Os sistemas de farmacovigilância fundamentam as decisões sobre segurança no uso de medicamentos regulamentados por autoridades de saúde. Estudá-los e propor estratégias de melhorias contribuem para fortalecer os sistemas de saúde, aperfeiçoando a qualidade da assistência à saúde e assegurando a segurança do paciente e coletividade. A Tese objetivou analisar a evolução e desempenho do sistema brasileiro de farmacovigilância, denominado de SINAF, e as notificações dos pacientes com suspeitas de reações adversas a medicamentos (RAMs) registradas no Notivisa-medicamento no período de 2008 a 2013 e propor uma lista-referência de códigos da CID-10 para vigilância de RAMs e intoxicações medicamentosas (IMs). A Tese compreende seis artigos científicos organizados para publicação. No primeiro, uma revisão de escopo apresentou uma perspectiva histórica para caracterizar a evolução do SINAF e lacunas identificadas no processo, como a ausência de comissão de farmacovigilância que atenda aos requisitos mínimos de um sistema de farmacovigilância propostos pela Organização Mundial da Saúde. Os artigos 2, 3 e 4 analisaram características relacionadas com o desempenho do SINAF. O artigo 2 revelou que não há preferência digital da idade na base de dados das notificações de eventos adversos a medicamentos (EAMs) do Notivisa-medicamento. Mediante uma análise comparativa, o artigo 3 mostrou diferenças entre o formulário para notificação de EAMs utilizado no SINAF e de outros doze países latinoamericanos (Argentina, Bolívia, Chile, Colômbia, Costa Rica, Cuba, Guatemala, México, Panamá, Peru, Uruguai e Venezuela), sobretudo na quantidade de variáveis para preenchimento, podendo contribuir com a subnotificação de casos. No artigo 4 – um estudo de avaliação de sistemas de vigilância de saúde pública –, revelou que o desempenho do Notivisa-medicamento foi considerado satisfatório para três atributos (flexibilidade, validade e erro preditivo positivo) e deficitário para a maioria deles (simplicidade, aceitabilidade, representatividade, completude, consistência, oportunidade e clareza metodológica). O artigo 5, mediante estudo descritivo e retrospectivo, encontrou uma taxa de notificação de RAMs de 22,8/ 1 milhão de habitantes/ano. Trata-se de taxa bastante inferior a países de alta renda como Nova Zelândia, Suécia, Austrália e Suíça que possuem mais de 300 notificações por milhão, como em relação a países de média renda, como a África do Sul, com taxa de 77 por milhão de habitantes. A população feminina (60,5%) prevaleceu no total de pacientes (26.554), assim como, a raça/cor branca (58,1%). A idade variou de 0 a 112 anos (mediana = 46 anos). Quase 1/3 (32,5%) das suspeitas de RAMs ocorreram em populações vulneráveis (idosos e crianças). Foram avaliados 54.288 pares de medicamento-reação adversa, onde prevaleceram as reações adversas graves (59,2%), com destaque para as que resultaram em efeito clinicamente importante (83,1%). O estudo 6 propôs uma lista-referência com 691 códigos da CID-10, sendo 360 (52,1%) relacionados com RAMs e 331 (47,9%) com IMs. Um total de 511 (73,9%) códigos estão relacionados com casos de admissão hospitalar e/ou óbito. Os achados da Tese evidenciam a necessidade de mudanças em diferentes aspectos estudados do SINAF, como forma de contribuir na produção de informações completas, fidedignas e mais representativas sobre danos ocasionados por medicamentos comercializados no país. / The pharmacovigilance systems support the decisions on safety when using medications regulated by health authorities. Analyzing them and proposing improvement strategies are ways to make healthcare systems stronger, improving the quality of healthcare assistance, making sure the patient is safe and that the population is ensured. The dissertation was aimed at analyzing the evolution and performance of the Brazilian pharmacovigilance system, SINAF, and the notification of patients with suspected adverse drug reactions (ADRs) registered with the notification system NOTIVISA/medication from 2008 through 2013, as well as proposing a reference list of ICD-10 codes for surveillance of ADRs and intoxication due to medication (IDM). The dissertation is comprised of six scientific articles ready to be published. The first one, a scoping review, presents a historical perspective to demonstrate the development process of SINAF and the gaps identified during the process, such as the absence of a pharmacovigilance commission that complies with the minimum requirements of a pharmacovigilance system as proposed by World Health Organization. Articles 2, 3 and 4 presents an analysis of the performance-related characteristics of SINAF. Article 2 reveals that there is no digital age preference in the adverse drug events (ADEs) database belonging to NOTIVISA/medication. Using a comparative analysis, article 3 shows differences between the form for ADEs notification using SINAF and in other twelve Latin-American countries (Bolivia, Chile, Colombia, Costa Rica, Cuba, Guatemala, Mexico, Panama, Peru, Uruguay and Venezuela), highlighting the number of variables to complete, and it may collaborate with the sub-notification of cases. Article 4 – a study on the evaluation of public health surveillance systems over time – reveal that the performance of NOTIVISA/medication was considered satisfactory regarding three attributes (flexibility, validity and positive predictive error) and deficient regarding most of the others (simplicity, acceptability, representability, integrality, consistency, opportunity and methodological clarity). Article 5, by means of a descriptive and retrospective study, found an ADR notification rate of 22.8/million inhabitants/year. This is a much lower rate than in high income countries, such as New Zealand, Sweden, Australia and Switzerland, which have over 300 notifications per million, when compared against average income, such as South Africa, with a rate of 77/million inhabitants. Female population (60.5%) prevailed in the total number of patients (26,554), as well as white race/color (58.1%). Age was between 0 - 112 years old (median = 46 years). Almost 1/3 (32.5%) of the suspected ADRs occurred in vulnerable populations (elderly and children). 54,288 pairs of medication/adverse reactions were assessed. Severe adverse reactions prevailed (59.2%), and attention is drawn to those resulting in clinically important effect (83.1%). Study 6 proposes a reference list with 691 ICD-10 codes; 360 (52.1%) out of them are ADRs-related and 331 (47.9%) out of them are IDM. A total of 511 (73.9%) codes are related to cases of hospital admission and/or death. The dissertation findings prove the need of changes across different aspects in SINAF as a way to contribute to production of complete, reliable and representative information on damages caused by commercially available drugs in Brazil.

Introdução: Eventos adversos a medicamentos (EAM) representam um importante problema de saúde pública, sendo associados à morbimortalidade, maior taxa de permanência hospitalar e elevação de custos. Os idosos e os pacientes de unidade de terapia intensiva (UTI) são grupos de risco para a ocorrência desses eventos. O uso de rastreadores, que representam situações indicativas de potenciais EAM, simplifica a detecção de EAM por meio do screening sistemático de prontuários, possibilitando a mensuração da taxa dessas adversidades continuamente e permitindo avançar na prática de segurança do paciente crítico. Objetivo: Analisar os eventos adversos a medicamentos e fatores associados em pacientes idosos de UTI. Método: Coorte retrospectiva conduzida com idosos internados em UTI do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A amostra consecutiva foi composta por prontuários de idosos, hospitalizados por no mínimo 24 horas para tratamento clínico ou cirúrgico e que tenham recebido pelo menos um medicamento. Os pacientes foram acompanhados da internação até a saída da UTI por alta ou óbito. Para a identificação dos EAM utilizou-se o instrumento do Institute for Healthcare Improvement (IHI) adaptado para a realidade local, que inclui rastreadores medicamentosos, bioquímicos e clínicos. Foram coletadas variáveis demográfico-clínicas, relativas ao regime terapêutico, exames laboratoriais, intervenções durante a internação e sinais/sintomas clínicos. A variável dependente foi a ocorrência de EAM. Os dados foram analisados por meio dos testes Qui-quadrado, Exato de Fisher, Correlação de Pearson e regressão logística multivariada, com significância de p0,05. Resultados: A incidência de pacientes com EAM foi 22,3% e o número de EAM por 100 pacientes foi 32,3, média de 1,4 EAM. A amostra foi composta predominantemente por homens (54,6%), idosos jovens (68,8%), internados para procedimentos clínicos (67,4%) e sujeitos a polifarmácia (70,6%). Sangramento (21,7%), injúria renal aguda (20%), hipotensão (18,3%), náusea/vômito (15%) e hipoglicemia (13,3%) foram os EAM mais frequentes. Identificou-se correlação positiva entre EAM e as variáveis comorbidades (r=0,189), tempo de internação (r=0,288) e número de medicamentos prescritos (r=0,282). Os fatores de risco para EAM em UTI foram ventilação mecânica (OR= 2,614; IC95% 1,393 4,906; p= 0,003), injúria renal aguda (OR= 3,794; IC95% 1,688 8,527; p=0,001) e diabetes mellitus (OR= 3,280; IC 95% 1,703 6,315; p= 0,000). Conclusão: A ocorrência dos EAM mostrou-se correlacionada positivamente com atributos que são muito característicos de idosos admitidos em UTI, aspecto que pode servir de alerta aos profissionais que realizam o monitoramento desses eventos. / Introduction: Adverse drug events (ADE) represent an important public health problem, being associated with morbidity and mortality, a higher hospital stay rate and higher costs. The elderly and intensive care patients (ICU) are at risk groups for the occurrence of these events. The use of trackers, which represent situations indicative of potential ADE, simplifies the detection of ADE through the systematic screening of medical records, making it possible to measure the rate of these adversities continuously and to advance in the practice of critical patient safety. Objective: To analyze adverse drug events and associated factors in elderly ICU patients. Method: Retrospective cohort conducted with elderly patients admitted to ICU at Hospital das Clínicas, Medical School, University of São Paulo. The consecutive sample consisted of records of the elderly, hospitalized for at least 24 hours for clinical or surgical treatment and who received at least one medication. Patients were followed up for ICU discharge or discharge. The Institute for Healthcare Improvement (IHI) instrument adapted to the local reality, which includes drug, biochemical and clinical trackers, was used to identify the ADE. Demographic and clinical variables related to the therapeutic regimen and laboratory tests, therapeutic interventions during hospitalization, clinical signs and symptoms were collected. The dependent variable was the occurrence of ADE. Data were analyzed using the Chi-square test, Fisher\'s exact test, Pearson\'s correlation and multivariate logistic regression, with significance of p0.05. Results: The incidence of ADE patients was 22.3% and the number of ADE per 100 patients was 32.3, a mean of 1.4 ADE. Men (54.6%), young adults (68.8%), hospitalized for clinical procedures (67.4%) and polypharmacy (70.6%). Bleeding (21.7%), acute renal injury (20%), hypotension (18.3%), nausea / vomiting (15%) and hypoglycaemia (13.3%) were the most frequent events. A positive correlation between EAM and comorbidities (r = 0.189), length of hospital stay (r = 0.288), and number of drugs prescribed (r=0.282) were identified. The risk factors for EAM in the ICU were mechanical ventilation (OR= 2,614; IC95%, 1,393 4,906; p= 0,003), acute renal injury (OR= 3,794; IC95% 1,688 8,527; p=0,001) and diabetes mellitus (OR= 3,280; IC 95% 1,703 6, 315; p= 0,000). Conclusion: The occurrence of ADE was positively correlated with attributes that are very characteristic of the elderly admitted to the ICU, an aspect that can serve as an alert to the professionals who perform the monitoring of these events.

Introdução: Vancomicina, considerada o antibiótico de primeira escolha para o tratamento de infecções estafilocócicas, é eliminada por filtração glomerular, e a sua administração deve ser individualizada de acordo com a função renal. As diretrizes atuais recomendam doses e níveis séricos maiores, para aumentar as chances de bons resultados clínicos. Questiona-se se esta estratégia causaria maior nefrotoxicidade. Objetivos: Comparar a frequência de injúria renal aguda (IRA) em pacientes com suspeita de infecção estafilocócica tratados com vancomicina ou com outros antimicrobianos com o mesmo perfil terapêutico em um hospital terciário. Analisar a associação do uso de vancomicina com o desenvolvimento de IRA nestes pacientes. Avaliar os fatores de risco associados ao desenvolvimento de IRA nos pacientes tratados com vancomicina. Identificar os fatores de risco associados à letalidade precoce e tardia nos pacientes com suspeita de infecção estafilocócica tratados com vancomicina ou outros antimicrobianos com o mesmo perfil terapêutico. Métodos: Foram analisados os prontuários dos pacientes com suspeita de infecção estafilocócica que receberam os antimicrobianos vancomicina, teicoplanina, oxacilina, daptomicina ou linezolida por pelo menos três dias nos anos de 2010 e 2011 em um hospital terciário. Analisou-se a frequência de IRA associada ao uso de vancomicina (critério KDIGO) e. por regressão logística, se o uso de vancomicina foi associado ao desenvolvimento de IRA. Avaliou-se por regressão logística os fatores de risco associados ao desenvolvimento de IRA no grupo de pacientes tratados com vancomicina. Analisou-se por regressão de Cox os fatores de risco para letalidades intra-hospitalar, seis meses e até um ano após a internação. Resultados: Foram incluídos 591 pacientes, dos quais 508 foram expostos à vancomicina e 83 foram expostos a teicoplanina, oxacilina, linezolida, ou daptomicina. IRA ocorreu em 28,5% dos pacientes que utilizaram vancomicina e em 14,5% dos que utilizaram outros antimicrobianos (p < 0,001). O grupo de pacientes tratados com vancomicina apresentou parâmetros sugestivos de maior gravidade, como maior frequência de culturas positivas para estafilococos, hipotensão grave, contagem de leucócitos em sangue periférico mais elevada e níveis séricos maiores de lactato, procalcitonina e PCR. Quando pacientes que desenvolveram IRA foram comparados com pacientes que mantiveram a função renal estável, observou-se que o uso de vancomicina, a duração do tratamento e nível sérico de vancomicina foram significativamente maiores entre os primeiros. Vancomicina foi identificada como fator independente para o desenvolvimento de IRA na regressão logística. Os fatores de riscos independentes para o desenvolvimento de IRA no grupo exposto à vancomicina foram uso de medicamentos nefrotóxicos ou que alteram a função renal, uso de medicamento vasopressor e concentração sérica de vancomicina >= 20 mg/L. Vancomicina não se associou a letalidade em nenhum dos períodos estudados, enquanto IRA se associou de forma independente à letalidade precoce e tardia. Conclusões: Estes resultados indicam que a vancomicina apresenta nefrotoxicidade significativa e que os seus níveis séricos devem ser obrigatoriamente avaliados. O uso de medicamentos nefrotóxicos ou que alteram a função renal deve ser, quando possível, evitado ou suspenso em pacientes tratados com vancomicina. O desenvolvimento de IRA, mas não o uso de vancomicina, foi fator independente para letalidade, reforçando que este antimicrobiano pode ser utilizado quando indicado, desde que se previna o desenvolvimento de IRA / Introduction: Vancomycin is considered the first choice antibiotic for treatment of staphylococcus infection. Vancomycin is eliminated through glomerular filtration, and so it is administration must be individualized according the renal function. Current treatment guidelines recommend higher doses and blood levels in order to increase the odds for an adequate clinical outcome. On the other hand, this strategy might cause higher vancomycin-associated nephrotoxicity. Objectives: To analyze the frequency of acute kidney injury (AKI) development in patients with suspicion of staphylococcus infection treated with vancomycin, or other antibiotics with the same therapeutic profile in a tertiary hospital. To analyze the association of vancomycin with AKI development in those patients. To analyze the risk factors for AKI development in vancomycin-treated patients. To identify the risk factors associated to early and late mortality in patients with suspicion of staphylococcus infection treated with vancomycin, or other antibiotics with the same therapeutic profile in a tertiary hospital.Methodology:We analyzed the files of all the patients with suspicion of staphylococcus infection treated with vancomycin, teicoplanin, oxacillin, daptomycin, or linezolid antibiotics for at least three days during the years of 2010 and 2011 in a tertiary hospital.The frequency of AKI development (KDIGO criteria) was assessed. Using logistic regression we assessed if vancomycin use was an independent risk factor for AKI development and the risk factors for AKI development in the group of patients treated with vancomycin. We assessed, using Cox regression, the risk factors for in-hospital, six months and one year after hospitalization mortality. Results: We included 591 patients in the final analysis, 508 using vancomycin and 83 using other antibiotics (teicoplanin, oxacillin, daptomycin, or linezolid). AKI developed in 28.5% of the vancomycin group compared with 14.5% in the other antibiotics group (p < 0.001). Patients treated with vancomycin showed parameters suggesting higher clinical severity, such as higher percent of staphylococcus positive cultures, severe hypotension, higher leukocytes blood count, higher serum levels of lactate, procalcitonin and CRP. When patients developing AKI were compared with patients maintaining preserved renal function, the first group showed a statistically significant higher frequency of vancomycin use, longer vancomycin treatment and higher vancomycin through levels. Using logistic regression vancomycin was identified as an independent risk factor for AKI development. The independent risk factors for AKI development in the vancomycin group were simultaneous use of vancomycin and other nephrotoxic drugs or drugs that influence renal function, vasopressor drugs use and blood levels of vancomycin >= 20 mg/L. Vancomycin was not associated with mortality in any studied time, whereas AKI was an independent risk factor for early and late mortality. Conclusions: These results indicate that vancomycin is associated with significative nephrotoxicity and that its blood levels must be mandatorily assessed. The use of drugs that are nephrotoxic or influence renal function must be, when feasible, avoided or halted in vancomycin-treated patients. AKI development, but not vancomycin use, was an independent risk factor for mortality, reinforcing the perception that vancomycin can be used when necessary, since AKI development is prevented

Diploma thesis is focused on specifications in pharmaceutical business. It is based on knowledge of pharmacy and economy and their synthesis is describing the most significant differences in pharmacy business and other markets. Overall goal of diploma thesis was to create overview about pharmaceutical industry, its progress, trends and behavior of companies to this high risk and volatile market with keeping the rules and norms of Czech and European authorities. Target was also to form group of recommendations for companies participated in this market. To keep this target I described in the first part of diploma thesis basic terminology and theoretical knowledge about pharmaceutical market including research and development, marketing and sales and pharmakovigilance. Practical part was based on case studies specifying the most common and difficult problems and steps leading to their solutions. My personal contribution in diploma thesis is based on detailed and professional handling of the topic and in the choice of parametres which influence the most timing and capital demands of R&D projects in pharmacy and mitigation of their negative aspects.

La dématérialisation des données de santé a permis depuis plusieurs années de constituer un véritable gisement de données provenant de tous les domaines de la santé. Ces données ont pour caractéristiques d’être très hétérogènes et d’être produites à différentes échelles et dans différents domaines. Leur réutilisation dans le cadre de la recherche clinique, de la santé publique ou encore de la prise en charge des patients implique de développer des approches adaptées reposant sur les méthodes issues de la science des données. L’objectif de cette thèse est d’évaluer au travers de trois cas d’usage, quels sont les enjeux actuels ainsi que la place des data sciences pour l’exploitation des données massives en santé. La démarche utilisée pour répondre à cet objectif consiste dans une première partie à exposer les caractéristiques des données massives en santé et les aspects techniques liés à leur réutilisation. La seconde partie expose les aspects organisationnels permettant l’exploitation et le partage des données massives en santé. La troisième partie décrit les grandes approches méthodologiques en science des données appliquées actuellement au domaine de la santé. Enfin, la quatrième partie illustre au travers de trois exemples l’apport de ces méthodes dans les champs suivant : la surveillance syndromique, la pharmacovigilance et la recherche clinique. Nous discutons enfin les limites et enjeux de la science des données dans le cadre de la réutilisation des données massives en santé. / The dematerialization of health data, which started several years ago, now generates na huge amount of data produced by all actors of health. These data have the characteristics of being very heterogeneous and of being produced at different scales and in different domains. Their reuse in the context of clinical research, public health or patient care involves developing appropriate approaches based on methods from data science. The aim of this thesis is to evaluate, through three use cases, what are the current issues as well as the place of data sciences regarding the reuse of massive health data. To meet this objective, the first section exposes the characteristics of health big data and the technical aspects related to their reuse. The second section presents the organizational aspects for the exploitation and sharing of health big data. The third section describes the main methodological approaches in data sciences currently applied in the field of health. Finally, the fourth section illustrates, through three use cases, the contribution of these methods in the following fields: syndromic surveillance, pharmacovigilance and clinical research. Finally, we discuss the limits and challenges of data science in the context of health big data.

No description available.

Medical research requires detailed and accurate information on individual patients. This is especially so in the context of pharmacovigilance which amongst others seeks to identify previously unknown adverse drug reactions. Here, the clinical stories are often the starting point for assessing whether there is a causal relationship between the drug and the suspected adverse reaction. Reliable automatic de-identification of medical case narratives could allow to share this patient data without compromising the patient’s privacy. Current research on de-identification focused on solving the task of labelling the tokens in a narrative with the class of sensitive information they belong to. In this Master’s thesis project, we explore an inverse approach to the task of de-identification. This means that de-identification of medical case narratives is instead understood as identifying tokens which do not need to be removed from the text in order to ensure patient confidentiality. Our results show that this approach can lead to a more reliable method in terms of higher recall. We achieve a recall of sensitive information of 99.1% while the precision is kept above 51% for the 2014-i2b2 benchmark data set. The model was also fine-tuned on case narratives from reports of suspected adverse drug reactions, where a recall of sensitive information of more than 99% was achieved. Although the precision was only at a level of 55%, which is lower than in comparable systems, an expert could still identify information which would be useful for causality assessment in pharmacovigilance in most of the case narratives which were de-identified with our method. In more than 50% of the case narratives no information useful for causality assessment was missing at all. / Tillgång till detaljerade kliniska data är en förutsättning för att bedriva medicinsk forskning och i förlängningen hjälpa patienter. Säker avidentifiering av medicinska fallbeskrivningar kan göra det möjligt att dela sådan information utan att äventyra patienters skydd av personliga data. Tidigare forskning inom området har sökt angripa problemet genom att märka ord i en text med vilken typ av känslig information de förmedlar. I detta examensarbete utforskar vi möjligheten att angripa problemet på omvänt vis genom att identifiera de ord som inte behöver avlägsnas för att säkerställa skydd av känslig patientinformation. Våra resultat visar att detta kan avidentifiera en större andel av den känsliga informationen: 99,1% av all känslig information avidentifieras med vår metod, samtidigt som 51% av alla uteslutna ord verkligen förmedlar känslig information, vilket undersökts för 2014-i2b2 jämförelse datamängden. Algoritmen anpassades även till fallbeskrivningar från biverkningsrapporter, och i detta fall avidentifierades 99,1% av all känslig information medan 55% av alla uteslutna ord förmedlar känslig information. Även om denna senare andel är lägre än för jämförbara system så kunde en expert hitta information som är användbar för kausalitetsvärdering i flertalet av de avidentifierade rapporterna; i mer än hälften av de avidentifierade fallbeskrivningarna saknades ingen information med värde för kausalitetsvärdering.

The Health Sector at the state of Kuwait is facing many challenges. One of which is public expectations in health are high, and thus, the Ministry of Health (MOH) in Kuwait has amplified the health expenditure by 86% since 2007. And since the medicine budget represents half of the total MOH budget, it is proposed that the development in health policy might be a suitable tool to control the inflation within the health budget. This thesis examines the opportunities and challenges of introducing an EML in Kuwait and the factors influencing its effectiveness. A mixed-methodology approach has been used to enhance and validate the data, in the form of interviews, comparative studies and questionnaires. One major limitation to the research was the lack of previous data relating to this work, and the information should be gathered in person in the form of hard copies, and later, the data was analysed using qualitative and quantitative approaches. It has been attained that, the EML might be a valuable tool if adopted and implemented appropriately, EML adjustment to country health situation is crucial for successful utilisation and fulfilling the concept objectives. Standard Treatment Guidelines are fundamental part of EM selection process, in Kuwait there were lack in the uniformity of the local STG, but fortunately, there is an eagerness to innovate, and the medicine situation might benefit from a type of organisation, overall, if the EML implemented efficiently in Kuwait, it might help in improving the general health and control the inflation in MOH budget.

Le bilan comparatif des médicaments (BCM) constitue une pratique organisationnelle requise par Agrément Canada. Alors que la contribution des médecins et pharmaciens est bien définie, celle des infirmières demeure à préciser. But : Décrire l’implication infirmière dans la mise en œuvre du BCM auprès d’une clientèle atteinte de problèmes cardiaques admise à l’unité de cardiologie d’un centre hospitalier. Méthode : Étude de cas unique avec entretiens (N = 6) (infirmières, médecins, pharmaciens), revue qualitative de dossiers patients (N = 22) et sources documentaires (N =15), s’appuyant sur un cadre de référence intégrateur. Résultats : L’implication infirmière va au-delà des attentes relatives à la seule gestion du formulaire. L’implication effective se traduit par quatre catégories : propre et distinctive, mobilisation nuancée, filet de sûreté et activités contributives. Conclusion : L’accompagnement des patients et la mobilisation des autres professionnels révèlent une implication de l’infirmière dans le BCM qui gagne à être reconnue. / Medication reconciliation (MedRec) is a formal process. While doctors’ and pharmacists’ contribution is clearly spelled out, nurses’ involvement remains to be clarified. Goal: Describe nurses’ involvement in implementing MedRec among cardiorespiratory patients admitted to a hospital centre’s cardiology department. Framework: Meleis theory, Reason model. Method: Single case study. Three data sources: interviews (N = 6) (nurses, doctors and pharmacists); a qualitative review of patient files (N = 22), and documentation (N =15). Results: While nurses are indeed expected to manage forms in the various phases of transition of care, their involvement extends well beyond this task and falls into four main categories: distinct involvement; nuanced mobilization; safety net, and; contributive activities. Results show that the accompaniment of patients and their loved ones is learned through teaching, screening high-risk patients and collaborating in a way that supports the mobilization of the other professionals involved to ensure patient safety during transitions.

Ce travail de thèse porte sur l'estimation paramétrique du maximum de vraisemblance pour des données de survie tronquées à droite, lorsque les délais de troncature sont considérés déterministes. Il a été motivé par le problème de la modélisation des délais de survenue des effets indésirables médicamenteux à partir des bases de données de pharmacovigilance, constituées des cas notifiés. Les distributions exponentielle, de Weibull et log-logistique ont été explorées.Parfois le caractère tronqué à droite des données est ignoré et un estimateur naïf est utilisé à la place de l'estimateur pertinent. Une première étude de simulations a montré que, bien que ces deux estimateurs - naïf et basé sur la troncature à droite - puissent être positivement biaisés, le biais de l'estimateur basé sur la troncature est bien moindre que celui de l'estimateur naïf et il en va de même pour l'erreur quadratique moyenne. De plus, le biais et l'erreur quadratique moyenne de l'estimateur basé sur la troncature à droite diminuent nettement avec l'augmentation de la taille d'échantillon, ce qui n'est pas le cas de l'estimateur naïf. Les propriétés asymptotiques de l'estimateur paramétrique du maximum de vraisemblance ont été étudiées. Sous certaines conditions, suffisantes, cet estimateur est consistant et asymptotiquement normal. La matrice de covariance asymptotique a été détaillée. Quand le délai de survenue est modélisé par la loi exponentielle, une condition d'existence de l'estimation du maximum de vraisemblance, assurant ces conditions suffisantes, a été obtenue. Pour les deux autres lois, une condition d'existence de l'estimation du maximum de vraisemblance a été conjecturée.A partir des propriétés asymptotiques de cet estimateur paramétrique, les intervalles de confiance de type Wald et de la vraisemblance profilée ont été calculés. Une seconde étude de simulations a montré que la couverture des intervalles de confiance de type Wald pouvait être bien moindre que le niveau attendu en raison du biais de l'estimateur du paramètre de la distribution, d'un écart à la normalité et d'un biais de l'estimateur de la variance asymptotique. Dans ces cas-là, la couverture des intervalles de la vraisemblance profilée est meilleure.Quelques procédures d'adéquation adaptées aux données tronquées à droite ont été présentées. On distingue des procédures graphiques et des tests d'adéquation. Ces procédures permettent de vérifier l'adéquation des données aux différents modèles envisagés.Enfin, un jeu de données réelles constitué de 64 cas de lymphomes consécutifs à un traitement anti TNF-α issus de la base de pharmacovigilance française a été analysé, illustrant ainsi l'intérêt des méthodes développées. Bien que ces travaux aient été menés dans le cadre de la pharmacovigilance, les développements théoriques et les résultats des simulations peuvent être utilisés pour toute analyse rétrospective réalisée à partir d'un registre de cas, où les données sur un délai de survenue sont aussi tronquées à droite. / This work investigates the parametric maximum likelihood estimation for right-truncated survival data when the truncation times are considered deterministic. It was motivated by the modeling problem of the adverse drug reactions time-to-onset from spontaneous reporting databases. The families of the exponential, Weibull and log-logistic distributions were explored.Sometimes, right-truncation features of spontaneous reports are not taken into account and a naive estimator is used instead of the truncation-based estimator. Even if the naive and truncation-based estimators may be positively biased, a first simulation study showed that the bias of the truncation-based estimator is always smaller than the naive one and this is also true for the mean squared error. Furthermore, when the sample size increases, the bias and the mean squared error are almost constant for the naive estimator while they decrease clearly for the truncation-based estimator.Asymptotic properties of the truncation-based estimator were studied. Under sufficient conditions, this parametric truncation-based estimator is consistent and asymptotically normally distributed. The covariance matrix was detailed. When the time-to-onset is exponentially distributed, these sufficient conditions are checked as soon as a condition for the maximum likelihood estimation existence is satisfied. When the time-to-onset is Weibull or log-logistic distributed, a condition for the maximum likelihood estimation existence was conjectured.The asymptotic distribution of the maximum likelihood estimator makes it possible to derive Wald-type and profile likelihood confidence intervals for the distribution parameters. A second simulation study showed that the estimated coverage probability of the Wald-type confidence intervals could be far from the expected level because of a bias of the parametric maximum likelihood estimator, a gap from the gaussian distribution and a bias of the asymptotic variance estimator. In these cases, the profile likelihood confidence intervals perform better.Some goodness-of-fit procedures adapted to right-truncated data are presented. Graphical procedures and goodness-of-fit tests may be distinguished. These procedures make it possible to check the fit of different parametric families to the data.Illustrating the developed methods, a real dataset of 64 cases of lymphoma, that occurred after anti TNF-α treatment and that were reported to the French pharmacovigilance, was finally analyzed. Whilst an application to pharmacovigilance was led, the theoretical developments and the results of the simulation study may be used for any retrospective analysis from case registries where data are right-truncated.