Impact of the economic crisis in the approval of new oncological drugs:the Portuguese paradigm

Background: The European crisis lead to funding restrains in healthcare, already under pressure due to the ageing of the population and the increase of demands from innovation. Portugal is the paradigm of the European crisis since has both an economic and demographic crisis. The researchers aimed to evaluate the impact of economic restrains in Portugal for access and reimbursement of new oncological drugs. Methodology: A qualitative approach was used, supported by 27 formal, tape recorded, semi-structured interviews to representatives of the different healthcare stakeholders and policymakers. The content analysis with semantic associations through co-occurrence analysis were done with the support of Tropes® software. Results: The results of the content analysis showed that economic restrains are leading to a policy of cost control with lower prices and reduced access to innovation; an excessive delay in the approval of new drugs; lack of transparency; serious limitations and inequity between hospitals. Contractual boundaries to national prescription was established and agreements with pharmaceuticals were made. Changes in the reimbursement process are being implemented with an increase of risk sharing mechanisms and implementation of a new system of health technological evaluation (SINATS). Treatment protocols are also being revised and public hospitals are trying to increase the number of clinical trials but there is still much bureaucracy. In this qualitative approach, the following factors with impact on survival were identified: Innovation and technological development, government funding, the price of drugs and type of oncological diseases. Conclusions: The economic crisis is leading to a very serious problem of inequity. However, it is also an opportunity for a structural reform. In Portugal, an attempt of reform is being made with the implementation of SINATS since it is important to distinguish molecules that effectively bring added value. In order to consider the strategic vision in which the patient is the center of all efforts, the process of reimbursement approval for new medicines should be faster, more transparent and interdisciplinary. Moreover, the decisions must be done triangulating evidence based medicine, economics, health policy and ethical and legal issues. For National Health Service sustainability, efficiency and efficacy, clinical and economic reassessments must be done after market introduction of new medicines, with subsequent renegotiations.info:eu-repo/semantics/publishedVersio

Metabolic network reconstruction of the central carbon metabolism of Enterococcus faecalis

The profound advance in experimental high throughput techniques (generally referred to as “omics techniques”) has enabled the analysis of a large number of components within a living cell. The vast amount of data obtained from the different “omics” (genomics, proteomics, fluxomics, metabolomics, transcriptomics) demands the use of bioinformatics tools. These methods comprise the development of comparative tools and maintenance of databases for the analysis of genomics data, in addition to the construction of models for the analysis and integration of data in a system-wide approach. Enterococcus faecalis is a Gram-positive bacterium that is getting more attention due to its “two-face” behavior. This natural inhabitant of the mammalian gastrointestinal tract is also an opportunist pathogen responsible for urinary tract infections, nosocomial infections, bacteremia and infective endocarditis. Besides, its intrinsic physiological properties such as inherent antibiotic resistance and exceptional ability to adapt to harsh conditions provide this organism with an enormous advantage in the infection processes. Here, we propose to reconstruct the genome scale metabolic network of the central carbon metabolism of Enterococcus faecalis using genome sequencing information available on different databases as well as proteomics and metabolomics data. The first metabolic model generated for this bacterium will allow correlating metabolite levels and fluxes which enables identification of key control points in its metabolism. As it has been previously shown for other organisms, the metabolic network reconstruction may serve as a valuable tool to predict the phenotypic behaviour under various genetic and environmental conditions

Genome scale metabolic network reconstruction of pathogen – Enterococcus faecalis

Enterococcus faecalis is a Gram-positive bacterium that is getting more attention due to its “two-face” behavior. This natural inhabitant of the gastrointestinal mammalian tract is also an opportunist pathogen responsible for urinary tract infections, nosocomial infections, bacteremia and infective endocarditis (1). Since the metabolic reconstruction of Haemophilus influenzae was published in 1999 (2), many other researchers have focused their attention into the possibilities that the new era of genome-scale metabolic models could bring to the scientific scene, both in prokaryotic and eukaryotic organisms

Genome-scale metabolic network of the central carbon metabolism of Enterococcus faecalis

The profound advance in experimental high throughput techniques (generally referred to as omics techniques) has enabled the analysis of a large number of components within a living cell. The vast amount of data obtained from the different omics (genomics, proteomics, fluxomics, metabolomics, transcriptomics) demands the use of bioinformatics tools. These methods comprise the development of comparative tools and maintenance of databases for the analysis of genomics data, in addition to the construction of models for the analysis and integration of data in a system-wide approach. Enterococcus faecalis is a gram-positive bacterium that is getting more attention due to its two-face behavior. This natural inhabitant of the mammalian gastrointestinal tract is also an opportunist pathogen responsible for urinary tract infections, nosocomial infections, bacteremia and infective endocarditis. Besides, its intrinsic physiological properties such as inherent antibiotic resistance and exceptional ability to adapt to harsh conditions provide this organism with an enormous advantage in the infection processes. Here, we propose to reconstruct the genome scale metabolic network of the central carbon metabolism of Enterococcus faecalis using genome sequencing information available on different databases as well as proteomics and metabolomics data. The first metabolic model generated for this bacterium will allow correlating metabolite levels and fluxes which enables identification of key control points in its metabolism. As it has been previously shown for other organisms, the metabolic network reconstruction may serve as a valuable tool to predict the phenotypic behaviour under various genetic and environmental conditions.Supported by a PhD grant from the FCT (Portuguese Science Foundation): SFRH/BD/47016/2008 and funding from HRC (Health Research Council of New Zealand)

Extranodal non-Hodgkin´s lymphomas: a retrospective study

Na maioria dos linfomas não-Hodgkin (LNH), o envolvimento extra-ganglionar surge durante o curso da doença. Contudo alguns LNH têm origem em locais que não os gânglios linfáticos ou o baço, sendo designados por LNH extra-ganglionares. Este estudo tem como objectivo ilustrar as características clínico-patológicas dos doentes com LNH extra-ganglionares primários (LNH-EP). Foram avaliados 125 casos de LNH, dos quais 37 (30%) foram considerados LNH-EP. A proporção entre os sexos foi de 1:1, com uma média de idades de 61 anos. Surgiram 8 casos (20%) de LNH de fenótipo T e 29 casos (80%) de LNH de fenótipo B. Os locais mais atingidos foram a pele em 12 casos (32,4%) e o trato gastrointestinal em 11 (29,7%); 24% tinham sintomas B; 81% eram localizados (estadio IE e IIE). De acordo com a histologia, segundo a classificação da OMS, 1 caso (3%) era altamente agressivo (linfoma de Burkitt), 68% agressivos e 29% indolentes. O linfoma B difuso de grandes células (LNH B DGC) constitui 51% e o linfoma de MALT 14% de todos os casos. O índice de prognóstico internacional (IPI) demonstrou que 7% dos doentes pertenciam ao grupo de risco alto, 3% intermédio alto, 20% risco intermédio baixo e 70% risco baixo. Em conclusão, os LNH-EP são um grupo heterogéneo de doenças, sendo as localizações mais frequentes a pele e o trato gastrointestinal. Há uma maior percentagem de LNH T extra-ganglionar do que o descrito para o LNH ganglionar. O tipo histológico mais frequente foi o LNH B DGC. O IPI revelou-se discriminativo relativamente à sobrevivência, mas a sua aplicabilidade nos LNH extra-ganglionares é questionável, porque não divide homogeneamente os doentes. (Discussão) (...) A classificação hematológica das neoplasias para a OMS divide as neoplasias em células B, células T e células 'natural killer'. A importância desta classificação histológica reside no comportamento clínico (indolente, agressivo, muito agressivo) do LNH em questão. Os LNH indolentes (centro-folicular, zona marginal incluíndo MALT, micose fungóide) têm sobrevivência longa mesmo sem tratamento; os LNH agressivos e muito agressivos têm cura mas são rapidamente fatais se não forem tratados ou se se revelarem resistentes. No nosso estudo não foi possível estabelecer uma relação entre sobrevivência aos 12 meses nos LNH indolentes comos agressivos. No grupo dos LNH muito agressivos (l. Burkitt) só existiu 1 caso, que permaneceu vivo e sem doença até ao fim do estudo. Os que tinham doença localizada tiveram sobrevivência maior do que os que tinham doença disseminada, não sendo possível contudo estabelecer uma correlação estatisticamente significativa. Este achado parece-nos relevante, e pode não ser inteiramente inesperado: o sistema de estadiamento de Ann Arbor foi criado para a estratificação de doentes com linfoma de Hodgkin, que ao contrário dos LNH evolui e progride por patamares sequenciais, atingindo as cadeias ganglionares a partir de um gânglio patológico. Quanto à biologia do LNH, o processo é diferente, podendo haver doença extra-ganglionar ou atingimento da medula óssea apesar de escassa massa tumoral ganglionar, o que traduz uma insuficiente correlação entre a massa tumoral e o patamar de evolução, mensurado pelo sistema de Ann Arbor no caso de LNH. A incapacidade discriminativa deste sistema para medir a massa tumoral e o prognóstico levou ao aparecimento do IPI (índice prognóstico internacional), especificamente adaptado ao LNH de alto grau. Posteriormente surgiram o FLIPI e MIPI adaptados do linfoma folicular e de células do manto, respectivamente. Neste trabalho confirmou-se que o sistema de Ann Arbor não é útil para os LNH extra-ganglionares. Demonstrou-se que existe uma correlação estatisticamente significativa nos doentes com DHL elevada e IPI de alto grau, associando-se uma maior mortalidade. A utilidade clínica do IPI no LNH extra-ganglionar levanta no entanto alguma dificuldade, já que estratifica mal os doentes; a maioria pertencia ao grupo de baixo risco e só 10% estavam no grupo de alto risco, onde se pode prever uma evolução mais agressiva. Uma vez que o nosso estudo é retrospectivo e tem uma amostra reduzida, as conclusões devem ser tomadas com precaução. Será necessário um aumento da amostra em estudo e/ou a conjugação com dados de outros centros para se estabelecerem premissas com maior poder estatístico. (Conclusão) Os linfomas cutâneos e do trato gastrointestinal demonstraram ser os mais prevalentes, assim como o subtipo histológico de LNH difuso de grandes células. O IPI demonstrou ser um factor discriminatório na sobrevida dos doentes, mas não estratifica os doentes por grupos homogéneos, e portanto é de utilização duvidosa nos LNH extra-ganglionares