaptado à nossa realidade. Este trabalho teve pro objetivos realizar a tradução e adaptação cultural do Utstein Style out-of-hospital, com base nos pressupostos metodológicos de Guillemin (2002). O instrumento foi, também, testado em dois centros de atendimento pré-hospitalar para verificar a viabilidade de sua utilização. Como resultado deste estudo metodológico obtivemos um instrumento traduzido para o idioma português, com algumas modificações necessárias para sua adaptação à cultura nacional, sugeridas por um comitê de juizes e cuja aplicação, ainda que em pré-teste, permitiu verificar que os resultados obtidos assemelham-se aos dados internacionais. O maior número de causas de PCR ocorreu em adultos do sexo feminino (58,8%), com idade acima de 29 anos. Grande parte das paradas cardíacas foi identificada por espectador (47,0%), pelo Serviço Médico de Emergência (35,5) e pelo médico (17,5%). Quanto à ocorrência da PCR, 82,4% foi por causa desconhecida e 17,6% por trauma / The prognostic after the cardiac arrest and cardio-pulmonary resuscitation (CPR) is dependent of critical interventions, particularly, time reply called until place, efficient chest compressions early defibrillation and the advanced life support. The definitions of the Utstein style and the instrument of register have been widely used in published studies of cardiopulmonary arrest (CPA), what it took to a great evolution and the progress for international consensuses on science and guidelines of resuscitation, making possible the exchange of information more effective to promote international auditorship in relation to the resuscitation procedures having as intention to codify variable, to measure aspects of the process and to evaluate resulted of the take care of in the CPA of the hospital. Currently several countries already use with this purpose. The Utstein was approved by the international committees. Although the great one number of CPA in Brazil, we did not possess an instrument in our language and adapted. This instrument underwent a process of translation into Portuguese, back-translation into its original language and finally analysis by a committee of judges to evaluate semantics, idiomatic, cultural and conceptual equivalences, with the authorization of the AHA, following the recommendations of Guillemin, revised in 2002. The instrument was tested in two centers the out-of-hospital attendance to verify the use of in the Brazilian country and making possible comparisons with international data, enriching adding the evolution of the CPR in the world. As result of this study we got an instrument translated into the Portuguese language, with some necessary modifications for its adaptation to the national culture, suggested for a committee of judges and whose application allowed verifying that the gotten results resemble it the international data. The biggest number of CPA causes occurred in adults, females (58.8%), with age above of 29 years. Great part of the CPA was identified by witness (47.0%), the Emergency Medical Service (35.5%) and by the physician (17.5%). Several occurrences of CPA, 82.4% it was for unknown cause and 17.6% for trauma

De nos jours, les mesures sans contact du signal cardiaque du patient en utilisant le radar Doppler a suscité un intérêt considérable chez les chercheurs, surtout que les électrocardiographes traditionnels avec des électrodes fixes ne sont pas pratiques dans certains cas comme les nourrissons ou les victimes de brûlure. En raison de la sensibilité des micro­ondes à de petits mouvements, le radar a été utilisé comme système de surveillance de l'activité cardio-pulmonaire humaine. Selon l'effet Doppler, un signal de fréquence constante est transmis vers la cible ayant un déplacement variable puis réfléchi. Le signal réfléchit possède une variation de phase par rapport au temps. Dans notre cas, la cible est la poitrine du patient; Le signal réfléchi de la poitrine de la personne contient le signal cardiorespiratoire. Le système est basé sur un analyseur de réseau vectoriel et deux antennes cornet. Le S21 est calculé en utilisant un analyseur de réseau. La variation de phase de S21 contient des informations de l'activité cardio-pulmonaire. Des techniques de traitement sont utilisées pour extraire le signal cardiaque de la variation de la phase de S21 . Cette thèse présente une étude comparative dans la détection des signaux de battements cardiaques au niveau de la puissance rayonnée et de la fréquence opérationnelle. Les puissances rayonnées sont comprises entre 3 et -17 dBm et les fréquences opérationnelles utilisées sont 2.4, 5.8, 1 0 et 20 GHz. Cela permet de spécifier la fréquence opérationnelle optimale, qui donne un compromis entre la puissance minimale émise ainsi que la complexité du système de mesure. De plus, une étude comparative entre plusieurs méthodes de traitement de signal est proposée pour extraire la meilleure méthode qui permet de mesurer le signal cardiaque et par suite extraire ses paramètres. Des techniques de traitement basées sur des transformées en ondelettes ou le filtrage classique sont présentées et utilisées afin de faire une comparaison entre elles. Le paramètre extrait dans cette thèse est le taux des battements cardiaques. Les mesures ont été effectuées simultanément avec un électrocardiographe afin de valider les mesures du signal cardiaque. Puisque la personne peut se déplacer d'une pièce à une autre à l'intérieur de son domicile, des mesures des quatre côtés de la personne et derrière un mur sont réalisées. Ajoutons une approche de modélisation fondée sur la mesure cardio-respiratoire pour une personne qui exerce une marche en avant. De plus, une comparaison entre un système à micro-ondes à simple et deux antennes pour une personne qui prend son souffle est effectuée afin de tester la précision du système à antenne unique par rapport au a la deuxième. Par suite, des mesures sont effectuées pour une personne qui respire en utilisant un système à une seule antenne. / Nowadays, contact-less monitoring patient's heartbeat using Doppler radar has attracted considerable interest of researchers, especially when the traditional electrocardiogram (ECG) measurements with fixed electrodes is not practical in some cases like infants at risk or sudden infant syndrome or burn victims. Due to the microwave sensitivity toward tiny movements, radar has been employed as a noninvasive monitoring system of human cardiopulmonary activity. According to Doppler effect, a constant frequency signal reflected off an object having a varying displacement will result in a reflected signal, but with a time varying phase. In our case, the object is the patient's chest; the reflected signal of the person's chest contains information about the heartbeat and respiration. The system is based on a vector network analyzer and 2 horn antennas. The S21 is computed using a vector network analyzer. The phase variation of S21 contains information about cardiopulmonary activity. Processing techniques are used to extract the heartbeat signal from the S21 phase. This thesis presents a comparative study in heartbeat detection, considering different radiated powers and frequencies. The radiated powers used are between 3 and -17 dBm and the operational frequencies used are 2.4, 5.8, 10 and 20 GHz. This helps to make a compromise between the minimum power emitted and the complexity of the measurement system. In addition, a comparative study of several signal processing methods is proposed to extract the best technique for heartbeat measurement and thus to extract its parameters. Processing techniques are based on wavelet transforms and conventional filtering in order to make a comparison between them. The parameter extracted in this thesis is the heartbeat rate HR. Measurements were performed simultaneously with a PC-based electrocardiograph to validate the heartbeat rate measurement. Since the person can move from a room to another inside his home, measurements from the four sides of the person and behind a wall are performed. In addition, a modeling approach based on cardio-respiratory measurement for a person who is walking forward is presented. Furthermore, a comparison between single and two-antenna microwave systems for a non-breathing person is carried out to test the accuracy of the single-antenna system relative to the two ­antenna microwave system. After that, measurements are performed using one antenna microwave system for a person who breathes normally.

Les néoplasies myéloprolifératives (NMP) sont des hémopathies myéloïdes clonales, chroniques et prolifératives. Les plus fréquentes sont la polyglobulie de Vaquez et la thrombocytémie essentielle. Elles s’accompagnent de risques importants de thrombose (artérielles et veineuses) et de transformation en pathologies plus agressives (myélofibrose secondaire et leucémie aigüe). Les thromboses peuvent être la situation diagnostique de ces maladies, ou survenir au cours de la prise en charge. Le sujet de cette thèse est d’étudier la relation clinique entre NMP et thrombose. Dans un contexte de survenue de thrombose veineuse idiopathique, sans antécédent NMP, nous nous sommes intéressés à la recherche de mutation clonale chez les patients comme moyen diagnostique d’une NMP. Nous avons ainsi exploité la cohorte EDITH du CIC en prenant les patients ayant expérimentés un puis une récurrence thrombotique. A l’inverse, nous avons constitué une base de données (OBENE) des patients pris en charge pour une NMP au CHRU de Brest.Nous avons ensuite exploité cette base, en analysant la fréquence et l’impact des arythmies cardiaques auriculaires, la balance bénéfice-risque à l’utilisation des NACO, l’impact des statines sur la réduction du risque de thrombose ainsi que la fréquence et l’impact de la nonadhérence aux traitements dans les PV et TE.NMP et thromboses sont liées, il est donc nécessaire d’approfondir les connaissances de leur physiopathologie spécifique pour améliorer la prévention et le traitement des épisodes. Cette thèse amène quelques réponses àcertaines questions mais elle est surtout le point de départ de réflexion commune entre les praticiens et biologistes intéressés par ces domaines. / The myeloproliferative neoplasms (MPN) are clonal myeloid, chronic and proliferative disorders. The most frequent are polycythemia vera and essential thrombocythemia. The more frequent complications are thromboses (arterial and venous) and phenotypic evolutions (secondary myelofibrosis and acute leukemia). Thromboses can be a situation of diagnosis or observed during the followup of a MPN. This thesis is focused on the clinical link between MPN and thromboses.In a context of idiopathic venous thromboses (first event or recurrence), without medical history of MPN, we have tested patients for the most frequent MPN clonal mutations. So, we have used the informations and patients of the dedicated EDITH cohort.On the other hand, we have constituted a MPN database (OBENE) of the patients diagnosed for MPN in our Hospitalcentre. By this way, we have analysed the frequency and impact of atrial arrhythmias, the benefit-risk balance of the use of DOAC, the impact of statins to reduce the thrombotic risk and the frequency and impact of the treatment nonadherence in this population.MPN and thromboses are linked, so it is necessary to increase our knowledge of their physiopathology to improve prevention and treatment of the events. This thesis brings some answers to some questions but, she is almost the starting point of common reflexion between clinicians and biologists interested in these domains.

O prognóstico após a parada cárdio-respiratória (PCR) e reanimação cardio-pulmonar (RCP) depende de intervenções críticas, particularmente, do tempo de resposta entre a chamada de socorro ou resgate, até a chegada ao local onde se encontra a vítima, além das compressões torácicas eficazes, da desfibrilação precoce e do suporte avançado de vida. Para avaliar a eficácia e a adequação dos procedimentos de RCP durante a PCR, entidades e associações científicas se reuniram e elaboraram o Utstein Style out-of-hospital, cujas definições e instrumento, usados para registro do evento, têm sido amplamente utilizadas em todo o mundo, bem como para estudos publicados sobre atendimento à parada cardíaca. A adoção de um instrumento de consenso internacional levou a uma grande evolução guidelines de reanimação e a progressos científicos, possibilitando a troca de informações mais efetivas para promover comparações internacionais em relação aos procedimentos de ressuscitação tendo como propósito codificar variáveis, mensurar aspectos do processo e avaliar resultados dos atendimentos na PCR fora do hospital. Apesar do grande numero de PCR que ocorre no Brasil, não há, até então, um instrumento em nosso idioma adaptado à nossa realidade. Este trabalho teve pro objetivos realizar a tradução e adaptação cultural do Utstein Style out-of-hospital, com base nos pressupostos metodológicos de Guillemin (2002). O instrumento foi, também, testado em dois centros de atendimento pré-hospitalar para verificar a viabilidade de sua utilização. Como resultado deste estudo metodológico obtivemos um instrumento traduzido para o idioma português, com algumas modificações necessárias para sua adaptação à cultura nacional, sugeridas por um comitê de juizes e cuja aplicação, ainda que em pré-teste, permitiu verificar que os resultados obtidos assemelham-se aos dados internacionais. O maior número de causas de PCR ocorreu em adultos do sexo feminino (58,8%), com idade acima de 29 anos. Grande parte das paradas cardíacas foi identificada por espectador (47,0%), pelo Serviço Médico de Emergência (35,5) e pelo médico (17,5%). Quanto à ocorrência da PCR, 82,4% foi por causa desconhecida e 17,6% por trauma / The prognostic after the cardiac arrest and cardio-pulmonary resuscitation (CPR) is dependent of critical interventions, particularly, time reply called until place, efficient chest compressions early defibrillation and the advanced life support. The definitions of the Utstein style and the instrument of register have been widely used in published studies of cardiopulmonary arrest (CPA), what it took to a great evolution and the progress for international consensuses on science and guidelines of resuscitation, making possible the exchange of information more effective to promote international auditorship in relation to the resuscitation procedures having as intention to codify variable, to measure aspects of the process and to evaluate resulted of the take care of in the CPA of the hospital. Currently several countries already use with this purpose. The Utstein was approved by the international committees. Although the great one number of CPA in Brazil, we did not possess an instrument in our language and adapted. This instrument underwent a process of translation into Portuguese, back-translation into its original language and finally analysis by a committee of judges to evaluate semantics, idiomatic, cultural and conceptual equivalences, with the authorization of the AHA, following the recommendations of Guillemin, revised in 2002. The instrument was tested in two centers the out-of-hospital attendance to verify the use of in the Brazilian country and making possible comparisons with international data, enriching adding the evolution of the CPR in the world. As result of this study we got an instrument translated into the Portuguese language, with some necessary modifications for its adaptation to the national culture, suggested for a committee of judges and whose application allowed verifying that the gotten results resemble it the international data. The biggest number of CPA causes occurred in adults, females (58.8%), with age above of 29 years. Great part of the CPA was identified by witness (47.0%), the Emergency Medical Service (35.5%) and by the physician (17.5%). Several occurrences of CPA, 82.4% it was for unknown cause and 17.6% for trauma