Monitorização e reporte ao sistema de farmacovigilância europeu da nova terapêutica para a Hepatite C (Harvoni®)

A Hepatite C é uma doença hepática provocada por um vírus, designado de vírus da Hepatite C. Após a entrada do vírus no organismo, desenvolve-se a fase aguda da infeção. Após seis meses de início da infeção, esta evolui de aguda para crónica. Numa fase crónica, o ácido ribonucleico do vírus persiste no sangue, podendo a longo prazo originar cirrose hepática, carcinoma hepatocelular e falha hepática. A Hepatite C é uma doença para a qual ainda não foi desenvolvida uma vacina, sendo por isso o tratamento a única alternativa para os doentes. O tratamento tem vindo a sofrer ao longo dos anos uma enorme evolução. As primeiras terapias eram injetáveis, de longa duração, com efeitos adversos graves e com baixas taxas de sucesso. Em contrapartida, as mais recentes terapias são orais, de menor duração e com taxas de sucesso promissoras associadas à ocorrência de efeitos adversos menos graves. Em 2014, foi aprovado o Harvoni®, uma junção de sofosbuvir com ledipasvir, administrados numa única toma diária, variando entre 8, 12 e 24 semanas o tratamento, de acordo com a tipologia do doente. Na elaboração bibliográfica desta dissertação realizaram-se diversas pesquisas em várias bases de dados de cariz científico. Esta dissertação tem, como principal objetivo analisar os efeitos adversos do Harvoni® reportados à Agência Europeia do Medicamento. Cada efeito adverso reportado, é analisado quanto à tipologia do reportador e ao sexo, idade e origem geográfica do doente. Posteriormente, cada efeito adverso é inserido num grupo patológico. Com base neste reporte, verificou-se que existem diversos efeitos adversos graves, como por exemplo, mortes, tendências suicidas, falha e ineficácia do tratamento, encefalopatia, acidente vascular cerebral, enfarte do miocárdio e insuficiência cardíaca e hepática. No entanto, com base nos ensaios clínicos prévios à introdução do Harvoni® no mercado, os efeitos adversos são comuns, não representando perigo para o doente, nem um risco para a interrupção do tratamento. Sendo assim, é necessário ponderar o risco/benefício incutido no uso do Harvoni®, para cada doente com Hepatite C crónica.Hepatitis C is a disease caused by a virus, designated Hepatitis C virus. After the entry of the virus in the organism, the acute phase of the infection develops. Six months after the beginning of the infection, it evolves from acute to chronic. At a chronic phase, the virus ribonucleic acid stays in the blood, which can lead to long-term liver cirrhosis, hepatocellular carcinoma and liver failure. Hepatitis C is a disease which a vaccine hasn’t yet been developed, so treatment is the only alternative for the patient. The treatment has been under tremendous evolution over the years. The first therapies were injectable, long-lasting, with severe adverse effects and low success rates. On the other hand, newer oral therapies are of shorter duration and with promising success rates associated with the occurrence of less severe side effects. In 2014, Harvoni®, a combination of sofosbuvir with ledipasvir, was approved, to be administrated in a single daily dose, ranging from 8, 12 and 24 weeks of treatment, according to the patient type. The bibliographic research of this dissertation was carried out with several researches in various scientific-oriented databases. This work has as main purpose to analyze the adverse effects of Harvoni® reported to the European Medicine Agency. Each reported adverse effect is analyzed for the type of the person that made the report, as well as the gender, age and geographic origin of the patient. Subsequently, each adverse effect is inserted in a pathologic group. Based on this report, it was found that there are several serious adverse effects such as death, suicidal tendencies, and ineffectiveness and treatment failure, encephalopathy, stroke, myocardial infarction and cardiac and hepatic insufficiency. However, based on clinical trials of Harvoni® previous to the introduction in the market, side effects are common and represent no danger to the patient or a threat to discontinuation of treatment. Therefore, it is necessary to weigh the risk / benefit instilled in the use of Harvoni® in each patient with chronic Hepatitis C

Práticas de responsabilidade social no sector público: o caso das empresas locais em Portugal

In today’s business world, social responsibility is crucial because many societal issues stem from companies’ actions. Therefore, it is essential to have socially responsible companies that support sustainable development principles and strive to create a fairer and more equitable society in economic, social, and environmental aspects. To ensure transparency, companies should share both positive and negative impacts achieved through sustainable practices in a sustainability report for their stakeholders. This paper analyzes the sustainability reports of public-local companies in Portugal using the Global Reporting Initiative (GRI) indicators to evaluate their social responsibility practices. The analysis combines qualitative and quantitative data from the reports disclosed on the local public company’s website. Unfortunately, it was found that social responsibility practices still need to be standard in these companies. Only a few companies publish sustainability reports, which are still in their early stages. The economic dimension is the most widely reported as it is easier to quantify and collect data.No mundo empresarial de hoje, a responsabilidade social é crucial porque muitos problemas sociais resultam das ações das empresas. Por conseguinte, é essencial ter empresas socialmente responsáveis que apoiem os princípios do desenvolvimento sustentável e se esforcem por criar uma sociedade mais justa e equitativa nos aspetos económicos, sociais e ambientais. Para garantir a transparência, as empresas devem partilhar os impactos positivos e negativos alcançados através de práticas sustentáveis num relatório de sustentabilidade para as suas partes interessadas. Este artigo analisa os relatórios de sustentabilidade das empresas locais em Portugal, utilizando os indicadores da Global Reporting Initiative (GRI) para avaliar as suas práticas de responsabilidade social. A análise feita combina dados qualitativos e quantitativos dos relatórios divulgados no sítio web da empresa local. Infelizmente, verificou-se que as práticas de responsabilidade social ainda precisam de ser normalizadas nestas empresas. Apenas algumas empresas publicam os relatórios de sustentabilidade, que estão ainda numa fase inicial. A dimensão económica é a mais divulgada, uma vez que é a mais fácil de quantificar e de recolher dados.info:eu-repo/semantics/publishedVersio

Antimicrobial and antiproliferative potential of Anadenanthera colubrina (vell.) Brenan

The aim of the present study was to perform an in vitro analysis of the antimicrobial and antiproliferative potential of an extract from Anadenanthera colubrina (Vell.) Brenan (angico) and chemically characterize the crude extract. Antimicrobial action was evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration, and the inhibition of formation to oral biofilm. Cell morphology was determined through scanning electron microscopy (SEM). Six strains of tumor cells were used for the determination of antiproliferative potential. The extract demonstrated strong antifungal activity against Candida albicans ATCC 18804 (MIC = 0.031 mg/mL), with similar activity found regarding the ethyl acetate fraction. The extract and active fraction also demonstrated the capacity to inhibit the formation of Candida albicans to oral biofilm after 48 hours, with median values equal to or greater than the control group, but the difference did not achieve statistical significance (P > 0.05). SEM revealed alterations in the cell morphology of the yeast. Regarding antiproliferative activity, the extract demonstrated cytostatic potential in all strains tested. The present findings suggest strong antifungal potential for Anadenanthera colubrina (Vell.) Brenan as well as a tendency toward diminishing the growth of human tumor cells.The aim of the present study was to perform an in vitro analysis of the antimicrobial and antiproliferative potential of an extract from Anadenanthera colubrina (Vell.) Brenan (angico) and chemically characterize the crude extract. Antimicrobial action was evaluated based on the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration, and the inhibition of formation to oral biofilm. Cell morphology was determined through scanning electron microscopy (SEM). Six strains of tumor cells were used for the determination of antiproliferative potential. The extract demonstrated strong antifungal activity against Candida albicans ATCC 18804 ( mg/mL), with similar activity found regarding the ethyl acetate fraction. The extract and active fraction also demonstrated the capacity to inhibit the formation of Candida albicans to oral biofilm after 48 hours, with median values equal to or greater than the control group, but the difference did not achieve statistical significance . SEM revealed alterations in the cell morphology of the yeast. Regarding antiproliferative activity, the extract demonstrated cytostatic potential in all strains tested. The present findings suggest strong antifungal potential for Anadenanthera colubrina (Vell.) Brenan as well as a tendency toward diminishing the growth of human tumor cells201

Identification of clusters of asthma control: A preliminary analysis of the inspirers studies

This work was funded by ERDF (European Regional Development Fund) through the operations: POCI- -01-0145-FEDER-029130 (“mINSPIRERS—mHealth to measure and improve adherence to medication in chronic obstructive respiratory diseases - generalisation and evaluation of gamification, peer support and advanced image processing technologies”) co-funded by the COMPETE2020 (Programa Operacional Competitividade e Internacionalização), Portugal 2020 and by Portuguese Funds through FCT (Fundação para a Ciência e a Tecnologia).© 2020, Sociedade Portuguesa de Alergologia e Imunologia Clinica. All rights reserved. Aims: To identify distinct asthma control clusters based on Control of Allergic Rhinitis and Asthma Test (CARAT) and to compare patients’ characteristics among these clusters. Methods: Adults and adolescents (≥13 years) with persistent asthma were recruited at 29 Portuguese hospital outpatient clinics, in the context of two observational studies of the INSPIRERS project. Demographic and clinical characteristics, adherence to inhaled medication, beliefs about inhaled medication, anxiety and depression, quality of life, and asthma control (CARAT, >24 good control) were collected. Hierarchical cluster analysis was performed using CARAT total score (CARAT-T). Results: 410 patients (68% adults), with a median (percentile 25–percentile 75) age of 28 (16-46) years, were analysed. Three clusters were identified [mean CARAT-T (min-max)]: cluster 1 [27(24-30)], cluster 2 [19(14-23)] and cluster 3 [10(2-13)]. Patients in cluster 1 (34%) were characterised by better asthma control, better quality of life, higher inhaler adherence and use of a single inhaler. Patients in clusters 2 (50%) and 3 (16%) had uncontrolled asthma, lower inhaler adherence, more symptoms of anxiety and depression and more than half had at least one exacerbation in the previous year. Further-more, patients in cluster 3 were predominantly female, had more unscheduled medical visits and more anxiety symp-toms, perceived a higher necessity of their prescribed inhalers but also higher levels of concern about taking these inhalers. There were no differences in age, body mass index, lung function, smoking status, hospital admissions or specialist physician follow-up time among the three clusters. Conclusion: An unsupervised method based on CARAT--T, identified 3 clusters of patients with distinct, clinically meaningful characteristics. The cluster with better asthma control had a cut-off similar to the established in the validation study of CARAT and an additional cut-off seems to distinguish more severe disease. Further research is necessary to validate the asthma control clusters identified.publishersversionpublishe

Cuidados biomédicos de saúde em Angola e na Companhia de Diamantes de Angola, c. 1910-1970

Pretende-se caracterizar a prestação de cuidados biomédicos em Angola durante a atividade da Companhia de Diamantes de Angola. Uma análise comparativa de políticas e práticas de saúde pública de vários atores coloniais, como os serviços de saúde da Companhia, sua congénere do Estado e outras empresas coloniais, revelará diferenças de investimento na saúde, isto é, instalações e pessoal de saúde, e tratamentos. Este escrutínio bem como as condições de vida iluminarão o carácter idiossincrático e central dos serviços de saúde da Companhia em termos de morbimortalidade em Angola, e a centralidade destes para as representações de um império cuidador

Práticas de responsabilidade social no setor público – o caso das empresas locais

Objetivos: Os objetivos gerais deste trabalho são (i) identificar as principais práticas de responsabilidade social nas empresas locais; e (ii) analisar o contributo destas práticas para a reputação destas empresas e para o desenvolvimento sustentável. Metodologia / Abordagem: Para dar resposta aos objetivos propostos, procedeu-se ao levantamento sucinto da temática, nomeadamente a evolução do conceito de responsabilidade social e o seu contributo para a reputação das empresas, bem como a satisfação tanto dos públicos internos como externos (fornecedores, clientes, autoridades públicas, consumidores e sociedade local). Procedeu-se, também, ao levantamento de estudos realizados a nível internacional e nacional, sobre a adoção de práticas de responsabilidade social, em particular, pelo setor público. Neste caso concreto, atenderemos ao conceito de empresas locais presentes no artigo 19.º, da Lei n.º 50/2012, de 31 de agosto. Na componente empírica, fez-se o levantamento das empresas locais existentes em Portugal (segundo dados publicados no Portugal Autárquico contabiliza-se 184 empresas locais) e dos relatórios de sustentabilidade publicados por estas empresas, nomeadamente nos seus sítios da internet e com recurso à análise mista (qualitativa e quantitativa), analisou-se os relatórios recolhidos com vista a identificar as práticas de responsabilidade social adotadas, tendo como referencial as normas do Global Reporting Iniciative (GRI). Conclusões / Resultados: Os principais resultados desta investigação serão úteis, para verificar as práticas de responsabilidade social adotadas pelas empresas locais, sendo expetável que esta matéria não esteja ainda devidamente integrada na gestão dessas empresas. Tendo como referência o que é corrente nas empresas do setor privado, espera-se que as práticas mais comumente adotadas pelas empresas do setor público sejam as relacionadas com as questões ambientais, as ligadas à comunidade e aos seus stakeholders internos.info:eu-repo/semantics/publishedVersio

Intranasal delivery of nanostructured lipid carriers, solid lipid nanoparticles and nanoemulsions: a current overview of in vivo studies

The management of the central nervous system (CNS) disorders is challenging, due to the need of drugs to cross the blood‒brain barrier (BBB) and reach the brain. Among the various strategies that have been studied to circumvent this challenge, the use of the intranasal route to transport drugs from the nose directly to the brain has been showing promising results. In addition, the encapsulation of the drugs in lipid-based nanocarriers, such as solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) or nanoemulsions (NEs), can improve nose-to-brain transport by increasing the bioavailability and site-specific delivery. This review provides the state-of-the-art of in vivo studies with lipid-based nanocarriers (SLNs, NLCs and NEs) for nose-to-brain delivery. Based on the literature available from the past two years, we present an insight into the different mechanisms that drugs can follow to reach the brain after intranasal administration. The results of pharmacokinetic and pharmacodynamics studies are reported and a critical analysis of the differences between the anatomy of the nasal cavity of the different animal species used in in vivo studies is carried out. Although the exact mechanism of drug transport from the nose to the brain is not fully understood and its effectiveness in humans is unclear, it appears that the intranasal route together with the use of NLCs, SLNs or NEs is advantageous for targeting drugs to the brain. These systems have been shown to be more effective for nose-to-brain delivery than other routes or formulations with non-encapsulated drugs, so they are expected to be approved by regulatory authorities in the coming years.info:eu-repo/semantics/publishedVersio

Using the quality by design (QbD) approach to optimize formulations of lipid nanoparticles and nanoemulsions: a review

Quality-by-design (QbD) approach has been applied to optimize lipid-based nanosystems formulations, including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions, besides being increasingly requested by regulatory authorities. Different mathematical models and statistical tests have been used, with similar conclusions regarding the parameters that influence the physical features of the resulting nanosystems. These include, variations in composition (e.g. lipid(s) and/or emulsifier(s)) and manufacturing parameters (e.g. emulsification rate and/or time, sonication amplitude and/or time, and homogenization pressure and/or cycles). These are critical parameters that influence nanoparticle/globule mean size, polydispersity index, zeta potential, drug encapsulation efficiency and in vitro drug release. This review addresses the concepts and applications of QbD for the development of lipid-based nanosystems, reporting successful examples published in the last 2 years. Although, some limitations have been identified, it is expected that in the upcoming years the application of QbD in pharmaceutical development will be an established approach.info:eu-repo/semantics/publishedVersio

Application of the Quality-by-Design (QbD) approach to improve the nose-to-brain delivery of diazepam-loaded Nanostructured Lipid Carriers (NLCs)

The intranasal administration of nanostructured lipid carriers (NLCs) has been suggested as a promising strategy to improve the fast treatment of epilepsy. This route allows for drug passage directly from the nose to the brain, avoiding the need of bypassing the blood–brain barrier. In addition, the quality-by-design (QbD) approach is a useful tool for the optimization of manufacturing variables, resulting in effective and safe pharmaceutical formulations. The aim of this work was to use the QbD approach to optimize a NLCs formulation for the nose-to-brain delivery of diazepam. The studies began with the screening of excipients and the assessment of the lipid-drug compatibility. The central composite design was used to evaluate the effects of critical material attributes (CMAs) (ratio of solid and liquid lipids and the amount of drug and emulsifiers) on the CQAs of the diazepam-loaded NLCs formulation (particle size, polydispersity index (PDI), zeta potential (ZP) and encapsulation efficiency (EE)). The results showed that the most adequate ratios of lipids and emulsifiers were 6.65:2.85 and 4.2:0.3 (%, w/w), with values of 84.92 nm, 0.18, −18.20 mV and 95.48% for particle size, PDI, ZP and EE, respectively. This formulation was selected for further studies related to the optimization of critical process parameters (CPPs).info:eu-repo/semantics/publishedVersio

In Vitro Studies on Nasal Formulations of Nanostructured Lipid Carriers (NLC) and Solid Lipid Nanoparticles (SLN)

The nasal route has been used for many years for the local treatment of nasal diseases. More recently, this route has been gaining momentum, due to the possibility of targeting the central nervous system (CNS) from the nasal cavity, avoiding the blood−brain barrier (BBB). In this area, the use of lipid nanoparticles, such as nanostructured lipid carriers (NLC) and solid lipid nanoparticles (SLN), in nasal formulations has shown promising outcomes on a wide array of indications such as brain diseases, including epilepsy, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease and gliomas. Herein, the state of the art of the most recent literature available on in vitro studies with nasal formulations of lipid nanoparticles is discussed. Specific in vitro cell culture models are needed to assess the cytotoxicity of nasal formulations and to explore the underlying mechanism(s) of drug transport and absorption across the nasal mucosa. In addition, different studies with 3D nasal casts are reported, showing their ability to predict the drug deposition in the nasal cavity and evaluating the factors that interfere in this process, such as nasal cavity area, type of administration device and angle of application, inspiratory flow, presence of mucoadhesive agents, among others. Notwithstanding, they do not preclude the use of confirmatory in vivo studies, a significant impact on the 3R (replacement, reduction and refinement) principle within the scope of animal experiments is expected. The use of 3D nasal casts to test nasal formulations of lipid nanoparticles is still totally unexplored, to the authors best knowledge, thus constituting a wide open field of research