Post authorisation effetiveness studies- aspetos legais e regulamentares, relevância, estrutura e metodologia

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2021, Universidade de Lisboa, Faculdade de Farmácia.A evolução da farmacoepidemiologia a par com a evolução tecnológica impulsionou a introdução, o desenvolvimento e a utilização de ferramentas inovadoras que permitem avaliar a relação benefício-risco, a segurança e as especificidades das terapêuticas quer em processo de aprovação quer já introduzidas no mercado. O processo de introdução de um medicamento no mercado caracteriza-se por ser muitas vezes complexo, detalhado e restritivo, dada toda a legislação e requerimentos associados ao contexto epidemiológico, clínico e farmacológico de cada sistema de avaliação e aprovação de medicamentos. A autorização de introdução de um medicamento no mercado, é um processo regulado pelas autoridades competentes, que apesar de cada vez mais uniformizado, sistemático e transparente contem algumas limitações próprias do processo. A realização de Estudos de Pós Autorização, entre os quais os Estudos de Pós Autorização de Eficácia, é uma das ferramentas metodológicas inovadoras criada para esclarecer incertezas, avaliar as terapêuticas disponíveis e auxiliar na tomada de decisão por parte das autoridades competentes. Baseados em dados do mundo real, estes estudos apresentam-se como uma das principais formas de complementar os dados adquiridos através dos ensaios de fase I, II e III e mitigar as limitações destes ensaios. Esta monografia tem como principal objetivo descrever as diferentes metodologias, contextos legislativos dos estudos de Pós Autorização de Introdução no Mercado de Eficácia e tirar ilações sobre a relevância e impacto dos mesmos no ciclo do medicamento. Para tal utilizou-se como case study o estudo de efetividade a longo prazo da vacina Zostavax®, que permitiu demonstrar a relevância destes estudos como instrumento para esclarecer incertezas e aferir dados não disponíveis de outra forma.The evolution of pharmacoepidemiology combined with the recent technological evolution led to the introduction, development, and use of innovative tools that enable the evaluation of the risk-benefit ratio, safety, and specificities of drugs, in the process of approval or already established in the market. The process of introducing a drug onto the market is often complex, detailed, and restrictive, due to all the legislation and requirements associated with the epidemiological, clinical, and pharmacological context of each drug evaluation and approval system. The introduction of a drug onto the market is a process regulated by the competent authorities, which, despite the efforts to become more uniform, systematic, and transparent, still contains some limitations. The conduction of Post-Authorization Studies, including the Post-Authorization Studies of Effectiveness, is one of the innovative methodological tools created to clarify uncertainties, assess available therapies, and assist in decision-making by the competent authorities. Based on real-world data, these types of studies are presented as one of the main ways to complement the data acquired through the phase I, II, and III trials and to diminish the limitations identified so far. This work's main objective is to evaluate the different methodologies, legislative contexts of Post Authorization Efficacy Studies and to draw conclusions about their relevance and impact in the medicines cycle. For this purpose, the study of the long-term effectiveness of the Zostavax® vaccine was used as a case study, to shed light on the relevance of these studies as an instrument to clarify uncertainties and assess data otherwise not available

O potencial económico da internet das coisas nas empresas agrícolas do Alentejo

O trabalho desenvolvido pretende compreender o impacto do investimento em tecnologias de internet das coisas na rendibilidade de uma exploração. A metodologia baseia-se na elaboração de contas de atividade da vinha para os diferentes anos em análise e através do cálculo de outros indicadores de rendibilidade económica. Por motivos de conveniência a análise recaiu sobre a exploração Monte da Comenda e a recolha de dados foi feita através de um guião e uma folha de cálculo estruturada. Com base nos dados obtidos realizou-se o apuramento e a análise de diversos indicadores económicos. Os resultados mostram um aumento de produção e uma redução nos custos totais, melhorando a rendibilidade da exploração vitícola. A principal limitação prendeu-se à confidencialidade de alguns dados, o que limitou a análise de alguns indicadores. Apesar de não ter sido alvo deste estudo, importa salientar que há impactos da internet das coisas nas componentes ambiental e social; ABSTRACT: “The economic potential of the Internet of Things in agricultural companies in Alentejo” The work developed aims to understand the impact of investment in internet of things technologies on the profitability of an exploitation. The methodology is based on the preparation of accounts of vineyard activity for the different years under analysis and calculation of other indicators of economic profitability. For reasons of convenience, the analysis fell on the exploitation Monte da Comenda and data collection was done through a script and a structured spreadsheet. Based on the data obtained, the clearance and analysis of various economic indicators was carried out. The results show an increase in production and reduction in total costs, improving the profitability of wine-growing. The main limitation was the confidentiality of some data which limited the analysis of some indicators. Although it was not the target of this study, it is important to point out that there are impacts of the Internet of Things on environmental and social components

Comparing follow-up of patients with vitamin K antagonists in a health center: pre- and post- COVID-19 pandemic

Introduction and objectives: During the COVID-19 pandemic, the follow-up of patients treated with vitamin K antagonists (VKAs) may have been affected. This study aims to compare how these patients were monitored preand post-COVID-19 pandemic and understand the impact of non-face-to-face appointments on their follow-up. Methods: We conducted a retrospective cohort study in a Portuguese Health Center. The study included patients treated with VKAs and followed at the Health Center for international normalized ratio (INR) monitoring between March 2019 and March 2021. Data collected: sex, age, type of VKA; INR; date of INR assessment, type of appointment (face-to-face or phone/e-mail). Rosendaal’s method was used to calculate pre-COVID-19 and post-COVID-19 time in therapeutic range (TTR). Good TTR control was defined if values ≥ 70%. Results: 44 patients were included. The mean TTR in the pre-COVID-19 period was 64.55% (95% CI: 58.10 - 71.00%). The post-COVID-19 mean was slightly higher (+ 2.26%), 66.81% (95% CI: 59.66 - 73.97%), but the difference was not statistically significant (p = 0.576). The use of non-face-to-face appointments did not contribute to worsening post-pandemic TTR, showing no lower follow-up than during pre-pandemic period in which all contacts were face-to-face [CI (95%) -0.397 - 0.196 for a reference range -0.489 - 0.693]. Conclusions: The TTR value in both periods was similar and lower than the value defined for effective hypocoagulation. The use of non-face-to-face consultation in the post-COVID-19 period does not seem to have influenced the quality of hypocoagulation.Introdução e objetivos: Durante a pandemia COVID-19 o acompanhamento de doentes medicados com antagonistas da vitamina K (AVKs) pode ter sido afetado. Este estudo pretende comparar a forma como estes doentes foram monitorizados antes e depois da pandemia COVID-19 e compreender o impacto da consulta não presencialno seu seguimento. Métodos: Estudo de coorte retrospetivo num Centro de Saúde em Portugal. O estudo incluiu doentes tratados com AVKs e seguidos no Centro de Saúde para monitorização do International Normalized Ratio (INR) entre março de 2019 e março de 2021. Dados recolhidos: sexo, idade, tipo de AVK; INR; data da avaliação do INR, tipo de consulta (presencial ou por telefone/e-mail). Foi utilizado o método de interpolação linear de Rosendaal para calcular o tempo em intervalo terapêutico (TTR) pré- e pós-COVID-19. Foi definido um bom controle se valores de TTR ≥ 70%. Resultados: Foram incluídos 44 doentes. A média de TTR no período pré-COVID-19 foi de 64,55% (95% IC: 58,10 - 71,00%). A média pós-COVID-19 foi ligeiramente superior (+ 2,26%), 66,81% (95%IC: 59,66 - 73,97%), mas a diferença não foi estatisticamente significativa (p = 0,576). A utilização da consulta não presencial não contribuiu para o agravamento do TTR no período pós-pandemia, não mostrando um seguimento inferior ao do período pré-pandemia em que todos os contatos foram presenciais [IC (95%) -0,397 - 0,196 para um intervalo de referência -0,489 - 0,693]. Conclusões: O valor de TTR em ambos os períodos foi semelhante e inferior ao valor definido para hipocoagulação eficaz. A utilização da consulta não presencial no período pós-COVID-19 não parece ter influenciado a qualidade da hipocoagulação

Salivary gland extract from Aedes aegypti improves survival in murine polymicrobial sepsis through oxidative mechanisms

Sepsis is a systemic disease with life-threatening potential and is characterized by a dysregulated immune response from the host to an infection. The organic dysfunction in sepsis is associated with the production of inflammatory cascades and oxidative stress. Previous studies showed that Aedes aegypti saliva has anti-inflammatory, immunomodulatory, and antioxidant properties. Considering inflammation and the role of oxidative stress in sepsis, we investigated the effect of pretreatment with salivary gland extract (SGE) from Ae. aegypti in the induction of inflammatory and oxidative processes in a murine cecum ligation and puncture (CLP) model. Here, we evaluated animal survival for 16 days, as well as bacterial load, leukocyte migration, and oxidative parameters. We found that the SGE pretreatment improved the survival of septic mice, reduced bacterial load and neutrophil influx, and increased nitric oxide (NO) production in the peritoneal cavity. With regard to oxidative status, SGE increased antioxidant defenses as measured by Trolox equivalent antioxidant capacity (TEAC) and glutathione (GSH), while reducing levels of the oxidative stress marker malondialdehyde (MDA). Altogether, these data suggest that SGE plays a protective role in septic animals, contributing to oxidative and inflammatory balance during sepsis. Therefore, Ae. aegypti SGE is a potential source for new therapeutic molecule(s) in polymicrobial sepsis, and this effect seems to be mediated by the control of inflammation and oxidative damage

Desafios na formação de enfermeiros na perspectiva dos egressos/Challenges in training nurses from the perspective of graduates

Objetivo: Descrever o perfil do egresso de enfermagem de uma instituição pública e relacionar o processo de formação em enfermagem com seu agir profissional. Metodologia: Estudo descritivo, transversal, com abordagem quanti-qualitativa. Participaram 61 egressos que se formaram no período de 2010 a 2016. Utilizou-se questionário semiestruturado via Google docs. A análise das questões objetivas foi realizada por meio de frequência simples e proporções. Os dados qualitativos foram analisados pelo método de análise de conteúdo e o corpus textual organizado no software IRAMUTEQ 0.7 Alfa2. Resultados: O perfil dos egressos demonstrou predominância do sexo feminino. A maioria trabalha na assistência, com renda de até 5 salários mínimos e estavam satisfeitos com o curso, contudo, metade dos egressos faria outro curso superior. Identificou-se deficiência na formação, especialmente no que tange a vivência prática e no gerenciamento de enfermagem. Conclusão: Os desafios e as fragilidades na formação elencados pelos egressos apontam para necessidade de mudanças no que diz respeito à estrutura dos cursos de enfermagem, bem como a organização do Estágio Curricular Supervisionado e da vivência prática durante a graduação

Reliability of streetscape audits comparing on‐street and online observations : MAPS-Global in 5 countries

Background: Microscale environmental features are usually evaluated using direct on-street observations. This study assessed inter-rater reliability of the Microscale Audit of Pedestrian Streetscapes, Global version (MAPS-Global), in an international context, comparing on-street with more efficient online observation methods in five countries with varying levels of walkability. Methods: Data were collected along likely walking routes of study participants, from residential starting points toward commercial clusters in Melbourne (Australia), Ghent (Belgium), Curitiba (Brazil), Hong Kong (China), and Valencia (Spain). In-person on the street and online using Google Street View audits were carried out by two independent trained raters in each city. The final sample included 349 routes, 1228 street segments, 799 crossings, and 16 cul-de-sacs. Inter-rater reliability analyses were performed using Kappa statistics or Intraclass Correlation Coefficients (ICC). Results: Overall mean assessment times were the same for on-street and online evaluations (22 ± 12 min). Only a few subscales had Kappa or ICC values < 0.70, with aesthetic and social environment variables having the lowest overall reliability values, though still in the "good to excellent" category. Overall scores for each section (route, segment, crossing) showed good to excellent reliability (ICCs: 0.813, 0.929 and 0.885, respectively), and the MAPS-Global grand score had excellent reliability (ICC: 0.861) between the two methods. Conclusions: MAPS-Global is a feasible and reliable instrument that can be used both on-street and online to analyze microscale environmental characteristics in diverse international urban settings

A Gene Expression Signature to Select Hepatocellular Carcinoma Patients for Liver Transplantation

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.OBJECTIVE: To propose a new decision algorithm combining biomarkers measured in a tumor biopsy with clinical variables, to predict recurrence after liver transplantation (LT). SUMMARY BACKGROUND DATA: Liver cancer is one of the most frequent causes of cancer-related mortality. LT is the best treatment for hepatocellular carcinoma (HCC) patients but the scarcity of organs makes patient selection a critical step. Additionally, clinical criteria widely applied in patient eligibility decisions miss potentially curable patients while selecting patients that relapse after transplantation. METHODS: A literature systematic review singled out candidate biomarkers whose RNA levels were assessed by quantitative PCR in tumor tissue from 138 HCC patients submitted to LT (>5 y follow up, 32% beyond Milan criteria). The resulting four gene signature was combined with clinical variables to develop a decision algorithm using machine learning approaches. The method was named HepatoPredict. RESULTS: HepatoPredict identifies 99% disease-free patients (>5 y) from a retrospective cohort, including many outside clinical criteria (16%-24%), thus reducing the false negative rate. This increased sensitivity is accompanied by an increased positive predictive value (88,5%-94,4%) without any loss of long-term overall survival or recurrence rates for patients deemed eligible by HepatoPredict; those deemed ineligible display marked reduction of survival and increased recurrence in the short and long term. CONCLUSIONS: HepatoPredict outperforms conventional clinical-pathologic selection criteria, (Milan, UCSF) providing superior prognostic information. Accurately identifying which patients most likely benefit from LT enables an objective stratification of waiting lists and information-based allocation of optimal versus suboptimal organs.publishersversionepub_ahead_of_prin

práticas artísticas no ensino básico e secundário

Para este número 18 da Revista Matéria-Prima reuniram-se 16 artigos que permitem colocar em perspetiva diversas dimensões da Educação Artística. Entre a consciência patrimonial e a emancipação, entre o domínio da técnica e do género, entre a integração e a maturação criadora, há um espaço a ser pesquisado, feito de história, de identidade, de ensaio e de inclusividadeinfo:eu-repo/semantics/publishedVersio

A National Wide Collaborative Study

INTRODUCTION: Even though the risk of COVID-19 in pregnancy may be increased, large-scale studies are needed to better understand the impact of the infection in this population. The aim of this study is to describe obstetric complications and the rate of vertical transmission in pregnant women with SARS-CoV-2 infection. MATERIAL AND METHODS: Detected cases of SARS-CoV-2 infection in pregnancy were registered in Portuguese hospitals by obstetricians. Epidemiological, pregnancy and childbirth data were collected. RESULTS: There were 630 positive cases in 23 Portuguese maternity hospitals, most at term (87.9%) and asymptomatic (62.9%). The most frequent maternal comorbidity was obesity. The rates of preterm birth and small-to-gestational-age were 12.1% and 9.9%, respectively. In the third trimester, 2.9% of pregnant women required respiratory support. There were eight cases (1.5%) of fetal death, including two cases of vertical transmission. There were five cases of postpartum respiratory degradation, but no maternal deaths were recorded. The caesarean section rate was higher in the first than in the second wave (68.5% vs 31.5%). RT-PCR SARS-CoV-2 positivity among newborns was 1.3%. CONCLUSION: SARS-Cov-2 infection in pregnancy may carry increased risks for both pregnant women and the fetuses. Individualized surveillance and the prophylaxis of this population with vaccination. is recommended in these cases.publishersversionepub_ahead_of_prin

Impact of EGFR genetic variants on glioma risk and patient outcome

B.M. Costa and M. Viana-Pereira contributed equally to this work; The authors thank the Immunochemotherapy Department of Hospital S. Marcos, and Clinica Laboratorial Dr. Edgar Botelho Moniz, S. Tirso, Portugal, for their helpful assistance in the management of controlsBACKGROUND: The epidermal growth factor receptor (EGFR) regulates important cellular processes and is frequently implicated in human tumors. Three EGFR polymorphisms have been described as having a transcriptional regulatory function: two single-nucleotide polymorphisms in the essential promoter region, -216G/T and -191C/A, and a polymorphic (CA)(n) microsatellite sequence in intron 1. We aimed to elucidate the roles of these EGFR polymorphisms in glioma susceptibility and prognosis. METHODS: We conducted a case-control study with 196 patients with glioma and 168 cancer-free controls. Unconditional multivariate logistic regression models were used to calculate ORs and 95% confidence intervals. A Cox regression model was used to evaluate associations with patient survival. False-positive report probabilities were also assessed. RESULTS: None of the EGFR -216G/T variants was significantly associated with glioma risk. The -191C/A genotype was associated with higher risk for glioma when the (CA)(n) alleles were classified as short for ≤16 or ≤17 repeats. Independently of the (CA)(n) repeat cutoff point used, shorter (CA)(n) repeat variants were significantly associated with increased risk for glioma, particularly glioblastoma and oligodendroglioma. In all tested models with different (CA)(n) cutoff points, only -191C/A genotype was consistently associated with improved survival of patients with glioblastoma. CONCLUSIONS: Our findings implicate EGFR -191C/A and the (CA)(n) repeat polymorphisms as risk factors for gliomas, and suggest -191C/A as a prognostic marker in glioblastoma. Impact: Our data support a role of these EGFR polymorphisms in determining glioma susceptibility, with potential relevance for molecularly based stratification of patients with glioblastoma for individualized therapies.Schering-Plough Farma, PortugalFundação para a Ciência e a Tecnologia (FCT) - SFRH/BPD/33612/2009; SFRH/BD/29145/200