A detailed assessment of adverse perioperative outcomes of the elderly treated with radical cystectomy for bladder cancer

Objectifs: Les données provenant des centres de soins tertiaires suggèrent que le taux de mortalité péri-opératoire (MPO) après cystectomie notés pour les patients âgés (septuagénaires et octogénaires) n’excède pas celle des patients plus jeunes. Toutefois, les données provenant de la communauté démontrent un phénomène inverse. Spécifiquement, la MPO est plus élevés chez les ainés. Dans cette thèse nous allons présenter une réévaluation contemporaine du taux de MPO après cystectomie. Méthodes: Entre 1988 et 2006, 12722 cystectomies radicales pour le carcinome urothéliale de la vessie ont été enregistrées dans la banque de données SEER. Le taux de MPO a été évalué dans les analyses de régression logistique univariées et multivariées à 90 jours après cystectomie radicale. Les covariables incluaient: le sexe, l’ethnie, l’année de chirurgie, la région d’origine du patient ainsi que le grade et le stade de la tumeur. Résultats: Parmi tous les patients, 4480 étaient des septuagénaires (35.2%) et 1439 étaient des octogénaires (11.3%). Le taux de MPO à 90 jours était de 4% pour la cohorte entière vs. 2% pour les patients moins de 69 ans vs. 5.4% pour les septuagénaires vs. 9.2% pour les octogénaires. Dans les analyses de régression logistiques multivariées, les septuagénaires (OR=2.80; <0.001) et les octogénaires (OR=5.02; <0.001) avaient reçu un taux de MPO plus augmenté que les patients moins de 70 ans après une cystectomie radicale. Conclusion: Cette analyse épidémiologique basée sur les donnés le plus contemporaines démontre que l’âge avancée représente un facteur de risque pour un taux de MPO plus élevé.

Corps et âme en mouvement. Expression et signification du mouvement dans la peinture de vases en Grèce ancienne (VIe-IVe s. av. J.-C.). Ivresse, possession divine et mort.

Thèse réalisée en cotutelle avec l'université de Franche-Comté, école doctorale Langage, espace, temps et société.

A Data Mining Approach for the Identification of Adverse Drug Events (ADE) resulting from Drug-Drug Interactions (DDI) to improve pharmacovigilance

In the current study, epidemiology study is done by means of literature survey in groups identified to be at higher potential for DDIs as well as in other cases to explore patterns of DDIs and the factors affecting them. The structure of the FDA Adverse Event Reporting System (FAERS) database is studied and analyzed in detail to identify issues and challenges in data mining the drug-drug interactions. The necessary pre-processing algorithms are developed based on the analysis and the Apriori algorithm is modified to suit the process. Finally, the modules are integrated into a tool to identify DDIs. The results are compared using standard drug interaction database for validation. 31% of the associations obtained were identified to be new and the match with existing interactions was 69%. This match clearly indicates the validity of the methodology and its applicability to similar databases. Formulation of the results using the generic names expanded the relevance of the results to a global scale. The global applicability helps the health care professionals worldwide to observe caution during various stages of drug administration thus considerably enhancing pharmacovigilance

Possession and Immoveable Property: The History of Two Connected Concepts

Possession and property are two different sides of the same coin. The two institutions have the same axis: the benefit, mainly economic, of a good. In countries like Colombia and Peru, important reforms have been introduced whose main effect has been the following one: the approach to these two institutions. In this article we will speak of these two institutions, today more than ever, connected.

Sequential genome-wide association studies for monitoring adverse events in the clinical evaluation of new drugs

Pharmacovigilance, the monitoring of adverse events (AEs), is an integral part in the clinical evaluation of a new drug. Until recently, attempts to relate the incidence of AEs to putative causes have been restricted to the evaluation of simple demographic and environmental factors. The advent of large-scale genotyping, however, provides an opportunity to look for associations between AEs and genetic markers, such as single nucleotides polymorphisms (SNPs). It is envisaged that a very large number of SNPs, possibly over 500 000, will be used in pharmacovigilance in an attempt to identify any genetic difference between patients who have experienced an AE and those who have not. We propose a sequential genome-wide association test for analysing AEs as they arise, allowing evidence-based decision-making at the earliest opportunity. This gives us the capability of quickly establishing whether there is a group of patients at high-risk of an AE based upon their DNA. Our method provides a valid test which takes account of linkage disequilibrium and allows for the sequential nature of the procedure. The method is more powerful than using a correction, such as idák, that assumes that the tests are independent. Copyright © 2006 John Wiley & Sons, Ltd.

Action following the discovery of a global association between the whole genome and adverse event risk in a clinical drug-development programme

Observation of adverse drug reactions during drug development can cause closure of the whole programme. However, if association between the genotype and the risk of an adverse event is discovered, then it might suffice to exclude patients of certain genotypes from future recruitment. Various sequential and non-sequential procedures are available to identify an association between the whole genome, or at least a portion of it, and the incidence of adverse events. In this paper we start with a suspected association between the genotype and the risk of an adverse event and suppose that the genetic subgroups with elevated risk can be identified. Our focus is determination of whether the patients identified as being at risk should be excluded from further studies of the drug. We propose using a utility function to? determine the appropriate action, taking into account the relative costs of suffering an adverse reaction and of failing to alleviate the patient's disease. Two illustrative examples are presented, one comparing patients who suffer from an adverse event with contemporary patients who do not, and the other making use of a reference control group. We also illustrate two classification methods, LASSO and CART, for identifying patients at risk, but we stress that any appropriate classification method could be used in conjunction with the proposed utility function. Our emphasis is on determining the action to take rather than on providing definitive evidence of an association. Copyright (C) 2008 John Wiley & Sons, Ltd.

Adverse gastrointestinal effects of arginine and related amino acids

Oral supplements of arginine and citrulline increase local nitric oxide (NO production in the small intestine and this may be harmful under certain circumstances. Gastrointestinal toxicity was therefore reviewed with respect to the intestinal physiology of arginine, citrulline, ornithine, and cystine (which shares the same transporter) and the many clinical trials of supplements of the dibasic amino acids or N-acetylcysteine (NAC. The human intestinal dibasic amino acid transport system has high affinity and low capacity. L-Arginine (but not lysine, ornithine, or D-arginine) induces water and electrolyte secretion that is mediated by NO, which acts as an absorbagogue at low levels and as a secretagogue at high levels. The action of many laxatives is NO mediated and there are reports of diarrhea following oral administration of arginine or ornithine ihine. The clinical data cover a wide span of arginine intakes f rom 3 g/d to > 100 g/d, but the standard of reporting adverse effects (e.g. nausea, vomiting, and diarrhea) was variable. Single doses of 3-6 g rarely provoked side effects and healthy athletes appeared to be more susceptible than diabetic patients to gastrointestinal symptoms at individual doses >9 g. This may relate to an effect of disease on gastrointestinal motility and pharmacokinetics. Most side effects of arginine and NAC occurred at single doses of >9 g in adults >140 mg/kg) often when part of a daily regime of similar to>30 g/d (>174 mmol/d). In the case of arginine, this compares with the laxative threshold of the nonabsorbed disaccharide alcohol, lactitol (74 g or 194 mmol). Adverse effects seemed dependent on the dosage regime and disappeared if divided doses were ingested (unlike lactitol). Large single doses of poorly absorbed amino acids seem to provoke diarrhea. More research is needed to refine dosage strategies that reduce this phenomenon. It is suggested that dipeptide forms of arginine may meet this criterion.

Surveillance for adverse events after DTwP/Hib vaccination in Brazil: Sensitivity and factors associated with reporting

We estimated the sensitivity, i.e., the proportion of all cases of adverse events following immunization (AEFIs) reported to the Brazilian passive surveillance for adverse events following immunization (PSAEFI) with the diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae type b (DTwP/Hib) vaccine, as well as investigating factors associated with AEFIs reporting. During 2003-2004, 8303 AEFIs associated with DTwP-Hib were reported; hypotonic-hyporesponsive episodes (HHEs), fever and convulsions being the most common. Cure without sequel was achieved in 98.4% of the cases. The mean sensitivity of the PSAEFI was 22.3% and 31.6%, respectively, for HHE and convulsions, varying widely among states. Reporting rates correlated positively with the Human Development Index and coverage of adequate prenatal care, correlating negatively with infant mortality rates. Quality of life indicators and the degree of organization of health services are associated with greater PSAEFI sensitivity. In addition to consistently describing the principal AEFIs, PSAEFI showed the DTwP/Hib vaccine to be safe and allayed public fears related to its use. (C) 2010 Elsevier Ltd. All rights reserved.

Assets, markets and poverty in Brazil

Esse artigo estabelece uma base para pesquisas que tratam da relação entre pobreza, distribuição de recursos e operação do mercado de capitais no Brasil. O principal objetivo é auxiliar a implementação de políticas de reforço de capital dos pobres. A disponibilidade de novas fontes de dados abriu condições inéditas para implementar uma análise de posse de ativos e pobreza nas áreas metropolitanas brasileiras. A avaliação de distribuição de recursos foi estruturada sobre três itens: Capital físico, capital humano e capital social. A estratégia empírica seguida é de analisar três diferentes tipos de impactos que o aumento dos ativos dos pobres podem exercer no nível de bem estar social. A primeira parte do artigo avalia a posse de diferentes tipos de capitais através da distribuição de renda. Esse exercício pode ser encarado como uma ampliação de medidas de pobreza baseadas em renda pela incorporação de efeitos diretos exercidos pela posse de ativos no bem estar social. A segunda parte do artigo descreve o impacto de geração de renda que a posse de ativos pode ter sobre os pobres. Estudamos como a acumulação de diferentes tipos de capital impactam os índices de pobreza baseados na renda usando regressões logísticas. A terceira parte estuda o efeito que o aumento da posse de ativos dos pobres tem no melhoramento da habilidade dos indivíduos pobres em lidar com choques adversos da renda. Estudamos a interação entre a dinâmica da renda, imperfeições do mercado de capitais e comportamentos financeiros levando em consideração diferentes horizontes de tempo. As questões de longo prazo estão relacionadas com o estudo das flutuações de renda de baixa freqüência e ciclo da vida da posse de ativos usando análise de coorte. As questões de curto prazo estão relacionadas com o comportamento do pobre e as perdas de bem estar ao lidar com hiatos de alta freqüência entre renda e consumo desejado. A análise da dinâmica de renda e pobreza é conduzida a partir da combinação de dados de painel de renda com dados qualitativos sobre comportamento financeiro de curto prazo das famílias.

Signaling in dynamic markets with adverse selection

Nesta dissertação, consideram-se trocas em mercados descentralizados com seleção adversa. Diferentemente da literatura até o momento, supomos que vendedores informados (e não compradores desinformados) fazem ofertas take-it-or-leave-it, de forma que sinalização através de preços é possível. Estabelecemos uma caracterização parcial do conjunto de equilíbrio, encontramos condições necessárias e suficientes para a existência de um equilíbrio e mostramos que todo equilíbrio apresenta sinalização se o problema de seleção adversa for suficientemente severo. Além disso, provamos o resultado surpreendente que o maior bem-estar atingido em equilíbrio é invariante às fricções do mercado. Também apresentamos condições necessárias e suficientes para a existência de equilíbrios separantes, que caracterizamos completamente. Mostramos que o conjunto de payoffs associados a equilíbrios separantes é invariante às fricções. Concluímos com uma caracterização completa do conjunto de equilíbrio com apenas dois tipos, e comparamos nossos resultados com os de Moreno e Wooders (2010), que analisam o caso em que compradores têm todo o poder de mercado. Nossos resultados mostram que sinalização através dos preços tem um impacto não trivial tanto nos resultados do mercado quanto no bem-estar.

Adverse selection with endogenous entry

Usando como base o ambiente descrito em Moreno e Wooders (2010), neste trabalho, analisamos trocas em um ambiente dinâmico, descentralizado e com seleção adversa. Ao contrário dos autores e da literatura, não consideramos a proporção de ativos de alta qualidade entrantes como independente das características do mercado. Desse modo, adaptamos o modelo dinâmico básico de seleção adversa para incorporar a decisão do vendedor sobre a possibilidade de pagar ou não um preço e transformar seu ativo de baixa qualidade em um ativo de alta qualidade antes de entrar no mercado. E, sob essas condições, mostramos que o bem-estar pode se comportar de maneira diferente do modelo tradicional.