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Background: Selective cyclooxygenase-2 inhibitor anti-inflammatory drugs (coxibs) are associated with the development of adverse events, mainly gastrointestinal and cardiovascular, but renal effects are less known. Objective: To assess the renal risks of coxibs compared to placebo by means of a systematic review and meta-analysis. Methods: Randomized controlled trials that assessed renal effects of coxibs (celecoxib, etoricoxib, lumiracoxib, parecoxib, and valdecoxib) were searched in PubMed, Embase, Scopus and other sources up to March 2024. Two independent reviewers performed study screening, data extraction, and risk of bias assessment. Random effect meta-analysis was employed to calculate the relative risks (RR) and 95% confidence intervals (CI) of renal effects of coxibs compared to placebo and inconsistency among studies (I2). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. Results: Out of 5284 retrieved records, 49 studies (comprising 46 reports) were included. Coxibs increased the risk of edema (RR 1.46; 95% CI 1.15, 1.86; I2 = 0%; 34 studies, 19,754 participants; moderate-certainty evidence), and celecoxib increased hypertensive or renal events (RR 1.24; 95% CI 1.08, 1.43; I2 = 0%; 2 studies, 3589 participants; moderate-certainty evidence). Etoricoxib increased the risk of hypertension (RR 1.98; 95% CI 1.14, 3.46; I2 = 34%; 13 studies, 6560 participants; moderate-certainty evidence); no difference was observed when pooling all coxibs (RR 1.26; 95% CI 0.91, 1.76; I2 = 26%; 30 studies, 16,173 participants; moderate-certainty evidence). Conclusions: Coxibs likely increase the renal adverse effects, including hypertension and edema. Awareness about the renal risks of coxibs should be increased, mainly in high-risk patient.

Introduction: Some studies show that participants do not always fully understand the informed consent form (ICF), which is one of the reasons for dropouts. This study aimed to adapt the Quality of Informed Consent (QuIC) questionnaire into a valid instrument to be applied to the Portuguese population and to measure its reliability and validity in the Portuguese population, by applying it to a sample of participants in controlled trials. Methods: The QuIC questionnaire was developed to assess the quality of informed consent in clinical trials and consists of two parts, addressing both the objective (part A) and the subjective (part B) understanding. After being translated and validated into Portuguese, it was implemented in 100 cardiac participants of phase III clinical trials in a University Hospital Center. Results: The QuIC-PT questionnaire showed excellent stability over time and good validity. All patients evaluated their participation and their health positively and recognized the main purpose of the clinical trial. Almost all participants understood their role in helping future patients and the purpose of the trial and realized that, by signing the ICF, they were participating in a clinical trial. However, none of them knew that their experimental treatment was not proven to be the best alternative for their condition. Conclusion: The QuIC-PT questionnaire seems to be a valid and useful instrument to evaluate the participants’ understanding of the ICF. In this study, we found that some concepts, like ‘study protocol’ or ‘randomization’, were not well understood by participants when signing the ICF, especially by participants with lower education levels. They also believed that the experimental intervention would solve their health condition. Greater awareness about the importance of the informed consent process and ICF is necessary so that participants can fully understand the protocol, especially the risks involved, and their rights as participants.

Abstract Generative Artificial Intelligence can be an important asset in the drug discovery process to meet the demand for novel medicines. This work outlines the optimization and fine-tuning steps of MedGAN, a deep learning model based on Wasserstein Generative Adversarial Networks and Graph Convolutional Networks, developed to generate new quinoline-scaffold molecules from complex molecular graphs, including hyperparameter adjustments and evaluations of drug-likeness attributes such as pharmacokinetics, toxicity, and synthetic accessibility. The best model was capable of generating 25% valid molecules, 62% fully connected, from which 92% were quinolines, 93% were novel, and 95% unique, preserving chirality, atom charge, and favorable drug-like properties while generating 4831 novel quinolines. These results provide valuable insights into how activation functions, optimizers, learning rates, neuron units, molecule size and constitution, and scaffold structure affect the performance of generative models and their potential to create new molecular structures, enhancing deep learning applications in computational drug design.

Body mass index has been studied as one of the factors that negatively influences COVID-19. In this work, we intend to analyze this influence. A representative sample of the population of Beira Interior was used (around 2%), on which immunity research and a socio-demographic survey were carried out. It was found that obesity influences the vaccination rate, and that all other variables analyzed were not influenced by body mass index.

Objectives: To estimate the prevalence of antidepressant use in Brazil. Methods: We conducted a systematic review with searches in MEDLINE, Embase, Scopus, LILACS, and SciELO up to May 2023. Two researchers independently selected studies, extracted data, and assessed the methodological quality. We pooled the prevalence of antidepressant use using meta-analyses of proportions (Freeman-Tukey transformation) and estimated heterogeneity by the I2 statistic. OR meta-analyses of antidepressant use by sex were calculated (men as reference) and between-study variation was explored by meta-regressions. Results: Out of 3,299 records retrieved, 23 studies published in 28 reports were included, with a total of 75,061 participants. The overall prevalence of antidepressant use was 4.0% (95%CI 2.7-5.6%; I2 = 98.5%). Use of antidepressants in the previous 3 days was higher in women (12.0%; 95%CI 9.5-15.1%; I2 = 0%) than men (4.6%; 95%CI 3.1-6.8%; I2 = 0%) (p < 0.001; OR = 2.82; 95%CI 1.72-4.62). Gender differences were particularly higher for antidepressant use in the previous year (women: 2.3%; 95%CI 1.6-3.1; I2 = 37.6% vs. men: 0.5%; 95%CI 0.2-1.0%; I2 = 0%, p < 0.001; OR = 4.18; 95%CI 2.10-8.30). Between-study variation in the overall prevalence of antidepressant use significantly increased with mean participant age (p = 0.035; residual I2 = 0%; regression coefficient = 0.003). Conclusion: Four out of every 100 Brazilians used antidepressants in this 3-decade assessment. Use increased with age and was more prevalent in women compared to men. Registration number: PROSPERO CRD42022345332.

Diabetes can cause several long-term complications. Knowledge about this disease can play an important role in reducing diabetes-related complications. In addition, the lack of awareness leads to misconceptions, which joined with inadequate knowledge, are relevant barriers to proper diabetes management. In this study, we aimed to assess the diabetes knowledge of a type 2 diabetes (T2D) population and identify major knowledge gaps, in order to prevent complications and to increase quality of life. In a cross-sectional, observational study in a convenience sample, we identified individuals diagnosed with T2D attending ambulatory visits from five health settings, older than 18 years, with a time diagnosis of at least 1 year, and attending multidisciplinary visits for at least 3 months. To assess the knowledge of T2D individuals, we applied the Portuguese version of the Diabetes Knowledge Test. The sample included a total of 1,200 persons, of whom almost half were female. The age range of the participants varied from 24 to 94 years old, and the mean age was 65.6 ± 11.4 years. Most of the sample had a level of education under secondary and lived with someone. In our sample, 479 (39.9%) were insulin-treated. The percentage of correct answers was 51.8% for non-insulin vs. 58.7% for insulin treated (p

The purpose of this study was to explore the relationships between sociodemographic, clinical, and psychological variables and their contribution towards family functioning during the first wave of COVID-19 in Portugal. The COVID-19 pandemic was an overwhelming and stressful life event with social consequences that impacted family functioning and contributed to multilevel disruptions. The study used a cross-sectional design and included 110 participants (94 women), with a mean age of 35.71 (SD = 13.53). Participants answered self-report measures assessing family satisfaction, hope, psychological well-being, risk perception, and family functioning. Hope (pathways subscale) played a moderating role in the relationship between family satisfaction and family functioning. Family satisfaction and psychological well-being partially mediated the relationship between hope and family functioning. Clinical relevance and implications for further research are addressed. Intervention should focus on increasing psychological well-being and hope together with family satisfaction in order to promote family functioning. For those individuals struggling with COVID-19 issues, mental health interventions are paramount.

Abstract Background Cervical cancer is a major concern to women’s health, being the fourth most common cancer worldwide. A great percentage of these cancer is consequence of an HPV infection, namely from specific genotypes such as 16/18. Portuguese screening program subjects women to a reflex cytology triage every 5 years. Aptima® HPV is a screening test which presents better specificity than other tests which are used in Portugal (Hybrid Capture® 2 and Cobas® 4800) and still have a comparable sensitivity. The present study aims to estimate the number of diagnostic tests and costs that are avoided using Aptima® HPV compared to the use of two other tests, Hybrid Capture® 2 and Cobas® 4800, within the cervical cancer screening programme in Portugal. Methods A model, consisting of a decision-tree, was developed to represent the full Portuguese screening program for cervical cancer. This model is used to compare the costs resulting from using Aptima® HPV test versus the other tests used in Portugal, during 2 years. Other outcomes such as the number of additional tests and exams were also computed. This comparison considers the performance of each test (sensitivity and specificity) and assumes an equal price for every test compared. Results Cost savings resulting from the use of Aptima® HPV are estimated at approximately €382 million versus Hybrid Capture® 2 and €2.8 million versus Cobas® 4800. Moreover, Aptima® HPV prevents 265,443 and 269,856 additional tests and exams when compared with Hybrid Capture® 2 and Cobas® 4800. Conclusions The use of Aptima® HPV resulted in lower costs as well as less additional test and exams. These values result from the greater specificity of Aptima® HPV, which signals less false positive cases and consequently avoids carrying out additional tests.

Introdução: Antidepressivos são medicamentos empregados para tratar ansiedade e depressão, e suas vendas têm crescido nos últimos anos no Brasil ¹, possivelmente refletindo o aumento da carga de doenças em saúde mental. Estudos de base populacional sobre a prevalência do uso de antidepressivos foram realizados em diferentes regiões do Brasil, mas não há uma síntese desses resultados, o que traria informação relevante sobre o consumo desses medicamentos. Objetivos: Estimar a prevalência do uso de antidepressivos na população brasileira por meio de revisão sistemática com meta-análise. Material e Método: Realizamos uma revisão sistemática da literatura seguindo um protocolo previamente registrado (CRD42022345332). As buscas foram realizadas em maio de 2023 nas seguintes bases de dados: MEDLINE, Embase, Scopus, LILACS e SciELO. Dois pesquisadores selecionaram independentemente os estudos, extraíram os dados e avaliaram a qualidade metodológica. Combinamos a prevalência de consumo de antidepressivos e intervalo de confiança de 95% (IC95%) usando meta-análises de proporções de Freeman-Tukey, com a heterogeneidade estimada pelo I². Adicionalmente foram calculadas meta-análises do odds ratio (OR) do uso de antidepressivos por sexo pelo método DerSimonian & Laird e metarregressões pelo método de Knapp-Hartung modificado para avaliar o efeito de variáveis na variabilidade da prevalência do uso de antidepressivos entre os estudos. Resultados: De 3.299 registros, foram incluídos 23 estudos publicados em 28 artigos. A prevalência geral de uso de antidepressivos foi de 4,0% (IC 95% 2,7-5,6%; I2=98,5%). O uso de antidepressivos nos 3 dias anteriores foi maior em mulheres (12,0%; IC 95% 9,5-15,1%; I²=0,0%) do que em homens (4,6%; IC 95% 3,1-6,8%; I²=0,0%), OR=2,82 (IC95% 1,72-4,62). As diferenças de gênero foram particularmente maiores para o uso de antidepressivos no ano anterior (mulheres: 2,3%; IC 95% 1,6-3,1; I2=37,6%; homens: 0,5%; IC 95% 0,2-1,0%; I²=0,0%; OR=4,18 [IC95% 2,10-8,30]). A prevalência pontual de uso de antidepressivos entre idosos foi maior do que em adultos no dia da entrevista (idosos: 12,2%; IC95% 4,3-23,4%; I²=97,3%; adultos: 5,6%; IC95% 1,8-11,3%; I²=96,1%). A variação da prevalência geral do uso de antidepressivos aumentou significativamente com a média de idade dos participantes (p=0,035; I² residual=0,0%; coeficiente de regressão=0,003). Discussão e Conclusões: Quatro em cada 100 brasileiros fazem uso de antidepressivos, sendo maior em mulheres do que em homens e em idosos em relação a adultos. Investimentos em serviços farmacêuticos são necessários para monitorar o uso racional de antidepressivos na população brasileira, especialmente em indivíduos vulneráveis, como os idosos.

Introdução: Os anti-inflamatórios inibidores seletivos da cicloxigenase-2 podem causar eventos adversos graves, como sangramento gastrointestinal e eventos cardiovasculares, já documentados na literatura [1]. Os eventos adversos renais podem resultar em danos permanentes e afetar a qualidade de vida dos pacientes. Esses eventos são menos relatados [2] e precisam ser sistematicamente revisados. Material e Método: O protocolo desta revisão sistemática e meta-análise foi previamente registrado (PROSPERO: CRD42022380227). Ensaios clínicos randomizados que avaliaram os efeitos renais de anti- inflamatórios inibidores da cicloxigenase-2 (celecoxibe, etoricoxibe, lumiracoxibe, parecoxibe e valdecoxibe) em comparação com placebo foram elegíveis. Estratégias de busca com os descritores: ‘cox 2 inhibitor’, ‘coxib’, ‘kidney’, ‘renal’, ‘tolerability’, ‘safety’ foram elaboradas e aplicadas no PubMed, Embase, Central, Scopus e Web of Science em setembro de 2022. Os dados foram importados para a plataforma Covidence, onde dois revisores independentes avaliaram a elegibilidade, extraíram os dados e a qualidade dos estudos. Meta-análises foram conduzidas no software RevMan 5.4 utilizando o método de Mantel- Haenzel de efeitos aleatórios para calcular o risco relativo (RR) e intervalos de confiança de 95% (IC) dos efeitos renais investigados; a heterogeneidade foi estimada por meio do I2. A certeza da evidência gerada foi avaliada pelo método Grading of Recommendations Assessment, Development and Evaluation (GRADE) em baixa, muito baixa, moderada e alta. Resultados: 3.926 artigos foram identificados nas bases de dados selecionadas e 46 artigos (compreendendo 50 estudos) foram incluídos para análise. Celecoxibe aumentou o risco de eventos hipertensivos ou renais (RR 1,24; IC 95% 1,07 a 1,43; I2 7%; 2 estudos, 3.589 participantes; moderada certeza). Etoricoxibe aumentou o risco de hipertensão (RR 1,98; IC 95% 1,14 a 3,46; I2 34%; 13 estudos, 6.560 participantes; baixa certeza), mas nenhuma diferença foi observada ao agrupar todos os coxibes (RR 1,26; IC 95% 0,91 a 1,76; I2 25%; 27 estudos, 16.174 participantes; moderada certeza). Os coxibes aumentaram o risco de edema (RR 1,48; IC 95% 1,17 a 1,87; I2 0%; 35 estudos, 21.332 participantes; baixa certeza). Níveis de creatinina (RR 0.73; IC 95% 0.21, 2.55; I2 39%; 4 estudos, 3,195 participantes; muito baixa certeza), glicosúria (RR 0,40; IC 95% 0,11, 1,46; 1 estudo, 372 participantes; baixa certeza), hematúria (RR 1,81; IC 95% 0,60, 5,43; I2 0%; 2 estudos, 1.133 participantes; baixa certeza) e retenção urinária (RR 0,99; IC 95% 0,13, 7,55; I2 58%; 3 estudos, 476 participantes; muito baixa certeza) não foram afetados pelo uso de coxibes. Discussão e Conclusões: Os resultados obtidos sugerem que os inibidores seletivos da cicloxigenase-2 estão relacionados a um aumento do risco renal, incluindo hipertensão e edema. A conscientização sobre os riscos renais desses medicamentos deve ser aumentada.

In the Mediterranean basin, the structure and species composition of traditional landscapes have historically been shaped and maintained by human-driven disturbances, such as extensive livestock grazing. The cessation of these activities, which have partially replaced the role of natural disturbances, may lead to vegetation overgrowth and biomass accumulation, with potential adverse impacts on biodiversity, ecosystem functions and services. Recently, the use of livestock for ecosystem management, with the purpose of maintaining grazing disturbance and the associated ecosystem processes, has been gaining traction. Nevertheless, there is still limited evidence on the performance of such grazing interventions. This review assesses the state of the art regarding the use of livestock for ecosystem management in Mediterranean landscapes. It examines the association between the regime and duration of grazing interventions and their reported effects on ecosystems. The list of reviewed interventions (68 interventions, retrieved from 47 studies) covered a diverse range of landcover systems (from grasslands to forests), of grazing regimes (characterized by different levels of grazing intensity and livestock species), and of duration of grazing (from short-term, < 5 years to long-term grazing, > 20 years). Wildfire prevention and biomass control, biodiversity and habitat conservation and the regulation of soil quality are the main reasons for the use of grazing interventions. The results of this review suggest that the use of domestic herbivores in ecosystem management can contribute to wildfire prevention and biomass control, with these positive effects fading away in long-term grazing interventions. Goats seem to perform better than cattle for biomass control. The effects on biodiversity and habitat conservation depend on the grazing regime, with intensive grazing showing negative results, while the effects on soil quality are generally negative but require further assessment, due to data limitations.

Systems for managing municipal solid waste are typically ineffective in developing nations because of governments' deficient financial and administrative frameworks, poor rules, and a lack of suitable infrastructure and human resources. The informal sector plays an essential role in these systems by reprocessing waste into secondary raw materials, reducing collection and disposal costs, and, most importantly, benefiting the environment by avoiding incineration and landfilling. However, their actual contributions remain unknown. The present paper aims to understand the role of informal waste pickers (IWPs) in the waste management system of Guayaquil City and their environmental impact through the calculations of the carbon footprint (CF) avoided due to their aid. The survey design gathered information on their personal profiles, types, and rates of collected recyclables, market conditions, their main barriers, and troubles regarding their formalization. The results of the survey demonstrate that waste picking is mostly a male-driven activity, the average daily mass collected per IWP is 13 kg, the most collected recyclable waste is polyethylene terephthalate, their average monthly income is $179, and the total avoided CF of the entire informal waste picking process is almost 14 thousand tons of CO2 eq yearly. Further, IWPs prefer to operate alone, and only 16% of them would join a cooperative, despite their numerous financial, logistical, and personal challenges.

Human–animal relations have been a fruitful research topic worldwide. The importance of deer in hunter–gatherer societies is undeniable, with cervids being commonly found in archaeological and past artistic records, with a notable amount of information recovered in the Iberian Peninsula. This relevance continues during Late Prehistory, but the attempt to discuss cervids under broader perspectives and based on different types of data is not as common. We intend to approach human–deer relations in Central and Southern Portuguese Late Prehistory by considering the zooarchaeological records, both deer abundance in faunal spectra and their presence in “meaningful” assemblages and structured depositions, as well as the use of deer and deer body parts in other socio–cultural and ideological practices. The synthesis of available data shows that human–deer relations changed through time and space, with different abundances related to hunting depending on chronology and geography. The use of deer or their body parts as a resource of symbolic nature also varied, being included in food-sharing events, offerings, structured depositions, and graphic representations. Changeability is part of the different relationships, ontologies, and cosmogonies that humans and deer developed in the Late Prehistoric relational world.

The commercial space launch sector is currently undergoing a significant shift, with increasing competition and demand for launch services, as well as growing concerns about the environmental impact of rocket launches. To address these challenges, within the New Space Portugal project scope, a multidisciplinary framework for designing and optimizing new launch vehicles is proposed. Creating a more resilient and responsible space industry can be achieved by combining technological innovation and environmental sustainability, as emphasized by the framework. The main scope of the framework was to couple all the disciplines relevant to the space vehicle design in a modular way. Significant emphasis was placed on the infusion of ecodesign principles, including Life Cycle Assessment (LCA) considerations. Optimization techniques were employed to enhance the design and help designers conduct trade-off studies. In general, this multidisciplinary framework aims to provide a comprehensive approach to designing next-generation launch vehicles that meet the demands of a rapidly changing market while also minimizing their environmental impact. A methodology that leverages the strengths of both genetic and gradient-based algorithms is employed for optimizations with the objectives of maximizing the apogee altitude and minimizing the Global Warming Potential (GWP). Despite only being tested at the moment for sounding rockets, the framework has demonstrated promising results. It has illuminated the potential of this approach, leading to the identification of three optimal designs: one for maximizing the apogee, another for minimizing GWP, and a compromise design that strikes a balance between the two objectives. The outcomes yielded a maximum apogee of 6.41 km, a minimum GWP of 9.06 kg CO2eq, and a balanced compromise design featuring an apogee of 5.75 km and a GWP of 25.64 kg CO2eq.

The deep-sea covers over 70% of the Earth’s surface and harbors predominantly uncharacterized bacterial communities. Actinobacteria are the major prokaryotic source of bioactive natural products that find their way into drug discovery programs, and the deep-sea is a promising source of biotechnologically relevant actinobacteria. Previous studies on actinobacteria in deep-sea sediments were either regionally restricted or did not combine a community characterization with the analysis of their bioactive potential. Here we characterized the actinobacterial communities of upper layers of deep-sea sediments from the Arctic and the Atlantic (Azores and Madeira) ocean basins, employing 16S rRNA metabarcoding, and studied the biosynthetic potential of cultivable actinobacteria retrieved from those samples. Metabarcoding analysis showed that the actinobacterial composition varied between the sampled regions, with higher abundance in the Arctic samples but higher diversity in the Atlantic ones. Twenty actinobacterial genera were detected using metabarcoding, as a culture-independent method, while culture-dependent methods only allowed the identification of nine genera. Isolation of actinobacteria resulted on the retrieval of 44 isolates, mainly associated with Brachybacterium, Microbacterium, and Brevibacterium genera. Some of these isolates were only identified on a specific sampled region. Chemical extracts of the actinobacterial isolates were subsequently screened for their antimicrobial, anticancer and anti-inflammatory activities. Extracts from two Streptomyces strains demonstrated activity against Candida albicans. Additionally, eight extracts (obtained from Brachybacterium, Brevibacterium, Microbacterium, Rhodococcus, and Streptomyces isolates) showed significant activity against at least one of the tested cancer cell lines (HepG2 and T-47D). Furthermore, 15 actinobacterial extracts showed anti-inflammatory potential in the RAW 264.4 cell model assay, with no concomitant cytotoxic response. Dereplication and molecular networking analysis of the bioactive actinobacterial extracts showed the presence of some metabolites associated with known natural products, but one of the analyzed clusters did not show any match with the natural products described as responsible for these bioactivities. Overall, we were able to recover taxonomically diverse actinobacteria with different bioactivities from the studied deep-sea samples. The conjugation of culture-dependent and -independent methods allows a better understanding of the actinobacterial diversity of deep-sea environments, which is important for the optimization of approaches to obtain novel chemically-rich isolates.

Background Older patients are more likely to have medication-related problems, which are associated with changes in pharmacokinetics and pharmacodynamics, multimorbidity, and polypharmacy. Polypharmacy and inappropriate prescribing are well-known risk factors which commonly cause adverse clinical outcomes in older people. Prescribers struggle to identify potentially inappropriate medications and to choose an adequate tapering approach. Methods/design The goal of the study is to translate and culturally adapt MedStopper®, an original English language web-based decision aid system in deprescribing medication, to the Portuguese population. A translation-back translation method, with validation of the obtained Portuguese version of MedStopper® will be used, followed by a comprehension test. Discussion This is the first research in the Portuguese primary care setting that aims to provide a useful online tool for the appropriate prescription of older patients. The translated version in Portuguese version of the MedStopper® tool will represent an advance that seeks to continue improving the management of medications in the elderly. The adaptation into Portuguese of the educational tool provides clinicians with a screening tool to detect potentially inappropriate prescribing in patients older than 65 that reliable and easier to use. Trial registration Retrospectively registered.

Environmental awareness of the effects of single-use plastic packaging and the shortage of non-renewable resources have encouraged the search for alternative materials. Most of single-use plastic packaging is in the food sector, including bags, straws, bottle lids, coffee stirrers, soda and water bottles. Biopolymers and biocomposites have a high potential to be eco-friendly, economic and technically competitive with fossil-based plastics and conventional composites. This paper presents a case study of life-cycle analysis supporting the design and development of a bottle lid as food packaging by applying a life-cycle engineering methodology to select a biocomposite material. Two current materials with high density polyethylene (HDPE) and polylactic acid (PLA) and 10 alternative biocomposite materials of hybrid matrix (mixtures of HDPE and PLA) and contents of banana fibre (BF) were evaluated. The analysis is performed by integrating of life cycle assessment, life cycle cost and technical analysis. The results show that the material with higher BF content is the best alternative both technically and environmentally, while the material with lower BF content is the best alternative economically. Therefore, the importance attributed to each dimension of analysis is pondered and traded-off to allow an aggregated analysis of the alternatives and a well-informed decision-making.

Introduction: Depression is an emotional disorder associated with morbidities and disabilities worldwide. The growing use of antidepressants is a concern for health managers because there are still unanswered questions on the effectiveness and safety of these medicines. Drug sales have increased in Brazil in recent years, but investigations on antidepressants sales are not available. We aimed to describe the trends in the antidepressant commerce in Brazil in a five-year period.Materials and Methods: We performed an ecological study on antidepressant sales in Brazil, from November 2014 to October 2019, using data from IQVIA™, a data provider of pharmaceutical sales. Antidepressants were coded by the Anatomical Therapeutic Chemical classification system, and sales were presented in defined daily doses (DDDs) and DDDs per 1,000 inhabitants per day (DIDs). The results were expressed in absolute quantities and growth rates.Results: The analyzed dataset contained 23 active substances in 780 products. The total sales of antidepressants increased from 23.3 DIDs in November 2014 to 38.3 DIDs in October 2019 (p = 0.002). Selective serotonin reuptake inhibitors were the most sold category of drugs (+5.7 million DDDs) in the period. ‘Other’ antidepressants presented the largest growth rate (104.7%). Individually, the most sold active substance was escitalopram (+1.8 million DDDs), and vortioxetine had the largest growth rate (336.2%). Tricyclic sales remained unchanged, and monoamine oxidase inhibitors had low and even decreasing sales (−9.5%).Discussion: The total sales of antidepressants increased in Brazil from November 2014 to October 2019. The higher sale volumes of selective serotonin reuptake inhibitors and higher growth rate of ‘other’ antidepressants, with low sale volume of tricyclics and a decrease of monoamine oxidase inhibitors, suggest the replacement of older drugs by newer ones following a global trend. Therapeutic advances and commercial promotion efforts on new products might explain these findings.

Abstract Background During COVID-19 pandemic, healthcare workers (HCWs) have had high workload and have been exposed to multiple psychosocial stressors. The aim of this study was to evaluate HCWs in terms of the relative contributions of socio-demographic and mental health variables on three burnout dimensions: personal, work-related, and client-related burnout. Methods A cross-sectional study was performed using an online questionnaire spread via social networks. A snowball technique supported by health care institutions and professional organizations was applied. Results A total of 2008 subjects completed the survey. Gender, parental status, marriage status, and salary reduction were found to be significant factors for personal burnout. Health problems and direct contact with infected people were significantly associated with more susceptibility to high personal and work-related burnout. Frontline working positions were associated with all three dimensions. Higher levels of stress and depression in HCWs were significantly associated with increased levels of all burnout dimensions. Higher levels of satisfaction with life and resilience were significantly associated with lower levels of all burnout dimensions. Conclusions All three burnout dimensions were associated with a specific set of covariates. Consideration of these three dimensions is important when designing future burnout prevention programs for HCWs.

Objectives High-quality data are crucial for guiding decision-making and practising evidence-based healthcare, especially if previous knowledge is lacking. Nevertheless, data quality frailties have been exposed worldwide during the current COVID-19 pandemic. Focusing on a major Portuguese epidemiological surveillance dataset, our study aims to assess COVID-19 data quality issues and suggest possible solutions.Settings On 27 April 2020, the Portuguese Directorate-General of Health (DGS) made available a dataset (DGSApril) for researchers, upon request. On 4 August, an updated dataset (DGSAugust) was also obtained.Participants All COVID-19-confirmed cases notified through the medical component of National System for Epidemiological Surveillance until end of June.Primary and secondary outcome measures Data completeness and consistency.Results DGSAugust has not followed the data format and variables as DGSApril and a significant number of missing data and inconsistencies were found (eg, 4075 cases from the DGSApril were apparently not included in DGSAugust). Several variables also showed a low degree of completeness and/or changed their values from one dataset to another (eg, the variable ‘underlying conditions’ had more than half of cases showing different information between datasets). There were also significant inconsistencies between the number of cases and deaths due to COVID-19 shown in DGSAugust and by the DGS reports publicly provided daily.Conclusions Important quality issues of the Portuguese COVID-19 surveillance datasets were described. These issues can limit surveillance data usability to inform good decisions and perform useful research. Major improvements in surveillance datasets are therefore urgently needed—for example, simplification of data entry processes, constant monitoring of data, and increased training and awareness of healthcare providers—as low data quality may lead to a deficient pandemic control.

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Major depressive disorder (MDD) is a multidimensional psychiatric disorder that is estimated to affect around 350 million people worldwide. Generating valid and effective animal models of depression is critical and has been challenging for neuroscience researchers. For preclinical studies, models based on stress exposure, such as unpredictable chronic mild stress (uCMS), are amongst the most reliable and used, despite presenting concerns related to the standardization of protocols and time consumption for operators. To overcome these issues, we developed an automated system to expose rodents to a standard uCMS protocol. Here, we compared manual (uCMS) and automated (auCMS) stress-exposure protocols. The data shows that the impact of the uCMS exposure by both methods was similar in terms of behavioral (cognition, mood, and anxiety) and physiological (cell proliferation and endocrine variations) measurements. Given the advantages of time and standardization, this automated method represents a step forward in this field of preclinical research.

Resumo: Desde 1963 que a farmacovigilância foi reconhecida como uma área prioritária na saúde pública a nível global pela Organização Mundial da Saúde, garantindo a monitorização permanente da segurança dos medicamentos. O objetivo deste trabalho foi caracterizar as reações adversas a medicamentos recebidas pela Unidade de Farmacovigilância do Porto (UFPorto), Portugal, ao longo de duas décadas de atividade. Foram consideradas todas as notificações de suspeitas de reações adversas a medicamentos recebidas entre janeiro de 2001 e dezembro de 2019. Foram calculadas as taxas de notificação anuais, assim como a sua distribuição por origem, tipo de notificador e local de exercício da atividade, gravidade, conhecimento prévio e causalidade das reações adversas a medicamentos notificadas. No período em estudo, a UFPorto recebeu 9.711 notificações de suspeitas de reações adversas a medicamentos. As instituições hospitalares são aquelas que mais notificam (n = 6.003; 64%), assim como o médico entre os profissionais de saúde (n = 5.284; 54,4%). Os eventos adversos mais frequentemente reportados são graves (n = 6.275; 72%) e encontram-se descritos no respectivo Resumo das Características do Medicamento (n = 6.978; 72%). À maioria das notificações avaliadas pela UFPorto foi atribuído o grau de causalidade “provável” (n = 7.473; 77%), independentemente do tipo de notificador. Os resultados obtidos são concordantes com outros dados previamente reportados na literatura médica internacional e em relatórios oficiais nacionais. Contudo, continua-se a verificar taxas de subnotificação acentuadas, face ao esperado. Ao longo de aproximadamente 20 anos de atividade da UFPorto, tem-se verificado um aumento da sua atividade nas diversas vertentes da segurança do medicamento.

Technological development has had huge impacts in sports performance throughout the years, fostering the development of specific materials and manufacturing processes for sports-related products. Within this context, a new technology for snowboards was developed taking advantage of the internal coupling effects of Fibre Reinforced Plastics (FRP) using an anisotropic layer design. This work deals with the technical, economic and environmental evaluation of a snowboard made of three alternative materials, namely carbon, glass and flax fibre reinforced plastics. It shows how a life cycle analysis can support the design and development of products by applying a Life Cycle Engineering methodology to the design process of a snowboard using an innovative technology. In this case, both the material choice and the fiber placement angles have a significant impact on the stiffness of the resulting FRP and thus in the three dimensions of analysis - cost, environmental and technical. The natural fiber is the most sustainable option environmentally, the glass fiber is the best one economically and the carbon fibre is the best in terms of technical performance. Therefore, the importance attributed to each dimension of analysis is pondered and traded-off to allow an aggregated analysis of the alternatives and a well-informed decision-making.

One of the most intriguing dogmas in neurosciences—the empirical lack of brain neuronal regeneration in adulthood onwards to late life—began to be debunked initially by research groups focused on understanding postnatal (early days/weeks of murine and guinea pigs) neurodevelopmental and neuroplastic events [...]

Introduction Rational prescribing for older adults is a challenge because they usually exhibit multimorbidity and multimedication. One available and reliable tool to tackle this issue consists of the Screening Tool of Older People’s Prescriptions (STOPP) and the Screening Tool to Alert to Right Treatment (START), which has been associated with improvements in clinical outcomes. Our goal here is to translate and validate the STOPP-START screening tool for use with Portuguese general practitioners/family physicians.Methods and analysis The study will be conducted in four phases: phase I—translation of the STOPP-START screening tool to Portuguese; phase II—data collection of patient data; phase III—intrarater reliability and agreement study; and phase IV—inter-rater reliability and agreement study.Ethics and dissemination This study was approved by the Ethics Committee of the Central Health Region of Portugal (where the study will take place). Every participant will sign a written consent form. We intend to publish the full article in a related peer-reviewed journal, conference presentations, reports and in a PhD thesis.

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Gastric and colorectal cancers have a high incidence and mortality worldwide. The presence of cancer stem cells (CSCs) within the tumor mass has been indicated as the main reason for tumor relapse, metastasis and therapy resistance, leading to poor overall survival. Thus, the elimination of CSCs became a crucial goal for cancer treatment. The identification of these cells has been performed by using cell-surface markers, a reliable approach, however it lacks specificity and usually differs among tumor type and in some cases even within the same type. In theory, the ideal CSC markers are those that are required to maintain their stemness features. The knowledge that CSCs exhibit characteristics comparable to normal stem cells that could be associated with the expression of similar transcription factors (TFs) including SOX2, OCT4, NANOG, KLF4 and c-Myc, and signaling pathways such as the Wnt/β-catenin, Hedgehog (Hh), Notch and PI3K/AKT/mTOR directed the attention to the use of these similarities to identify and target CSCs in different tumor types. Several studies have demonstrated that the abnormal expression of some TFs and the dysregulation of signaling pathways are associated with tumorigenesis and CSC phenotype. The disclosure of common and appropriate biomarkers for CSCs will provide an incredible tool for cancer prognosis and treatment. Therefore, this review aims to gather the new insights in gastric and colorectal CSC identification specially by using TFs as biomarkers and divulge promising drugs that have been found and tested for targeting these cells.

The authors wish to make the following corrections to this paper [...]

Adverse drug reactions (ADR) significantly impact mortality and morbidity and lead to high healthcare costs. Reporting ADR to regulatory authorities allows for monitoring the safety and efficacy profile of medicines on the market and for assessing the benefit–risk ratio. This retrospective study aims to characterize the ADR profile of the most consumed antibiotics in Portugal that are prescribed for upper airway infections and submitted to the EudraVigilance database. The variables were analyzed in an exploratory perspective, through absolute and relative frequencies, with emphasis on serious ADR. A total of 59,022 reports were analyzed of which 64.4% were classified as suspected serious ADR. According to serious ADR, the female sex (52.2%) and 18–64 age group (47.5%) prevail. Health professionals reported 87.8% of suspected serious ADR and European Economic Area (EEA) countries represented 50.8% of the reports. “Skin and subcutaneous tissue connections” (15.9%), “general disorders and administrations site conditions” (12%), and “gastrointestinal disorders” (9.8%) are the prevalent system organ classes. In 4.5% of the reports, patients had a fatal outcome. A periodic evaluation of the safety of the antibiotic should be performed to facilitate the development of guidelines and policies to reduce the frequency of serious ADR.

Exposure to methamphetamine (Meth) has been classically associated with damage to neuronal terminals. However, it is now becoming clear that addiction may also result from the interplay between glial cells and neurons. Recently, we demonstrated that binge Meth administration promotes microgliosis and microglia pro-inflammation via astrocytic glutamate release in a TNF/IP3R2-Ca2+-dependent manner. Here, we investigated the contribution of neuronal cells to this process. As the crosstalk between microglia and neurons may occur by contact-dependent and/or contact-independent mechanisms, we developed co-cultures of primary neurons and microglia in microfluidic devices to investigate how their interaction affects Meth-induced microglia activation. Our results show that neurons exposed to Meth do not activate microglia in a cell-autonomous way but require astrocyte mediation. Importantly, we found that neurons can partially prevent Meth-induced microglia activation via astrocytes, which seems to be achieved by increasing arginase 1 expression and strengthening the CD200/CD200r pathway. We also observed an increase in synaptic individual area, as determined by co-localization of pre- and post-synaptic markers. The present study provides evidence that contact-dependent mechanisms between neurons and microglia can attenuate pro-inflammatory events such as Meth-induced microglia activation.

The deep-sea constitutes a true unexplored frontier and a potential source of innovative drug scaffolds. Here, we present the genome sequence of two novel marine actinobacterial strains, MA3_2.13 and S07_1.15, isolated from deep-sea samples (sediments and sponge) and collected at Madeira archipelago (NE Atlantic Ocean; Portugal). The de novo assembly of both genomes was achieved using a hybrid strategy that combines short-reads (Illumina) and long-reads (PacBio) sequencing data. Phylogenetic analyses showed that strain MA3_2.13 is a new species of the Streptomyces genus, whereas strain S07_1.15 is closely related to the type strain of Streptomyces xinghaiensis. In silico analysis revealed that the total length of predicted biosynthetic gene clusters (BGCs) accounted for a high percentage of the MA3_2.13 genome, with several potential new metabolites identified. Strain S07_1.15 had, with a few exceptions, a predicted metabolic profile similar to S. xinghaiensis. In this work, we implemented a straightforward approach for generating high-quality genomes of new bacterial isolates and analyse in silico their potential to produce novel NPs. The inclusion of these in silico dereplication steps allows to minimize the rediscovery rates of traditional natural products screening methodologies and expedite the drug discovery process.

Deep-sea sediments (DSS) are one of the largest biotopes on Earth and host a surprisingly diverse microbial community. The harsh conditions of this cold environment lower the rate of natural attenuation, allowing the petroleum pollutants to persist for a long time in deep marine sediments raising problematic environmental concerns. The present work aims to contribute to the study of DSS microbial resources as biotechnological tools for bioremediation of petroleum hydrocarbon polluted environments. Four deep-sea sediment samples were collected in the Mid-Atlantic Ridge, south of the Azores (North Atlantic Ocean). Their autochthonous microbial diversity was investigated by 16S rRNA metabarcoding analysis. In addition, a total of 26 deep-sea bacteria strains with the ability to utilize crude oil as their sole carbon and energy source were isolated from the DSS samples. Eight of them were selected for a novel hydrocarbonoclastic-bacterial consortium and their potential to degrade petroleum hydrocarbons was tested in a bioremediation experiment. Bioaugmentation treatments (with inoculum pre-grown either in sodium acetate or petroleum) showed an increase in degradation of the hydrocarbons comparatively to natural attenuation. Our results provide new insights into deep-ocean oil spill bioremediation by applying DSS hydrocarbon-degrading consortium in lab-scale microcosm to simulate an oil spill in natural seawater.

In Portugal, the potent paralytic shellfish toxins (PSTs) have appeared irregularly since the onset of a national monitoring program for marine biotoxins in 1986. In years where high contamination levels were attained in bivalves, sporadic cases of human poisonings have been recorded, as in 1994 and 2007. The reappearance of high contamination levels led to the appearance of new cases during the autumn of 2018. This study details toxin ingestion, symptomatology and toxin elimination and metabolization in the fluids of two patients, who ingested mussels from the Portuguese southwest coast and required hospitalization due to the severity of symptoms. Toxin elimination was confirmed by ELISA in plasma and urine samples. In mussel samples, the toxin profile obtained by HPLC-FLD displayed a wide diversity of toxins, typical of Gymnodinum catenatum ingestion. However, in the urine samples, the toxin profile was reduced to B1 and dcSTX. Abundant compounds in mussels having an O-sulphate at C11, such as C1+2 and dcGTX2+3, were absent in urine. In plasma, PSTs were not detected by HPLC-FLD. Calculated toxin ingestion, resulting from consumption of an estimated 200-g portion, was in the range of 104–120 μg STX eq./kg b. w. Keywords: Paralytic shellfish poisoning, Saxitoxin, Seafood poisoning, Human samples, HPLC, ELISA, Portugal

Nature is the major reservoir of biologically active molecules. The urgent need of finding novel molecules for pharmaceutical application is prompting the research of underexplored environments, such as marine ecosystems. Here, we investigated cultivable actinobacteria associated with the macroalgae Laminaria ochroleuca and assessed their potential to produce compounds with antimicrobial or anticancer activities. A specimen of L. ochroleuca was collected in a rocky shore in northern Portugal, and fragments of tissues from different parts of the macroalgae (holdfast, stipe, and blades) were surface sterilized and plated in three culture media selective for actinobacteria. A total of 90 actinobacterial strains were isolated, most of which affiliated with the genus Streptomyces. Isolates associated with the genera Isoptericola, Rhodococcus, Nonomuraeae, Nocardiopsis, Microbispora, and Microbacterium were also obtained. Organic extracts from the isolates were tested for their antimicrobial activity using the agar-based disk diffusion method, followed by determination of minimum inhibitory concentration (MIC) values. Forty-five isolates inhibited the growth of Candida albicans and/or Staphylococcus aureus, with MIC values ranging from

Natural compounds have had increasing applications in the biotechnological sector, with a large fraction of these substances being channeled to the pharmaceutical industry due to their important pharmacological properties. The discovery of new bioactive molecules with novel mechanisms of action constitutes a promising solution for the design of alternative therapeutic solutions. Actinobacteria are a large group of morphologically and physiologically diverse bacteria well known for their production of biotechnologically relevant compounds. The Portuguese coast is scantly explored in terms of Actinobacteria diversity and respective bioactive potential, offering a good opportunity to find new Actinobacteria taxa and bioactive natural products. In this study, we investigated the Actinobacteria diversity associated with a sediment sample collected from the intertidal zone of a beach in northern Portugal, through a cultivation-dependent approach, and screened its antimicrobial and cytotoxic potential. A total of 52 Actinobacteria strains were recovered from the marine sediment, with the largest fraction of the isolates belonging to the genus Micromonospora. Bioactivity screening assays identified crude extracts of six Streptomyces strains active against C. albicans, exhibiting minimum inhibition concentration (MIC) values in the range of 3.90–125 μg mL−1. Twenty-five Actinobacteria crude extracts (obtained from strains of the genera Micromonospora, Streptomyces and Actinomadura) exhibited significant effects on the viability of at least one tested cancer cell line (breast ductal carcinoma T-47D and liver hepatocellular carcinoma HepG2). The Actinobacteria extracts demonstrating activity in the antimicrobial and/or cytotoxic assays were subjected to metabolomic analysis (Mass spectrometry (MS)-based dereplication and molecular networking analyses), indicating the presence of four clusters that may represent new natural products. The results obtained demonstrate the importance of bioprospecting underexplored environments, like the Portuguese coast, for enhancing the discovery of new natural products, and call attention to the relevance of preserving the natural genetic diversity of coastal environments.

Industrial cooking of common octopus (Octopus vulgaris) under well-established procedures is advantageous for current consumers, which demand healthy and convenient food. This work aimed to evaluate the effect of industrial water boiling, without the addition of salt, on the nutritional profile of common octopus. True retentions (TRs) were calculated for essential nutrients and toxic elements. After boiling, the moisture content decreased, resulting in a concentration of other constituents (protein, fat, fatty acids, majority of amino acids, phosphorus, zinc, and iodine). High TRs were obtained for some essential nutrients: 90.2% (eicosapentaenoic acid, EPA), 89.1% (docosahexaenoic acid, DHA), ≥74.6% (indispensable amino acids, IAA), and 86.8% (iodine). In both raw and boiled octopus, polyunsaturated fatty acids (252.2 and 425.1 mg/100 g), leucine (940.1 and 1613.4 mg/100 g), glutamate (1971.5 and 3257.1 mg/100 g), sodium (393.3 and 332.5 mg/100 g), and zinc (12.6 and 16.6 mg/kg) were, respectively, the most abundant fatty acids, IAA, dispensable amino acids, macro, and micro elements. Cadmium, lead, and mercury levels found in boiled octopus were 0.02, 0.10, and 0.08 mg/kg, respectively. The consumption of 150 g (usual portion) of boiled octopus is advisable because it contributes to significant daily intakes of EPA+DHA (>100%), selenium (75.6%), and iodine (12.4%), and 25% of the daily adequate intake of sodium for adults.

OBJETIVO: Avaliar os resultados de intervenção para melhoria da quantidade e relevância das notificações de reacções adversas a medicamentos. MÉTODOS: Foi implementado um estudo controlado aleatorizado, por agrupamentos em farmacêuticos a exercer actividade profissional na região norte de Portugal, em 2007. Após aleatorização, 364 indivíduos foram alocados ao grupo de intervenção (261 na intervenção telefónica e 103 nos workshops); o grupo de controlo foi constituído por 1.103 farmacêuticos. Na intervenção educativa foram abordados a problemática das reacções adversas a medicamentos, o impacto na saúde pública e a notificação espontânea. Quanto à relevância, as reações adversas foram classificadas em graves e inesperadas. A análise estatística foi efectuada com base no princípio intention-to-treat; aplicaram-se modelos lineares generalizados mistos, utilizando o método penalized quasi-likelihood. Os farmacêuticos estudados foram seguidos durante um período de 20 meses. RESULTADOS: A intervenção aumentou três vezes a taxa de notificação espontânea das reações adversas (RR = 3,22; IC 95%: 1,33; 7,80) relativamente ao grupo de controlo. Houve incremento da relevância das notificações com aumento das reações adversas graves em cerca de quatro vezes (RR = 3,87; IC 95%: 1,29;11,61) e inesperadas em cinco vezes (RR = 5,02; IC 95%: 1,33;18,93), relativamente ao grupo de controlo. CONCLUSÕES: As intervenções educativas aumentam significativamente, por até quatro meses, a quantidade e a relevância das notificações espontâneas de reacções adversas a medicamentos por parte dos farmacêuticos da região norte de Portugal.OBJETIVO: Evaluar los resultados de intervención para mejoría de la cantidad y relevancia de las notificaciones de reacciones adversas a medicamentos. MÉTODOS: Fue implementado un estudio controlado aleatorio, por agrupaciones de farmacéuticos que ejercen actividad profesional en la región norte de Portugal, en 2007. Posterior a la aleatoriedad, 364 individuos fueron distribuidos en el grupo de intervención (261 en la intervención telefónica y 103 en los workshops); el grupo control fue constituido por 1.103 farmacéuticos. En la intervención educativa fueron abordados la problemática de las reacciones adversas a medicamentos, el impacto en la salud pública y la notificación espontánea. Con relación a la relevancia, las reacciones adversas fueron clasificadas en graves e inesperadas. El análisis estadístico fue efectuado con base en el principio intention-to-treat; se aplicaron modelos lineares generalizados mixtos, utilizando el método penalized quasi-likelihood. Los farmacéuticos estudiados fueron seguidos durante un período de 20 meses. RESULTADOS: La intervención aumentó tres veces la tasa de notificación espontánea de las reacciones adversas (RR=3,22; IC95%:1,33;7,80) con relación al grupo control. Hubo un incremento en la relevancia de las notificaciones con aumento de las reacciones adversas graves en cerca de cuatro veces (RR=3,87; IC95%:1,29;11,61) e inesperadas en cinco veces (RR=5,02; IC 95%: 1,33;18,93), con relación al grupo control. CONCLUSIONES: Las intervenciones educativas aumentan significativamente, en hasta cuatro meses, la cantidad y la relevancia de las notificaciones espontáneas de reacciones adversas a medicamentos por parte de los farmacéuticos de la región Norte de Portugal.OBJECTIVE: To evaluate the results of an intervention to improve the number and relevance of reports of adverse drug reactions. METHODS: A cluster-randomized controlled trial was conducted with pharmacists working in Northern Portugal, in 2007. After randomization, 364 individuals were placed into the intervention group (261 in telephone interviews and 103 in workshops), while the control group was comprised of 1,103 pharmacists. The following were approached in the educational intervention: the problem of adverse drug reaction, the impact on public health and spontaneous reporting. With regard to relevance, adverse reactions were classified into severe and unexpected. Statistical analysis was performed, based on the intention-to-treat principle; generalized linear mixed models were applied, using the penalized quasi-likelihood method. The pharmacists studied were followed during a period of 20 months. RESULTS: The intervention increased the rate of spontaneous reporting of adverse reactions three times (RR = 3.22; 95% CI 1.33;7.80), when compared to the control group. The relevance of reporting rose, with an increase in severe adverse reactions by approximately four times (RR = 3.87; 95% CI 1.29;11.61) and in unexpected adverse reactions by five times (RR = 5.02; 95% CI 1.33;18.93), compared to the control group. CONCLUSIONS: During a period of up to four months, educational interventions significantly increased the number and relevance of spontaneous reporting of adverse drug reactions by pharmacists in Northern Portugal.

ABSTRACT OBJECTIVE To describe different approaches to promote adverse drug reaction reporting among health care professionals, determining their cost-effectiveness. METHODS We analyzed and compared several approaches taken by the Northern Pharmacovigilance Centre (Portugal) to promote adverse drug reaction reporting. Approaches were compared regarding the number and relevance of adverse drug reaction reports obtained and costs involved. Costs by report were estimated by adding the initial costs and the running costs of each intervention. These costs were divided by the number of reports obtained with each intervention, to assess its cost-effectiveness. RESULTS All the approaches seem to have increased the number of adverse drug reaction reports. We noted the biggest increase with protocols (321 reports, costing 1.96 € each), followed by first educational approach (265 reports, 20.31 €/report) and by the hyperlink approach (136 reports, 15.59 €/report). Regarding the severity of adverse drug reactions, protocols were the most efficient approach, costing 2.29 €/report, followed by hyperlinks (30.28 €/report, having no running costs). Concerning unexpected adverse drug reactions, the best result was obtained with protocols (5.12 €/report), followed by first educational approach (38.79 €/report). CONCLUSIONS We recommend implementing protocols in other pharmacovigilance centers. They seem to be the most efficient intervention, allowing receiving adverse drug reactions reports at lower costs. The increase applied not only to the total number of reports, but also to the severity, unexpectedness and high degree of causality attributed to the adverse drug reactions. Still, hyperlinks have the advantage of not involving running costs, showing the second best performance in cost per adverse drug reactions report.

Introdução: Os profissionais de saúde foram um grupo prioritário para vacinação contra a pandemia da Gripe A (H1N1), Pandemrix®. Assim, monitorizar os eventos adversos relacionados com esta vacina neste grupo específico poderá originar informação valiosa relacionada com o perfil de segurança da vacina. O nosso objetivo foi identificar os eventos adversos após imunização com a vacina Pandemrix® em profissionais de saúde. Material e Métodos: Foi desenhado um questionário de monitorização dos eventos adversos ocorridos com a vacina Pandemrix®. O questionário foi distribuído aos profissionais de saúde a trabalhar em três centros hospitalares da região norte do País, vacinados no período de 26 de Outubro de 2009 a 31 de janeiro de 2009. Resultados: Dos 2358 profissionais de saúde que aceitaram participar no estudo, 864 (37%) devolveram o questionário preenchido. Destes, 73% experienciaram pelo menos um evento adverso após imunização, mas só 8% experienciaram um evento inesperado. Os eventos adversos mais frequentemente reportados foram os esperados e muito comuns: reações locais no local de administração (57%), mialgia (31%), fadiga (incluindo astenia) (24%) e dor de cabeça (19%). Não foram reportados casos de eventos de maior gravidade para a saúde, tais como morte ou risco de vida. O género feminino e a existência de doença de base foram fatores de risco independentes para o desenvolvimento de pelo menos um evento adverso após imunização com a Pandemrix®. Conclusões: O nosso trabalho sugere um perfil de segurança aceitável da vacina pandémica Pandermix® em profissionais de saúde. Tanto a frequência como a severidade dos eventos adversos não se verificaram superiores ao esperado.

O Sistema Nacional de Farmacovigilância (SNF) foi criado em 1992, completando durante o ano corrente 20 anos de existência. Tendo sido estabelecido de forma centralizada, depressa se tomou consciência que a sua descentralização geográfica traria vantagens ao nível da proximidade do Sistema aos profissionais de saúde, bem como do envolvimento das Universidades no mesmo. O SNF conta, atualmente, com quatro unidades regionais de farmacovigilância, que cobrem todo o território continental, e que se tornaram centros com vocação científica, levando a cabo alguns estudos farmacoepidemiológicos na área da segurança do medicamento. Além disso, são o garante da correta recolha, processamento e avaliação das notificações espontâneas de reações adversas a medicamentos (RAM), bem como da permanente divulgação do Sistema junto dos profissionais de saúde e promoção da notificação espontânea. Ao longo destes 20 anos, o SNF foi-se adaptando às exigências comunitárias na área da Farmacovigilância, sendo atualmente um sistema maduro e bem implementado, tendo como objetivos basilares a avaliação do perfil de segurança dos medicamentos comercializados e o desencadeamento de ações para reduzir os riscos da utilização desses medicamentos. A partir do 2º semestre de 2012, decorrerá uma nova adaptação, com a implementação da recente legislação europeia de farmacovigilância, publicada em dezembro de 2010. De entre outras alterações, destaca-se a possibilidade de os consumidores notificarem as suas suspeitas de RAM diretamente ao SNF (exclusiva, até agora, dos profissionais de saúde). Este trabalho pretende constituir uma reflexão sobre a evolução do Sistema Nacional de Farmacovigilância e a sua crescente importância na proteção da Saúde Pública.

Muscles must maintain cell compartmentalization when remodeled during development and use. How spatially restricted adhesions are regulated with muscle remodeling is largely unexplored. We show that the myotubularin (mtm) phosphoinositide phosphatase is required for integrin-mediated myofiber attachments in Drosophila melanogaster, and that mtm-depleted myofibers exhibit hallmarks of human XLMTM myopathy. Depletion of mtm leads to increased integrin turnover at the sarcolemma and an accumulation of integrin with PI(3)P on endosomal-related membrane inclusions, indicating a role for Mtm phosphatase activity in endocytic trafficking. The depletion of Class II, but not Class III, PI3-kinase rescued mtm-dependent defects, identifying an important pathway that regulates integrin recycling. Importantly, similar integrin localization defects found in human XLMTM myofibers signify conserved MTM1 function in muscle membrane trafficking. Our results indicate that regulation of distinct phosphoinositide pools plays a central role in maintaining cell compartmentalization and attachments during muscle remodeling, and they suggest involvement of Class II PI3-kinase in MTM-related disease.

BACKGROUND: The heart forms from a linear tube that is subject to complex remodeling during embryonic development. Hallmarks of this remodeling are the looping of the heart tube and the regionalization into chamber and non-chamber myocardium. Cardiomyocytes in the future chamber myocardium acquire different cellular and physiological characteristics through activation of a chamber-specific genetic program, which is in part mediated by T-box genes. METHODOLOGY/PRINCIPAL FINDING: We characterize two new zebrafish T-box transcription factors, tbx3b and tbx2a, and analyze their role during the development of the atrioventricular canal. Loss- and gain-of-function analyses demonstrate that tbx3b and tbx2a are necessary to repress the chamber-genetic program in the non-chamber myocardium. We also show that tbx3b and tbx2a are required to control cell proliferation in the atrioventricular canal and that misregulation of cell proliferation in the heart tube influences looping. Furthermore, we characterize the heart phenotype of a novel Tbx3 mutation in mice and show that both the control of cell proliferation and the repression of chamber-specific genetic program in the non-chamber myocardium are conserved roles of Tbx3 in this species. CONCLUSIONS/SIGNIFICANCE: Taken together, our results uncover an evolutionarily conserved role of Tbx2/3 transcription factors during remodeling of the heart myocardium and highlight the importance of controlling cell proliferation as a driving force of morphogenesis.