Problématique : Plusieurs expositions résidentielles ont été associées à la prévalence de l’asthme. Toutefois, peu d’études populationnelles ont examiné la relation entre ces facteurs et un asthme mal maîtrisé chez l’enfant. Objectif : Évaluer les facteurs environnementaux résidentiels associés à un asthme mal maîtrisé chez les enfants montréalais âgés de 6 mois à 12 ans. Méthodes : Les données sont tirées d’une enquête transversale menée en 2006 sur la santé respiratoire d’enfants montréalais âgés de 6 mois à 12 ans (n=7980). La maîtrise de l’asthme a été évaluée chez les enfants avec un asthme actif au cours de l’année précédent l’enquête (n=980) selon des critères recommandés par les lignes directrices canadiennes sur l’asthme. Les rapports de prévalence (RP) et les intervalles de confiance (IC) à 95 % caractérisant l’association entre les facteurs environnementaux, incluant la présence d’allergènes, d’irritants, d’humidité et de moisissures, et le risque d’un asthme mal maîtrisé ont été estimés à l’aide de modèles de régression log-binomiale. Les sujets avec une maîtrise acceptable de l’asthme ont été comparés à ceux dont la maladie était mal maîtrisée. Résultats : Des 980 enfants avec un asthme actif au cours de l’année précédant l’enquête, 36 % ont rencontré au moins un des critères des lignes directrices canadiennes suggérant un asthme mal maîtrisé. Les caractéristiques de la population associées à un asthme mal maîtrisé sont : un plus jeune âge, des antécédents d’atopie parentale, une faible scolarisation de la mère, une mère d’origine étrangère et le statut de locataire. Après ajustement pour l’âge de l’enfant, l’atopie parentale et l’exposition à la fumée de tabac au domicile, une intensité de trafic élevée à proximité du domicile (RP, 1,35; IC 95 %, 1,00-1,81) et la localisation au sous-sol de la chambre de l’enfant ou de sa résidence (RP 1,30; IC 95 %, 1,01-1,66) étaient associées à un risque accru d’asthme mal maîtrisé. Conclusions : Une maîtrise sous-optimale de l’asthme semble être associée à l’exposition au trafic routier et à des conditions d’humidité excessive et probablement de moisissures. Cette dernière exposition étant plus fréquente, elle a probablement un plus grand impact en matière de santé publique. / Background: Home environmental exposures may impede asthma control in children. However, few population-based studies have investigated this relationship. Objective: Identify environmental home exposures associated with poor asthma control among asthmatic children less than 12 years of age in Montreal. Methods: This cross-sectional population-based study used data from a respiratory health survey of Montreal children aged 6 months to 12 years conducted in 2006 (n=7,980). Asthma control was assessed among those with active asthma in the year prior to the survey (n=980) using an adaptation of the Canadian asthma consensus report clinical parameters. Using log-binomial regression models, prevalence ratios (PR) with 95 % confidence intervals (CI) were estimated to explore the relationship between inadequate control of asthma and environmental home exposures, including allergens, irritants, mold and dampness indicators. Subjects with acceptable asthma control were compared with those with inadequate disease control. Results: Of 980 children with active asthma in the year prior to the survey, 36 % met at least one of the five criteria outlined in the Canadian asthma guidelines as to poor control of their disease. The population’s characteristics found to be related with a lack of asthma control were: younger age, a history of parental atopy, low maternal education level, foreign-born mothers and tenant occupancy. After adjustments for the child’s age, parental atopy and tobacco smoke exposure at home, children living along high-traffic density streets (PR, 1.35; 95 % CI, 1.00-1.81) and those with their bedroom or residence in the basement (PR, 1.30; 95 % CI, 1.01-1.66) were found to be at increased risk of poor asthma control. Conclusions: Suboptimal asthma control appears to be mostly associated with traffic, along with mold and moisture conditions, the latter being a more frequent exposure and therefore having a greater public health impact.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal.

Le pneumothorax spontané (PS) est une pathologie le plus souvent bégnine quand elle survient chez un sujet sain. Le principal risque est la récidive dans environ 30 % des cas. L'évolution des connaissances concernant sa physiopathologie, associée aux résultats des études cliniques évaluant sa prise en charge en ambulatoire, font reconsidérer les stratégies de traitement initial et de prévention des récidives. Nos travaux de recherche sur le PS ont plusieurs axes relatifs aux aspects épidémiologiques, diagnostiques et thérapeutiques de sa prise en charge initiale, en particulier dans les services d'urgence. Cette thèse s'articule autour de 3 volets. Le premier volet correspond à l'identification de facteurs associés à la récurrence du PS. Si le tabac, le sexe ou l'intoxication au cannabis sont des facteurs de risque reconnu d'occurence, leur impact sur la récidive n'est pas consensuel. C'est pourquoi nous avons mené une étude rétrospective multicentrique dans des services d'urgence français. Sur cette série de 1491 PSP, dont respectivement 62 et 38% correspondaient à un premier épisode et à une récidive, aucun facteur de risque clinique n'était lié à la récidive. Malgré des limites méthodologiques liées notamment à son caractère rétrospectif, cette série représente la plus importante quantitativement jamais publiée. Un deuxième axe concerne l'étude de la prise en charge thérapeutique initiale du PS aux urgences. Bien que des études préliminaires aient montré des taux de succès de plus de 70% en cas de prise en charge ambulatoire, en l'absence de consensus au niveau international ni de recommandations françaises, le choix du traitement initial revient au praticien prenant en charge le patient. Très peu de données existent sur cette prise en charge initiale dans la vraie vie, qu'il s'agisse de la décision thérapeutique, du matériel employé ou du spécialiste impliqué. Ainsi, nous avons mené une étude rétrospective à propos de 1849 PS pris en charge dans 14 services d'urgence en France afin de documenter la filière de prise en charge. Cette étude a montré que la prise en charge était pluridisciplinaire, que l'abstention était la stratégie thérapeutique de première intention pour la moitié des patients. et qu'en cas de geste le drainage était choisi dans près de 80% des cas. La stratégie ambulatoire ne concernait que 239 patients, dont 230 PS primitifs et 9 PS secondaires (4%), très majoritairement en cas d'abstention thérapeutique. Le troisième volet concerne l'évaluation médico-économique de deux stratégies de traitement d'un premier PS primitif: drainage thoracique standard versus une stratégie combinée avec exsufflation en première intention (étude EXPRED). L'étude a porté sur une série de 379 patients, randomisés en deux bras. Les résultats de cette étude multicentrique ont montré que les deux stratégies étaient équivalentes en ce qui concerne le succès immédiat, évalué sur le recollement pleural, et le taux de récidive à un an. L'évaluation médico économique, conduite avec une approche de minimisation des coûts et avec l'hypothèse d'une équivalence des deux stratégies, dans la perspective du payeur, a montré que l'exsufflation était une stratégie plus coût efficace que le drainage. Au final, les résultats de ces travaux montrent qu'en pratique, actuellement, dans les services d'urgences en France, l'abstention thérapeutique et le drainage thoracique sont préférentiellement choisis lors de la prise en charge du PS, à l'inverse des stratégies ambulatoires. Les connaissances apportées par l'étude EXPRED et celles sur les facteurs de risque de récidive sont de nature à influencer les recommandations françaises à venir. De futurs travaux de recherche devront s'attacher à identifier les freins à l'implantation de ces recommandations, ainsi que ceux relatifs à l'adhésion à une stratégie ambulatoire de prise en charge / Spontaneous pneumothorax (SP) is usually a benign pathology, when it occurs at a healthy subject. Recurrence is the main risk, in approximately 30% of the cases. Current knowledge concerning physiopathology, associated with the results of clinical trials estimating ambulatory treatment, make reconsider the strategies of initial treatment and prevention of recurrence. Our research on SP have several topics related to epidemiological, diagnostic and therapeutic aspects of initial management in the Emergency Department (ED). This work treats three axis. The first axis corresponds to identification of factors associated with recurrence of primary spontaneous pneumothorax (PSP). If tobacco, gender or use of cannabis are identified as a risk factor of occurrence, their impact on recurrence are not consensual. Then, we conducted a retrospective multicenter study in 14 french ED. In this population of 1491 PSP, among whom respectively 62 and 38% corresponded to a first episod and to a recurrence, no clinical risk factor of recurrence was highl ighted. In spite of methodological limits, in particular in line with its retrospective design, this series represents the most larger never published. The second axis concerns the study of initial treatrnent of PS in 14 ED. Although preliminary studies showed rates of success of more than 70% in case of ambulatory management, in the absence of international consensus and French recommandations, the choice of initial treatment depends on physicians decision. Few data exist on this initial management in real life condition, concerning therapeutic action, material devices used, or speciality of physicians implied. Again, we conducted a second retrospective study with 1849 PS in 14 french ED in France to precise healthcare pathways. The study showed that the management was multidisciplinary, abstention was the frst therapeutic strategy for half of patients and in case of intervention, chest tube was chosen in about 80% of cases. Ambulatory strategy concerned only 239 patients (14%), among whom 230 PSP and 9 secondary PS, mostly in case of abstention. The third axis concerns medical economic evaluation of two treatments strategies of first primary PS : chest tube drainage versus aspiration as first therapeutic action (EXPRED study).The study concerned a serie of 379 patients, randomized in Iwo arms. The results of this multicenter study showed that both strategies are equivalent concerning immediat success estimated on pneumothorax resolution and the rate of recurrence at one year. The medicoeconomic evaluation as a minimization of the costs and with the hypothesis of an equivalence of both strategies with the prospect of the payer, showed that aspiration was a strategy more cost effective than chest tube. Finally, results of these works showed that actually in practice, abstention and chest tube drainage are preferentially chosen for the management of PS in ED in France, compare to ambulatory strategy. Results of EXPRED study and knowledge about risk factors of recurrence can influence future french recommandations. Future research are necessary to identify barriers to implementation of these recommandations, as well asthose relative to adhesion of ambulatory management.

Some previously described environmental associations for atopic eczema may be due to reverse causation. We explored the role of reverse causation by comparing individual- and school-level results for multiple atopic eczema risk factors. The International Study of Asthma and Allergies in Childhood (i.e, ISAAC) Phase Three surveyed children in schools (the sampling unit) regarding atopic eczema symptoms and potential risk factors. We assessed the effect of these risk factors on atopic eczema symptoms using mixed-effect logistic regression models, first with individual-level exposure data and second with school-level exposure prevalence. Overall, 546,348 children from 53 countries were included. At ages 6–7 years, the strongest individual-level associations were with current paracetamol use (odds ratio [OR] = 1.45, 95% confidence interval [CI] = 1.37–1.54), which persisted at school-level (OR = 1.55, 95% CI = 1.10–2.21), early-life antibiotics (OR = 1.41, 95% CI = 1.34–1.48), and early-life paracetamol use (OR = 1.28, 95% CI = 1.21–1.36), with the former persisting at the school level, whereas the latter was no longer observed (OR = 1.35, 95% CI = 1.00–1.82 and OR = 0.94, 95% CI = 0.69–1.28, respectively). At ages 13–14 years, the strongest associations at the individual level were with current paracetamol use (OR = 1.57, 95% CI = 1.51–1.63) and open-fire cooking (OR = 1.46, 95% CI = 1.33–1.62); both were stronger at the school level (OR = 2.57, 95% CI = 1.84–3.59 and OR = 2.38, 95% CI = 1.52–3.73, respectively). Association with exposure to heavy traffic (OR = 1.31, 95% CI = 1.27–1.36) also persisted at the school level (OR = 1.40, 95% CI = 1.07–1.82). Most individual- and school-level effects were consistent, tending to exclude reverse causation. / Revisión por pares

Ce travail de thèse a porté sur l’étiologie des leucémies aigües (LA) de l’enfant, et s’est concentré sur les questions (1) du risque de LA chez les enfants conçus par assistance médicale à la procréation (AMP) ; (2) du rôle protecteur d’une supplémentation maternelle en acide folique ; (3) du rôle protecteur de l’exposition précoce à des facteurs induisant une stimulation du système immunitaire ; (4) d’un effet protecteur des antécédents d’allergie sur le risque de LA de l’enfant. Les données analysées proviennent de l’étude cas-témoins française, ESTELLE, réalisée en 2010-2011. Les cas ont été identifiés par le Registre National des Hémopathies malignes de l’Enfant et les témoins ont été recrutés en population générale par téléphone, avec une stratification sur l’âge et le sexe. L’échantillon comportait 636 cas incidents de leucémie aiguë lymphoblastique (LAL), 100 cas incidents de leucémie aiguë myéloblastique (LAM), et 1421 témoins de moins de 15 ans. Les données ont été recueillies auprès des mères à l’aide d’un questionnaire téléphonique standardisé, identique pour les cas et les témoins. Les odds ratios (OR) ont été estimés par régression logistique non conditionnelle ajustée sur l’âge, le sexe, le niveau d’éducation maternel, la catégorie socio-professionnelle du foyer, et les facteurs de confusion potentiels. Nous n’avons pas observé d’augmentation du risque de LA chez les enfants dont la conception avait été difficile (OR=0,9[0,7-1,2]), ou avait nécessité la prise d'un traitement d’infertilité (OR=0,8[0,5-1,1]). La supplémentation préconceptionnelle en acide folique était inversement associée au risque de LA (OR=0,7[0,5-1,0]), sans spécificité de sous-type. Le risque de LAL était inversement associé aux infections banales avant l’âge de 1 an (OR=0,8[0,6-1,0]), à la fréquentation d’une crèche avant 1 an (OR=0,7[0,5-1,0]), à l'allaitement maternel (OR=0,8[0,7-1,0]) , et à des contacts réguliers avec les animaux domestiques à un âge précoce (OR=0,8[0,7-1,0]). En revanche, nous n’avons pas observé d’influence du mode d’accouchement sur le risque de LA. Enfin, les LA étaient inversement associées aux antécédents de rhinite allergique, d’eczéma, de dermatite atopique, d’allergie alimentaire; et d’asthme ou bronchite asthmatiforme traité par antihistaminique. Ces résultats ne sont pas en faveur d’un risque de LA associé aux techniques d’aide médicale à la procréation. Ils renforcent l’hypothèse d’un effet protecteur de la supplémentation préconceptionnelle en acide folique pour les LA. Enfin, ils apportent des arguments supplémentaires en faveur du rôle d’une stimulation précoce du système immunitaire dans la survenue des LAL. / The aim of this study was to investigate whether the following factors: 1) conception by assisted medical procreation (AMP), 2) maternal folic acid supplementation, 3) factors related to early stimulation of the immune system, and 4) the history of allergy were related to the risk of childhood acute leukemia (CL). The data were obtained from the national registry-based case-control study, Estelle, carried out in France in 2010-2011. Population controls were recruited by random digit dialing, with quotas on age and sex. The sample included 636 cases of acute lymphoblastic leukemia (ALL), 100 cases of acute myeloblastic leukemia (AML), and 1421 controls less the 15 years old and frequency matched on age and sex. The data were collected by telephone interview of the mothers, using the same standardized questionnaire for cases and controls. Odds ratios (OR) were estimated using unconditional regression models adjusted for age, sex, maternal education, parental socioeconomic status , and potential confounders. We did not observe any increase in CL risk in children who were conceived with difficulty (OR=0,9[0,7-1,2]) or with the use of any fertility treatments (OR=0,8[0,5-1,1]). Preconceptional folic acid supplementation was inversely associated with CL (OR=0,7[0,5-1,0]), without subtype-specificity. Early common infections before 1 year (OR=0,8[0,6-1,0]), attendance to day-care before 1 year (OR=0,7[0,5-1,0]), breastfeeding (OR=0,8[0,7-1,0]) and regular contact with pets in the first year (OR=0,8[0,7-1,0]) were inversely associated with ALL. However, the mode of delivery was not associated with ALL. Finally, reported history of eczema, atopic dermatitis, food allergy, allergic rhinitis, asthma or asthmatic bronchitis treated with anti-histaminic was inversely associated with CL. Our findings do not suggest that fertility treatments are risk factors for CL. They suggest that folic acid supplementation during pregnancy may reduce the risk of CL. They also support the hypothesis that some conditions promoting the maturation of the immune system may decrease the risk of ALL.

Na região do Vale do Ribeira, os resíduos de mineração foram dispostos diretamente sobre o solo, nas proximidades da empresa responsável pelo beneficiamento e fundição do minério de chumbo (Pb) (próximo à Vila Operária – município de Adrianópolis-PR). A escória de fundição enriquecida em metais potencialmente tóxicos (MPT), primeiramente foi disposta na forma de pilha. Em 2006, parte desta escória foi transferida para um aterro de resíduo sólido localizado a 50 m do antigo depósito e parte continuou no antigo local de disposição. As escórias que continuaram no antigo local foram espalhadas e cobertas com um solo residual. Esta cobertura não foi realizada de forma adequada, sendo que em algumas porções da área é possível ver as escórias, estando estas em contato direto com os animais (principalmente, ovinos e bovinos). Visando avaliar a influência da disposição das escórias na contaminação do solo de superfície e basal, foram coletadas amostras em distintas profundidades e em duas linhas de caminhamento principais (NS e EW) na área da antiga disposição. Nestas amostras foram realizadas caracterizações geotécnicas, geoquímicas e microbiológicas. Os ensaios realizados foram: granulometria conjunta, limites de Atterberg, capacidade de troca catiônica (CTC) e superfície específica (SE), matéria orgânica (MO), potencial hidrogeniônico (pH), potencial redox (Eh), condutividade elétrica (CE), delta pH (ΔpH), microscopia eletrônica de varredura com espectrômetro de energia dispersiva acoplado (MEV/EDS), mineralogia por difração de raios-x (DRX), fluorescência de raios-x (FRX), determinação da concentração pseudo-total (absorção atômica – AA; espectrometria de emissão atômica - ICP/AES), solubilização, lixiviação, extração sequencial, avaliação da comunidade microbiana por RCP-EEGD (ou PCR-DGGE) e sequenciamento do gene RNAr 16S via ILLUMINA. A avaliação da contaminação foi realizada considerando índice de geoacumulação (Igeo ), fator de enriquecimento (FE ou EF), Código de Avaliação de Risco (CAR ou RAC) e potencial de risco ecológico (Eir). O pH em H2O observado no depósito foi de 6,5 a 7,6, indicando que o meio é ligeiramente ácido. Já o Eh foi considerado oxidante. A CE foi especialmente elevada nas amostras superficiais (0-20 cm) e nos perfis coletados na linha de caminhamento EW. A CTC média foi de 14,3 cmolc/kg, sendo esta característica da caulinita. Quanto ao teor de matéria orgânica observou-se variação de 0,3 a 5,4 g/kg, sendo o valor médio de 2,14 g/kg. A base do depósito possui média de 68% de finos e índice de plasticidade de 2 a 35%. Para a base do depósito (de 60 a 100 cm) observou-se concentrações pseudo-totais de MPT bem inferiores ao topo. Em relação ao solo superficial observou-se elevada concentração pseudo-total, principalmente de Pb (média de 6.268,85 mg/kg) e Zn (média de 20.261,50 mg/kg). As concentrações de Cd observadas foram acima dos valores de background da área (média de 12,19 mg/kg). A concentração de MPT nas amostras coletadas na linha de caminhamento EW foram superiores às de NS, estando mais elevadas naquelas mais próximas à antiga empresa de beneficiamento. A partir dos ensaios de solubilização, lixiviação e extração sequencial, notou-se que o Pb e o Cd estão mais prontamente solúveis. Verificou-se para o Cd menor concentração pseudo-total, quando comparado com o Pb e Zn, todavia, observou-se para esse metal maior índice de geoacumulação, maior risco ecológico e maior mobilidade. A ordem obtida para os MPT, de acordo com o risco potencial, utilizando as frações mais móveis foi Cd > Pb ≈ Zn. Obteve-se maior diversidade e riqueza bacteriana nas amostras com maior concentração pseudo-total de metais, maior Igeo e maior Eir . Nas amostras superficiais foram identificadas bactérias tolerantes a presença de MPT, como Rhodoplanes, Kaistobacter, Sphingomonas, Flavobacterium, Cellvibrio, Rheinhermera e Pseudomonas. Assim, conclui-se que a porção superficial do perfil e mais próxima a empresa que beneficiou o minério está mais contaminada e com maior risco que a basal. A partir desses resultados pode-se inferir que a integração de conhecimentos é fundamental na avaliação da contaminação em áreas de mineração. / In the Ribeira Valley region, mining wastes were placed directly on the soil near the company responsible for the processing and smelting of lead ore (Pb) (near of the Vila Operária – Adrianópolis-PR). The slag enriched in potentially toxic metals (PTM) was initially deposited in piles. In 2006 part of the slag was moved to a solid waste landfill located 50 m from the old deposit and part remained at the former disposal site. The slag that remained in the old deposit were spread out evenly and covered with a residual soil. This coverage was not performed adequately, and in some areas of the deposit the slag is on the soil surface, being in direct contact with animals (mainly sheep and cattle). In order to assess the contamination of slag disposal on soil, samples were collected at various depths and in two main transverse lines (NS and EW) in the area of the old deposit. Geotechnical, geochemical and microbiological characterization were performed in these samples. The assays carried out were: granulometry, Atterberg limits, cation exchange capacity (CEC) and specific surface (SS), organic matter (OM) content, hydrogenation potential (pH), redox potential (Eh), electrical conductivity (EC), delta pH (ΔpH), scanning electron microscopy coupled with energy dispersive spectrometer (SEM/EDS), mineralogy using X-ray diffraction (XRD), x-ray fluorescence (XRF), determination of pseudo-total concentration (atomic absorption - AA; inductively coupled plasma atomic emission spectroscopy - ICP/AES), solubilization, leaching, sequential extraction, microbial community evaluation by PCR-DGGE and sequencing of the 16S RNAr gene via ILLUMINA. The evaluation of the contamination was conducted using the geoaccumulation index (Igeo), enrichment factor (EF), Risk Assessment Code (RAC) and potential ecological risk (Eir). The mean pH in H2O observed in the deposit varied from 6.5 to 7.6 (slightly acid) and Eh was considered oxidant. EC was especially high in the surficial samples (0-20 cm) and in the profiles collected in the EW transverse line. The medium CEC was 14.3 cmolc/kg, characteristic of kaolinite. The organic matter content varied from 0.3 to 5.4 g/kg, with a mean value of 2.14 g/kg. The base of the deposit is constituted with a medium of 68% of fines and plasticity index of 2-35%. It was observed that the base of the deposit (60 to 100 cm) has a considerably lower pseudo-total concentration of PTM when compared to the topsoil. In the surficial soil it was observed high pseudo-total concentration, mainly Pb (mean of 6,268.85 mg/kg) and Zn (mean of 20,261.50 mg/kg). The Cd concentrations were above the background values of the area (mean of 12.19 mg/kg). The PTM concentration in samples collected in the EW transverse line were higher than those of NS, being specially higher in the samples closer to the former beneficiation company. According to the results obtained from the solubilization, leaching and sequential extraction assays, it was noted that Pb and Cd are more readily soluble. A lower pseudo-total concentration was observed for Cd, when compared to Pb and Zn, however, a higher geoaccumulation index, greater ecological risk and greater mobility was observed for this metal. The order for PTM, according to the potential risk, using the more mobile fractions was Cd > Pb ≈ Zn. Greater diversity and bacterial richness were obtained in the samples with higher pseudo-total concentration of metals, higher Igeo and greater Eir. In the surficial samples, bacteria tolerant to the presence of PTM, such as Rhodoplanes, Kaistobacter, Sphingomonas, Flavobacterium, Cellvibrio, Rheinhermera and Pseudomonas were identified. Thus, it is concluded that the surface portion of the profile closer to the former smelting company is more contaminated and with greater risk than the basal portion. From the results it can be inferred that the integration of knowledge is fundamental in the evaluation of the contamination in mining areas.

L’iatrogénie induite par les erreurs médicamenteuses est un problème majeur de santé publique. Ce travail a pour objectif de développer une approche systémique visant à réduire leur occurrence en cancérologie. L’étude est menée aux Hospices Civils de Lyon au sein du Groupement Hospitalier Sud. L’analyse des erreurs médicamenteuses interceptées, sur une période de 5 ans, révèle que 4 prescriptions de chimiothérapie sur 100 présentent au moins une erreur médicamenteuse, dont plus de la moitié sont des erreurs de dose. Les facteurs de risque d’erreurs de prescription identifiés sont la prescription par un interne, l’hospitalisation conventionnelle, le patient ayant une surface corporelle supérieure à 2 m², les protocoles de plus de trois médicaments anticancéreux, comprenant du carboplatine ou nécessitant une modification par le prescripteur. L’évaluation de la gravité clinique potentielle des erreurs médicamenteuses montre que 13,4% d’entre elles auraient causé un préjudice temporaire et 2,6% un préjudice permanent. Le pronostic vital aurait été engagé dans 2,6% des cas conduisant au décès pour 6 patients sur une période d’un an. L’évaluation médico-économique permet d’estimer le coût pour l’assurance maladie d’une erreur médicamenteuse en cancérologie avec conséquences cliniques à 1 523€ associé à 3,5 journées d’hospitalisation supplémentaires. Cette approche systémique conduit au développement de revues d’erreurs médicamenteuses et de morbi-mortalité, socle de l’analyse collective indispensable à la prévention du risque médicamenteux en cancérologie / Medication errors are a major public health problem. This work aims to develop a systemic approach to reduce their occurrence in oncology. The study was conducted in Groupement Hospitalier Sud (Hospices Civils de Lyon). The analysis of intercepted medication errors, over a period of five years, reveals that four out of 100 prescriptions of chemotherapy include at least one medication error, which over half are dose errors. Risk factors of prescribing errors identified are prescription by a resident physician, inpatient care, patient with a body surface area greater than 2 m², protocol with more that three anticancer drugs, protocol involving carboplatin or protocol requiring at least one modification by the physician. 13.4% of avoided errors would have resulted in temporary injury and 2.6% in permanent damage. The vital prognosis of the patient would have been compromised in 2.6% of cases leading to death for six patients over a period of one year. The cost of one medication error with clinical consequences was estimated at € 1 523 associated to 3.5 additional days of hospitalisation. This approach led to the development of systematic medication errors reviews and morbi-mortality conferences that allow a collective and multidisciplinary analysis to enhance the patient’s safety

Les douleurs rachidiennes représentent un problème de santé important aux impacts socio-économique majeurs. Les rachialgies débutent tôt, durant l’enfance, leur prévalence augmente avec l’âge, particulièrement durant la période pubertaire, pour atteindre un niveau similaire à celui de l’âge adulte aux alentours de 20 ans. Malgré la fréquence de cette condition, les facteurs prédictifs du développement du premier épisode de douleur rachidienne ou d’un nouvel épisode sont très peu connus. Les travaux constitutifs de cette thèse ont pour objectif d’explorer différents facteurs prédictifs potentiels de douleurs rachidiennes chez les enfants et les adolescents. Une première revue de littérature a montré qu’il existe une association entre la puberté et les rachialgies. Les critères de causalité, décrits par Bradford-Hill, comme la force de l’association, la consistance entre les études et la relation dose-effet sont également présents. Cependant, il n’est pas encore possible de se prononcer sur le critère essentiel de la temporalité. La deuxième revue de littérature a permis de mettre en évidence une association positive entre l’endurance musculaire en extension et les douleurs rachidiennes, alors qu’aucune association n’a été mise en évidence entre la force musculaire en extension du tronc et les douleurs rachidiennes. Les données disponibles de la littérature ne permettent pas de ce prononcer concernant l’association entre les rachialgies et les capacités aérobies. La troisième étude, une étude prospective de suivi des enfants durant une année, n’a pas mis en évidence d’association entre les capacités aérobies, la composition corporelle et les douleurs au niveau du rachis. Deux facteurs sont donc associés aux douleurs rachidiennes, la puberté et une faible endurance musculaire. Les recherches dans ce domaine doivent êtres poursuivies pour déterminer l’existence d’un lien de causalité de ces facteurs sur les douleurs du rachis. / Spinal pain is a major health problem with socio-economic impacts. Back pain starts early, during childhood, the prevalence increases with age, particularly during puberty, to reach a similar level to that found at adulthood, around the age of 20. Despite the high prevalence of this condition, predictors for the first episode or for a recurrent episode are not known. The aim of this thesis is to explore different potential predictors of back pain during childhood and adolescence. A first literature review showed an association between puberty and back pain. The causality criteria described by Bradford- Hill, e.g. strength of the association, consistency across studies and dose -response are also present. Unfortunately,, it is not yet possible to conclude whether there is a temporal aspect as well; for temporality being the most important criterion. The second literature review showed a positive association between muscular endurance in extension and back pain, whereas no association was found between muscle strength in trunk extension and spinal pain. The available literature does not allow us to conclude about the potential association between aerobic capacity and back pain. The third study is a prospective study, in which children were followed during ten months. This study did not reveal any association between aerobic capacity, body composition and back pain. In conclusion, two factors are associated with back pain, puberty and low muscle endurance. Future research in this area should focus on the causal relationship between these factors and back pain.

行政院會於民國八十八年十二月十六日通過保險法修正草案，修正草案中針對強化保險業之監理機制與增進保戶大眾之權益係以強化其資本適足性為其修法目標，所採之方法即建立風險基礎資本額制（Risk-based Capital, RBC）。而保險法修正案於民國九十年六月二十六日業已經立法院三讀通過，基於保險法相關條文規定，RBC制度將於民國九十二年中實施。 另一方面，美國經濟、社會及投資環境和台灣不盡相同，若將此制度直接或稍加修改即套用於台灣，將可能造成不切實際與誤導的作用，其結果不僅可能無法有效規範及避免保險公司失卻清償能力，亦可能因而造成龐大的社會成本，反而和當初建立RBC制度之原意背道而馳。因此，本論文即依循台灣產險業之產業特性制訂一套合宜之產險RBC制度，其中包括各個適當之風險項目及所屬之風險係數。 本論文在資產風險部分結合風險值（Value at risk, VaR）來計算資產之風險係數；在準備金風險以及自留保費收入風險則依照美國RBC制度之原始公式重新計算得來，惟準備金風險部分實因資料取得限制無法順利求出，為求模型完整性此部分本論文以財政部草案取代之；而於自留保費收入風險方面是採險種別及公司別。 研究結果發現：台灣產險的風險係數確實和美國產險的風險係數是有相當的差異，並且須根據台灣產業的經驗及配合我國的社會、經濟、投資環境並經由實際的運算才能得到適切的風險係數；而以論文所建立之RBC模型試算於各公司之風險基礎資本比則多有偏低之情形。 / Legislative Yuan has pass the draft of Insurance Law on June 26, 2001. In order to strengthen insurance regulation mechanism and to protect the insureds' benefit, the Risk-based Capital will be implemented in Taiwan Insurance market in 2003. On the other way, the economic environment and investment markets in United State are different from those in Taiwan. If we directly imitate their RBC system in Taiwan, the outcome would be impractical. It not only can't regulate the insurers effectively, but also may cause huge social cost. Therefore, the purpose of the thesis is to establish a suitable risk items and suitable risk factors for Property-Liability insurance in Taiwan by our own empirical data. This study finds that risk factors are significant different between Taiwan and American for Property-Liability insurance industry. The risk factors of the RBC system in Taiwan must depend on our own empirical data. I used the RBC model built in the thesis to test every Property-Liability company in Taiwan, and found that calculated Risk-based Capital ratios were relatively low.

<p>Abdominal aortic aneurysm (AAA) is a common problem with life-threatening consequences and was suspected to be a serious health problem in Norsjö, a municipality in northern Sweden. A screening study was undertaken to investigate the prevalence, risk factors associated with AAA and the effect of screening on quality of life (QoL). All men and women, aged 65-75 years, were invited to an ultrasonography (US) examination, 91% attended and 92 subjects were also evaluated with computed tomography (CT).</p><p>Depending on diagnostic criteria, the AAA prevalence was 3.6-16.9% in men and 0.8-9.4% in women. Seventy-five percent of the differences between US- and CT anteroposterior measurements were less than 5 mm. A decrease in mental health was observed among AAA patients with low baseline SF-36 scale scores. Elevated cholesterol at age 60 years were associated with screening detected AAA after 12 years of follow-up. Smoking, atherosclerosis and having a first degree relative with AAA were associated with AAA at screening. Compared to blood samples obtained 12 years prior to screening an elevation of hsCRP over time was observed among AAA patients. </p><p>Based on a systematic review of the literature, different screening strategies were analysed in a Markov cohort model. The cost per life year gained ranged from $8 309 to $14 084 and was estimated to $10 474 when 65 year old men were screened once.</p><p>Conclusions: The highest prevalence of AAA ever reported, in a population-based screening program, was found in Norsjö. The risk of having an AAA at screening showed a strong but complex association with atherosclerosis and its risk factors, genetic and inflammatory mechanisms may also be important. Screening 65-year-old men for AAA may be cost-effective, but QoL aspects on the cost-effectiveness of AAA screening merits further investigation.</p>