Spatial Analysis of Determinants of COVID-19 Vaccine Hesitancy in Portugal.

Vaccine hesitancy tends to exhibit geographical patterns and is often associated with social deprivation and migrant status. We aimed to estimate COVID-19 vaccination hesitancy in a high-vaccination-acceptance country, Portugal, and determine its association with sociodemographic risk factors. We used the Registry of National Health System Users to determine the eligible population and the Vaccination Registry to determine individuals without COVID-19 vaccine doses. Individuals older than five with no COVID-19 vaccine dose administered by 31 March 2022 were considered hesitant. We calculated hesitancy rates by municipality, gender, and age group for all municipalities in mainland Portugal. We used the spatial statistical scan method to identify spatial clusters and the Besag, Yorke, and Mollié (BYM) model to estimate the effect of age, gender, social deprivation, and migrant proportion across all mainland municipalities. The eligible population was 9,852,283, with 1,212,565 (12%) COVID-19 vaccine-hesitant individuals. We found high-hesitancy spatial clusters in the Lisbon metropolitan area and the country's southwest. Our model showed that municipalities with higher proportions of migrants are associated with an increased relative risk (RR) of vaccine hesitancy (RR = 8.0; CI 95% 4.6; 14.0). Social deprivation and gender were not associated with vaccine hesitancy rates. We found COVID-19 vaccine hesitancy has a heterogeneous distribution across Portugal and has a strong association with the proportion of migrants per municipality.

Assessment of the Implementation of the International Health Regulations during the COVID-19 Pandemic: Portugal as a Case Study.

INTRODUCTION: The International Health Regulations (IHR) were developed to prepare countries to deal with public health emergencies. The spread of SARS-CoV-2 underlined the need for international coordination, although few attempts were made to evaluate the integrated implementation of the IHR's core capacities in response to the COVID-19 pandemic. The aim of this study was to evaluate whether IHR shortcomings stem from non-compliance or regulatory issues, using Portugal as a European case study due to its size, organization, and previous discrepancies between self-reporting and peer assessment of the IHR's core capacities. METHODS: Fifteen public health medical residents involved in contact tracing in mainland Portugal interpreted the effectiveness of the IHR's core capabilities by reviewing the publicly available evidence and reflecting on their own field experience, then grading each core capability according to the IHR Monitoring Framework. The assessment of IHR enforcement considered efforts made before and after the onset of the pandemic, covering the period up to July 2021. RESULTS: Four out of nine core IHR capacities (surveillance; response; risk communication; and human resource capacity) were classified as level 1, the lowest. Only two were graded level 3 (preparedness; and laboratory), the highest. The remaining three) (national legislation, policy & financing; coordination and national focal point communication; and points of entry) were classified as level 2. CONCLUSION: Portugal exemplifies the extent to which implementation of the IHR was not fully achieved, which has resulted in the underperformance of several core capacities. There is a need to improve preparedness and international cooperation in order to harmonize and strengthen the global response to public health emergencies, with better political, institutional, and financial support.

The role of intrasexual competition on the evolution of male-male courtship display: a systematic review.

Background: Evidence of male-male courtship display is widespread across the animal kingdom. Yet, its function and evolutionary origin remain unclear. Here, we hypothesise that male-male courtship display evolved in response to selection pressure exerted by intrasexual competition during male-female courtship interactions. Intrasexual competition can be caused by bystander male pressure through eavesdropping and exploiting on displayer male's courtship interactions with females. This bystander pressure can lead to an audience effect by the displayer, who will change their courtship behaviour in the presence of bystanders and display directly towards them, even in the absence of females, as an intimidation strategy. In species where this selection pressure has taken place, we predict that the male courtship display will have a dual function: attract females and deter competitors. Therefore, we expected to find more evidence of bystander-related behaviours in species for which male-male courtship display is linked to intrasexual competition compared to species for which other explanatory hypotheses are more plausible (e.g., mistaken identity or courtship practice). Methodology: We conducted two systematic reviews to test this hypothesis. First, we conducted a search for studies of species with courtship display between males and of the hypotheses provided to explain this behaviour. Our goal was to identify the species with male-male courtship display and evidence of intrasexual competition. Second, among the species with male-male courtship display, we searched for evidence of bystander-related behaviours, i.e., articles referring to eavesdropping, exploitation, and audience effect during male-female courtship interactions. Our goal was to test whether species with intrasexual competition are also more likely to show bystander-related behaviours. Results: Although most studies reporting male courtship display towards other males do not suggest any explanatory hypothesis for this behaviour, the intrasexual competition hypothesis was largely mentioned and supported by some studies reviewed. Additionally, there is more evidence of eavesdropping and of all three bystander-related behaviours combined in species for which the intrasexual competition hypothesis was suggested. Conclusions: Overall, our review supports the hypothesis that intrasexual competition can play a key role in male courtship display evolution, namely that male-male courtship display may have evolved as a secondary function of male-female courtship interactions via bystander male pressure. However, our review also shows that despite the increasing interest in same-sex sexual behaviours, and male-male courtship display in particular, most studies were found to be merely descriptive, and the hypotheses they suggested to explain courtship display between males mostly speculative. This highlights an important gap in the literature. To clarify both the evolution and the function of male-male courtship display, this behaviour needs to be empirically studied more often. Our review can help advancing this research area, as it makes the 20 species with male-male courtship display for which the intrasexual competition hypothesis was suggested excellent candidates for empirical research.

Real-Time Classification of Causes of Death Using AI: Sensitivity Analysis.

BACKGROUND: In 2021, the European Union reported >270,000 excess deaths, including >16,000 in Portugal. The Portuguese Directorate-General of Health developed a deep neural network, AUTOCOD, which determines the primary causes of death by analyzing the free text of physicians' death certificates (DCs). Although AUTOCOD's performance has been established, it remains unclear whether its performance remains consistent over time, particularly during periods of excess mortality. OBJECTIVE: This study aims to assess the sensitivity and other performance metrics of AUTOCOD in classifying underlying causes of death compared with manual coding to identify specific causes of death during periods of excess mortality. METHODS: We included all DCs between 2016 and 2019. AUTOCOD's performance was evaluated by calculating various performance metrics, such as sensitivity, specificity, positive predictive value (PPV), and F1-score, using a confusion matrix. This compared International Statistical Classification of Diseases and Health-Related Problems, 10th Revision (ICD-10), classifications of DCs by AUTOCOD with those by human coders at the Directorate-General of Health (gold standard). Subsequently, we compared periods without excess mortality with periods of excess, severe, and extreme excess mortality. We defined excess mortality as 2 consecutive days with a Z score above the 95% baseline limit, severe excess mortality as 2 consecutive days with a Z score >4 SDs, and extreme excess mortality as 2 consecutive days with a Z score >6 SDs. Finally, we repeated the analyses for the 3 most common ICD-10 chapters focusing on block-level classification. RESULTS: We analyzed a large data set comprising 330,098 DCs classified by both human coders and AUTOCOD. AUTOCOD demonstrated high sensitivity (≥0.75) for 10 ICD-10 chapters examined, with values surpassing 0.90 for the more prevalent chapters (chapter II-"Neoplasms," chapter IX-"Diseases of the circulatory system," and chapter X-"Diseases of the respiratory system"), accounting for 67.69% (223,459/330,098) of all human-coded causes of death. No substantial differences were observed in these high-sensitivity values when comparing periods without excess mortality with periods of excess, severe, and extreme excess mortality. The same holds for specificity, which exceeded 0.96 for all chapters examined, and for PPV, which surpassed 0.75 in 9 chapters, including the more prevalent ones. When considering block classification within the 3 most common ICD-10 chapters, AUTOCOD maintained a high performance, demonstrating high sensitivity (≥0.75) for 13 ICD-10 blocks, high PPV for 9 blocks, and specificity of >0.98 in all blocks, with no significant differences between periods without excess mortality and those with excess mortality. CONCLUSIONS: Our findings indicate that, during periods of excess and extreme excess mortality, AUTOCOD's performance remains unaffected by potential text quality degradation because of pressure on health services. Consequently, AUTOCOD can be dependably used for real-time cause-specific mortality surveillance even in extreme excess mortality situations.

The forced swim test has poor accuracy for identifying novel antidepressants.

Despite the prevalence of treatment-resistant depression, many pharmaceutical companies have abandoned the development of new antidepressants. Experts have attributed this, in part, to the low quality of preclinical tests available in this field, often citing over-reliance on animal behavioral screens, such as the forced swim test (FST). This retrospective review assessed whether compounds tested in the FST by major pharmaceutical companies were shown to have antidepressant effects in humans. Of 109 compounds identified, only 28% had been explored for antidepressant effects in humans. Of these, there were only three for which the FST appeared to positively predict antidepressant efficacy, but none are currently approved to treat any type of depression. With such poor accuracy for identifying novel antidepressants, the FST might not be a useful screening tool for this purpose.

The Contribution of Rat Studies to Current Knowledge of Major Depressive Disorder: Results From Citation Analysis.

Major depressive disorder (MDD) is the most severe depression type and one of the leading causes of morbidity worldwide. Animal models are widely used to understand MDD etiology, pathogenesis, and treatment, but the efficacy of this research for patients has barely been systematically evaluated. Such evaluation is important given the resource consumption and ethical concerns incurred by animal use. We used the citation tracking facilities within Web of Science and Scopus to locate citations of original research papers on rats related to MDD published prior to 2013-to allow adequate time for citations-identified in PubMed and Scopus by relevant search terms. Resulting citations were thematically coded in eight categories, and descriptive statistics were calculated. 178 publications describing relevant rat studies were identified. They were cited 8,712 times. More than half (4,633) of their citations were by other animal studies. 794 (less than 10%) were by human medical papers. Citation analysis indicates that rat model research has contributed very little to the contemporary clinical understanding of MDD. This suggests a misuse of limited funding hence supporting a change in allocation of research and development funds targeting this disorder to maximise benefits for patients.

Are in vitro and in silico approaches used appropriately for animal-based major depressive disorder research?

The current paradigm for biomedical research and drug testing postulates that in vitro and in silico data inform animal studies that will subsequently inform human studies. Recent evidence points out that animal studies have made a poor contribution to current knowledge of Major Depressive Disorder, whereas the contribution of in vitro and in silico studies to animal studies- within this research area- is yet to be properly quantified. This quantification is important since biomedical research and drug discovery and development includes two steps of knowledge transferability and we need to evaluate the effectiveness of both in order to properly implement 3R principles (Replacement, Reduction and Refinement). Here, we used the citation tracking facility within Web of Science to locate citations of original research papers on in vitro and in silico related to MDD published identified in PubMed by relevant search terms. 67 publications describing target papers were located. Both in vitro and in silico papers are more cited by human medical papers than by animal papers. The results suggest that, at least concerning MDD research, the current two steps of knowledge transferability are not being followed, indicating a poor compliance with the 3R principles.

The Relevance of In Silico, In Vitro and Non-human Primate Based Approaches to Clinical Research on Major Depressive Disorder.

Major depressive disorder (MDD) is the most severe form of depression and the leading cause of disability worldwide. When considering research approaches aimed at understanding MDD, it is important that their effectiveness is evaluated. Here, we assessed the effectiveness of original studies on MDD by rating their contributions to subsequent medical papers on the subject, and we compared the respective contribution of findings from non-human primate (NHP) studies and from human-based in vitro or in silico research approaches. For each publication, we conducted a quantitative citation analysis and a systematic qualitative analysis of the citations. In the majority of cases, human-based research approaches (both in silico and in vitro) received more citations in subsequent human research papers than did NHP studies. In addition, the human-based approaches were considered to be more relevant to the hypotheses and/or to the methods featured in the citing papers. The results of this study suggest that studies based on in silico and in vitro approaches are taken into account by medical researchers more often than are NHP-based approaches. In addition, these human-based approaches are usually cheaper and less ethically contentious than NHP studies. Therefore, we suggest that the traditional animal-based approach for testing medical hypotheses should be revised, and more opportunities created for further developing human-relevant innovative techniques.

Ethical and Scientific Pitfalls Concerning Laboratory Research with Non-Human Primates, and Possible Solutions.

Basic and applied laboratory research, whenever intrusive or invasive, presents substantial ethical challenges for ethical committees, be it with human beings or with non-human animals. In this paper we discuss the use of non-human primates (NHPs), mostly as animal models, in laboratory based research. We examine the two ethical frameworks that support current legislation and guidelines: deontology and utilitarianism. While human based research is regulated under deontological principles, guidelines for laboratory animal research rely on utilitarianism. We argue that the utilitarian framework is inadequate for this purpose: on the one hand, it is almost impossible to accurately predict the benefits of a study for all potential stakeholders; and on the other hand, harm inflicted on NHPs (and other animals) used in laboratory research is extensive despite the increasing efforts of ethics committees and the research community to address this. Although deontology and utilitarianism are both valid ethical frameworks, we advocate that a deontological approach is more suitable, since we arguably have moral duties to NHPs. We provide suggestions on how to ensure that research currently conducted in laboratory settings shifts towards approaches that abide by deontological principles. We assert that this would not impede reasonable scientific research.

[Study on Portuguese Medical Schools' Learning Conditions: A National Analysis on Student Satisfaction, Student-Tutor Ratios and Number of Admissions]. / Estudo sobre as Condições Pedagógicas das Escolas Médicas Portuguesas: Uma Análise Nacional Sobre a Satisfação Estudantil, Rácios Estudante-Tutor e Número de Admissões.

INTRODUCTION: Experiences of clinical and nonclinical learning environments, as well as assessment and study environments influence student satisfaction with their medical schools. Student-tutor ratios may impact on their perception of clinical learning environments. The aim of this study was to analyze medical students' satisfaction and student-tutor ratios in relation to medical schools' number of admissions. MATERIALS AND METHODS: A questionnaire was created, regarding learning, assessment and study environments in eight medical schools. 2037 students participated in this cross-sectional study. Cronbach' alpha (internal consistency) was calculated and principal component analysis was conducted. Pearson correlations and multiple comparisons were analyzed. RESULTS: Assessment environments showed the highest satisfaction scores and clinical learning environments the lowest scores. The national student-tutor ratio in clinical rotations is 7.53; there are significant differences among schools. Institutions with higher number of admissions showed the lowest scores of overall student satisfaction (r = -0.756; p < 0.05), which decreased with progression in the medical course. High student-tutor ratios are strongly correlated with low levels of satisfaction regarding clinical learning environments (r = -0.826; p < 0.05). DISCUSSION: Clinical learning environments show the lowest satisfaction scores, which may expose the effect of high ratios in clinical rotations. Depending on the number of admissions, significant differences between medical schools were found. Quality of teaching-learning strategies and articulation with hospitals might also be important variables. CONCLUSION: Medical schools with more admissions might be more susceptible to lower scores of student satisfaction. High student-tutor ratios in clinical rotations may reduce the quality of learning experiences and inhibit the acquisition of competences.

Introdução: Os ambientes de ensino clínico e não clínico, bem como as condições de avaliação e estudo, influenciam a satisfação estudantil com as Escolas Médicas. Os rácios estudante-tutor podem ter impacto na perceção sobre o ensino em meio clínico. Este estudo tem como objetivo analisar a satisfação dos estudantes de Medicina e os rácios estudante-tutor em relação com o número de admissões das Escolas Médicas. Materiais e Métodos: Foi criado um questionário sobre os ambientes de aprendizagem, avaliação e estudo em oito Escolas Médicas, distribuído a 2037 estudantes. Calculou-se o alfa de Cronbach (consistência interna) e executou-se uma análise de componentes principais. Resultados: Condições de avaliação obtiveram os melhores resultados de satisfação, enquanto o ensino em meio clínico revelou as menores pontuações. O rácio estudante-tutor nacional em disciplinas clínicas (7,53) traduz diferenças significativas entre Escolas. Instituições com maior número de admissões evidenciam resultados inferiores de satisfação estudantil (r= -0,756; p < 0,05), com redução progressiva ao longo do curso. Elevados rácios estão correlacionados com baixa satisfação com o ensino em meio clínico (r= -0,826; p < 0,05). Discussão: O ensino em meio clínico evidencia menor satisfação estudantil, traduzindo os elevados rácios em disciplinas clínicas. Dependendo do número de admissões, existem diferenças significativas entre Escolas. A qualidade das estratégias de ensino-aprendizagem e articulação hospitalar podem igualmente ser variáveis importantes. Conclusão: As Escolas com maior número de admissões podem ser mais suscetíveis a baixos resultados de satisfação estudantil. Elevados rácios estudante-tutor em disciplinas clínicas podem reduzir a qualidade do ensino em meio clínico e inibir a aquisição de competências.

Contribution of animal models to contemporary understanding of Attention Deficit Hyperactivity Disorder.

Attention Deficit Hyperactivity Disorder (ADHD) is a poorly understood neurodevelopmental disorder of multifactorial origin. Animal-based research has been used to investigate ADHD aetiology, pathogenesis and treatment, but the efficacy of this research for patients has not yet been systematically evaluated. However, such evaluation is important, given the resource consumption and ethical concerns incurred by animal use. Accordingly, we used the citation tracking facility within Web of Science to locate original research performed on animal models related to ADHD, prior to 2010. Human medical papers citing those animal studies were carefully analyzed by two independent raters to evaluate the contribution of the animal to the human studies. 211 publications describing relevant animal studies were located. Approximately half (3,342) of their 6,406 citations were by other animal studies. 446 human medical papers cited 121 of these 211 animal studies, a total of 500 times. 254 of these 446 papers were human studies of ADHD. However, only eight animal papers (cited 10 times) were relevant to the hypothesis of the human medical study in question. Three of these eight papers described results from both human and animal studies, but their citations solely referred to the human data. Five animal research papers were relevant to the hypotheses of the applicable human medical papers. Citation analysis indicates that animal research has contributed very little to contemporary understanding of ADHD. To ensure optimal allocation of Research & Development funds targeting this disease the contribution of other research methods should be similarly evaluated.