Sub-notificação de reacções adversas medicamentosas : um problema com solução? : contribuição para o conhecimento da sub-notificação de RAMs em Portugal e implementação de medidas minimizadoras do impacte

RESUMO - Introdução: As Reacções Adversas Medicamentosas (RAMs) constituem um grave problema de Saúde Pública em termos da mortalidade e morbilidade provocadas, tendo também um impacto económico considerável nos Sistemas de Saúde. Os Sistemas de Notificacão Espontânea de RAMs são considerados como o método de vigilância de medicamentos mais eficaz, sendo a sub-notificação de RAMs uma das suas maiores limitações. Em termos globais, foi estimado que apenas 6% de todas as reacções adversas são notificadas. Portugal apresenta uma taxa de notificação de RAMs relativamente baixa quando comparada com os países mais notificadores da Europa. São objectivos deste estudo: 1) caracterizar as atitudes e os comportamentos dos médicos, dos farmacêuticos e dos enfermeiros em Portugal Continental relativamente à notificação de RAMs; e 2) caracterizar a efectividade de intervenções educacionais destinadas a reduzir a sub-notificação de RAMs. Métodos: Numa primeira fase será efectuado um estudo de caso-controlo em médicos, farmacêuticos e enfermeiros de Portugal Continental, a exercer actividade no Servico Nacional de Saúde (SNS), de modo a caracterizar as suas atitudes e comportamentos relativamente à notificação de RAMs. Como casos serão considerados os Profissionais de Saúde que notificaram pelo menos uma RAM num determinado período e os controlos os Profissionais de Saúde que não notificaram qualquer RAM nesse mesmo período, sendo estes útimos seleccionados aleatoriamente. O estudo será conduzido através de um questionário de auto-resposta, em que as questões relativas às atitudes e comportamentos são baseadas nos “sete pecados mortais” de Inman. Será utilizada uma Escala Visual Analógica para registar as respostas, podendo estas ir de zero (totalmente em desacordo) até 10 (totalmente de acordo). Será utilizada uma análise de regressão logística para determinar o odds ratio ajustado (ORadj) da notificação de RAMs para uma mudança de exposição correspondente ao range interquartil para cada atitude. Numa segunda fase, será efectuado ensaio aleatorizado controlado de cluster, para caracterizar a efectividade das intervenções educacionais realizadas sobre as causas identificadas na primeira parte do trabalho, com o intuito de reduzir a sub-notificação de RAMs. Com base em informacão de 2007 foram identificados 43 clusters dispersos pelas várias Regiões de Saúde. As intervenções educacionais são compostas por uma apresentação com uma hora de duração complementada por um folheto recordatório. Serão ainda realizados dois sub-estudos, em que o V1.0, Final 28Set09 viii Sub-notificação de RAMs em Portugal – Um problema com solução ? primeiro tentará caracterizar o efeito de contaminação entre Profissionais de Saúde e o segundo pretende caracterizar a duração do efeito das intervenções educacionais. Resultados a atingir: Pretende-se, com a implementação deste projecto, aumentar o número de notificações de RAMs pelos médicos, farmacêuticos e enfermeiros em cerca de 110%, de modo a atingir-se uma taxa de notificação de aproximadamente 300 notificações por milhão de habitantes por ano (i.e., multiplicar por 2,1 o número notificações existentes). -------------------ABSTRACT - Introduction: The Adverse Drug Reactions (ADRs) are a serious Public Health problem in terms of mortality and morbidity caused, being also an economic burden for the health systems. The Spontaneous Adverse Event Reporting Systems are considered as the most effective drug surveillance methods, in which the ADR under-reporting represents one of its biggest limitations. It was estimated that only 6% of all adverse reactions are notified globally. When comparing with high ADR reporting rate countries Portugal shows a low ADR reporting rate. This study aims to: 1) characterize the physicians, pharmacists and nurses attitudes and behaviours related to ADR under-reporting; 2) characterize the educational interventions effectiveness to decrease the ADRs under-reporting. Methods: During a first phase a case-control study will be conducted in physicians, pharmacists and nurses in Continental Portugal working in the National Health System (NHS) in order to characterize their attitudes and behaviours related to ADR reporting. The Healthcare Professionals that have reported at least one ADR during a determined period will be considered as the cases and those that have not reported any ADR during the same period will be considered as the controls. The controls will be randomly selected. The study will be conducted through a self-administered questionnaire in which the questions related to the attitudes and behaviours are based in the Inmans’s “seven mortal sins”. A Visual Analogue Scale will be used to record the responses. The responses can range from 0 (totally disagree) to 10 (totally agree). Logistic regression will be used to determine the ADR reporting adjusted odds ratio (ORadj) for a change in the exposure corresponding to the interquartile range for each attitude. In the second phase of the study a cluster-randomized controlled trial will be conducted to characterize the educational interventions effectiveness focused on the first phase identified causes with the aim to decrease the ADRs under-reporting. Based in 2007’s information 43 clusters have been identified throughout the several Health Regions. The educational interventions are composed of one hour presentation complemented by an informational leaflet. Two sub-studies will be also conducted in which the first one will try to characterize the contamination effect between the Healthcare Professionals and the second to characterize the educational interventions effect duration. V1.0, Final 28Set09 x Sub-notificação de RAMs em Portugal – Um problema com solução ? Outcome: With the project implementation an increase of the ADR notifications performed by the physicians, pharmacists and nurses by 110% is aimed in order to obtain approximately 300 notifications per million habitants per year (i.e., multiply by 2,1 the existent notifications).

Accumulation, responses and genotoxicity of trace elements in octopus vulgaris

Dissertação apresentada para obtenção do Grau de Doutor em Bioquímica pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Responses of higher plants to boron deficiency

Dissertation presented to obtain the degree of Doctorate in Biochemistry by Instituto de Tecnologia Química e Biológica of Universidade Nova de Lisboa

Integration of sediment contamination with multi–biomarker responses in a novel bioindicator candidate (Sepia officinalis) for risk assessment in impacted estuaries

Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente

MicroRNAs as modulators of water deficit responses in Medicago truncatula

Dissertação para a obtenção do grau de doutor em Biologia pelo Instituto de Tecnologia Química e Biológica. Universidade Nova de Lisboa

Promoting healthy eating standards on children through CSR educational programs: An evaluation of impact on eating preferences, attitude towards the brand and perceived brand reputation

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Sustainability and consumer responses: The effect of bad industry reputation and fit

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Marketing plan for Educational Center "The Unknow Islands" Russia

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Marine toxins in bivalves: accumulation, kinetics and subcellular responses

Sociedade Polis Litoral Ria Formosa,Projects Quasus and Project Toxigest financed by PROMAR (2007-2013)

Mobile image processing to support educational geometry games

The mobile IT era is here, it is still growing and expanding at a steady rate and, most of all, it is entertaining. Mobile devices are used for entertainment, whether social through the so-called social networks, or private through web browsing, video watching or gaming. Youngsters make heavy use of these devices, and even small children show impressive adaptability and skill. However not much attention is directed towards education, especially in the case of young children. Too much time is usually spent in games which only purpose is to keep children entertained, time that could be put to better use such as developing elementary geometric notions. Taking advantage of this pocket computer scenario, it is proposed an application geared towards small children in the 6 – 9 age group that allows them to consolidate knowledge regarding geometric shapes, forming a stepping stone that leads to some fundamental mathematical knowledge to be exercised later on. To achieve this goal, the application will detect simple geometric shapes like squares, circles and triangles using the device’s camera. The novelty of this application will be a core real-time detection system designed and developed from the ground up for mobile devices, taking into account their characteristic limitations such as reduced processing power, memory and battery. User feedback was be gathered, aggregated and studied to assess the educational factor of the application.

Understanding how dentritic cell glycans affect antitumor immune responses

RESUMO: As células dendríticas (DCs) têm a capacidade única de induzir respostas imunitárias contra as células tumorais, fagocitando antigénios tumorais e apresentando-os às células T, provocando respostas imunitárias específicas que conduzem à eliminação de células de tumorais. Por induzirem memória imunológica de longa duração, as DCs são uma estratégia atrativa para o tratamento e/ou prevenção do cancro. No entanto, os resultados terapêuticos obtidos em ensaios clínicos com DCs são escassos e pouco eficientes. O nosso grupo demonstrou que ácidos siálicos que contêm glicanos desempenham um papel funcional importante em DCs geradas ex vivo. Com o objetivo de estabelecer um modelo in vitro para avaliar a resposta anti-tumoral específica realizou-se um tratamento enzimático a DCs derivadas de monócitos (moDCs) com sialidase, enzima que cliva ácidos siálicos na superfície celular. O perfil de maturação de moDCs foi caracterizado por citometria de fluxo e expressão de citocinas. Os resultados mostram que a sialidase pode regular positivamente a expressão de moléculas co-estimuladoras na superfície de moDCs estimuladas com agonistas de Toll like receptors (TLRs). Para percebermos se o tratamento com sialidase afeta a sinalização dos TLRs foram usadas células HEK transfectadas de forma estável com TLRs 2, 4 and 7/8. Os dados mostraram que a desialilação não afeta a sinalização através estes recetores. Para investigar o impacto funcional da sialidase na capacidade de moDCs em apresentar um antigénio e ativar células T, moDCs foram tratadas, ou não, com sialidase e cultivadas com clones de células T CD8+ específicas para os péptidos derivados do antigénio tumoral gp100. Os resultados mostram que DCs HLA*02:01+ desialiladas exibem maior cross-presentation do péptido gp100280-288 às células T CD8+ específicas. Além disso o tratamento com sialidase também aumenta a capacidade de DCs de induzir a proliferação de células T CD4+. Em conjunto, os resultados indicam que moDCs com menos ácidos siálicos na superfície, têm melhor potencial imuno-estimulador, com maior capacidade de induzir respostas imunes anti-tumorais.--------------------- ABSTRACT: Dendritic cells (DCs) have a unique capacity to induce immune responses against tumor cells. They can phagocyte tumor antigens, maturate and present them to T cells, triggering antigen-specific immune responses that may lead to the elimination of tumor cells. Since they induce long-lasting immunological memory, DCs become an attractive strategy as cellular targets for vaccines in the treatment and/or prevention of cancer. However, the therapeutic results obtained in clinical trials with DCs are scarce and only few patients effectively respond to the DC vaccines. Our group has shown that sialic acid containing glycans play an important functional role in ex vivo generated DC. Here we aimed to establish an in vitro model to assess specific antitumor responses. To achieve this, an enzymatic treatment of monocyte-derived DCs (moDCs) was performed using sialidase to cleave surface sialic acids. The maturation profile of the moDCs was characterized by flow cytometry and cytokine expression. The results show that sialidase treatment can upregulate co-stimulatory molecules on surface of moDCs stimulated with Toll like receptor (TLR) agonists. To understand whether sialidase treatment affected the TLR signaling, we have used HEK cells stably transfected with TLRs 2, 4 and 7/8. The data showed that desialylation of moDCs does not affect the signaling via these receptors. To investigate the functional impact of sialidase treatment in the capacity of moDCs to present antigen and to activate antigen specific T cells, sialidase treated and untreated moDCs were co-cultured with CD8+ T cell clones specific for peptides derived from the gp100 tumor antigen. Our results show that desialylated HLA02:01+ DCs are superior in cross-presentation of the peptide to gp100280–288 specific CD8+ T cells. In addition, sialidase treatment also increased the DC capacity to induce CD4+ T cells proliferation. Together, these data indicate that moDCs with altered cell surface sialic acids, through a sialidase treatment, have a better immunostimulatory potential which could improve anti-tumor immune responses.

exploring the differences of CSR and CSE activities on consumer attributions and responses

The following directed research project analyzes how different sustainability efforts of an organization influence consumers’ responses in an industry, which faces high controversy. The study tested shows how two different high fit sustainability endeavors, namely high fit Corporate Social Responsibility (CSR) activities and Corporate Social Entrepreneurship (CSE), affect the way consumers’ attributions are being made with regard to the company’s motive. With data gathered from surveying 156 participants, the study provides evidence that CSR as well as CSE programs stimulate values-driven attributions which positively affect consumers’ trust, corporate reputation and corporate image. Lastly, theoretical and managerial implications of the study are discussed and future research suggestions provided.