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A OMA (Otite Média Aguda) é dos diagnósticos mais efetuados em idade pediátrica, afetando todas as faixas etárias, e a grande maioria das crianças até aos 5 anos já teve pelo menos um episódio. A imaturidade do sistema imunitário e a anatomia em desenvolvimento da trompa de Eustáquio levam ao grande número de OMA diagnosticada nesta população. Apesar de ser das patologias mais comuns na infância, especialmente nos 2 primeiros anos de vida, é uma entidade rara e pouco discutida abaixo dos 3 meses de idade e o seu diagnóstico pode ser particularmente difícil neste grupo etário. O curso da doença é habitualmente auto-limitado e benigno, mas o seu tratamento tem sido alvo de constante investigação e atualização, estando hoje em dia preconizada uma estratégia mais contida do uso de AB, uma vez que esta terapêutica terá um impacto limitado no curso da doença, principalmente em crianças acima dos 2 anos de vida. No presente trabalho pretende-se rever a anatomia do ouvido do recém-nascido e lactente, rever a fisiopatologia da OMA e abordar quais as melhores estratégias diagnósticas e terapêuticas.

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Esta Newsletter (NL) resulta de uma parceria entre o Instituto de Saúde Baseada na Evidência e a Cochrane Portugal, e tem como objectivo disponibilizar informação sobre áreas interessantes para a prática clínica, com base na melhor evidência científica. São incluídos estudos relevantes, criticamente avaliados pela sua validade, importância dos resultados e aplicabilidade prática, resumidos numa óptica de suporte à decisão. É dada prioridade a estudos de causalidade incluindo-se ainda, quando justificado, estudos qualitativos e metodológicos, assim como revisões científicas. O conteúdo da NL é da exclusiva responsabilidade do(s) seu(s) autor(es).

Introduction: Criticisms have been raised against the sole use of p-value in interpreting results from randomized controlled trials (RCTs). Additional tools have been suggested, like the fragility index (FI), a measure of a trial’s robustness/fragility, and derivative measures. The FI is the minimum number of patients who would have to be converted from nonevents to events, in the group with the least events, for a result to lose statistical significance. Objective: This study aimed to evaluate RCT supporting European Society of Cardiology (ESC) guidelines regarding antithrombotics, using the FI and FI-related measures. Methods FI, fragility quotient (FQ), and FI minus LTF lost to follow-up (FI LTF) were calculated for the RCT underpinning recommendations regarding antithrombotic therapy from the updated ESC guidelines. LTF was compared with FI. Results were calculated for the total group of studies, as per guideline and as per recommendation type. Results Overall, 61 studies were included. The median FI was 24.5 (interquartile range [IQR]: 9.0–60.0) and median FQ was 0.0035 (IQR: 0.0019–0.0056). Median FI LTF was 2.0 (IQR: 0.0–38.0). Twenty (32.8%) of the studies had one primary or main safety outcome with LTF exceeding FI. Peripheral arterial disease guideline and chronic coronary syndrome guideline had the lowest (2.5; IQR: 1.8–3.3) and the highest (48.5; IQR: 23.8–73.0) FI, respectively. Conclusion: The median FI suggests robustness of clinical trials evaluating antithrombotic drugs cited in the guidelines, but about one-third of them had LTF larger than FI. This emphasizes the need for assessing trials’ robustness when constructing guidelines.

Preventive cardiology encompasses the whole spectrum of cardiovascular disease (CVD) prevention, at individual and population level, through all stages of life. This includes promotion of cardiovascular (CV) health, management of individuals at risk of developing CVD, and management of patients with established CVD, through interdisciplinary care in different settings. Preventive cardiology addresses all aspects of CV health in the context of the social determinants of health, including physical activity, exercise, sports, nutrition, weight management, smoking cessation, psychosocial factors and behavioural change, environmental, genetic and biological risk factors, and CV protective medications. This is the first European Core Curriculum for Preventive Cardiology, which will help to standardize, structure, deliver, and evaluate training in preventive cardiology across Europe. It will be the basis for dedicated fellowship programmes and a European Society of Preventive Cardiology (EAPC) subspecialty certification for cardiologists, with the intention to improve quality and outcome in CVD prevention.

Objective: To investigate the prognostic value of left atrial volume index (LAVI) in patients with moderate to severe aortic regurgitation (AR) and bicuspid aortic valve (BAV). Methods: 554 individuals (45 (IQR 33-57) years, 80% male) with BAV and moderate or severe AR were selected from an international, multicentre registry. The association between LAVI and the combined endpoint of all-cause mortality or aortic valve surgery was investigated with Cox proportional hazard regression analyses. Results: Dilated LAVI was observed in 181 (32.7%) patients. The mean indexed aortic annulus, sinus of Valsalva, sinotubular junction and ascending aorta diameters were 13.0±2.0 mm/m2, 19.4±3.7 mm/m2, 16.5±3.8 mm/m2 and 20.4±4.5 mm/m2, respectively. After a median follow-up of 23 (4-82) months, 272 patients underwent aortic valve surgery (89%) or died (11%). When compared with patients with normal LAVI (<35 mL/m2), those with a dilated LAVI (≥35 mL/m2) had significantly higher rates of aortic valve surgery or mortality (43% and 60% vs 23% and 36%, at 1 and 5 years of follow-up, respectively, p<0.001). Dilated LAVI was independently associated with reduced event-free survival (HR=1.450, 95% CI 1.085 to 1.938, p=0.012) after adjustment for LV ejection fraction, aortic root diameter, LV end-diastolic diameter and LV end-systolic diameter. Conclusions: In this large, multicentre registry of patients with BAV and moderate to severe AR, left atrial dilation was independently associated with reduced event-free survival. The role of this parameter for the risk stratification of individuals with significant AR merits further investigation.

O presente estudo tem como objetivo analisar a relação entre a Perceção de Suporte Organizacional (POS) e o Compromisso Organizacional tendo como foco a vertente Afetiva (CA) do mesmo. Além disso, também foi testado o papel moderador do excesso de trabalho na relação entre a POS e o CA. Os dados foram obtidos através da resposta a um questionário por parte dos trabalhadores de uma organização do setor industrial (N=400). Os resultados suportam a existência de uma relação significativa e positiva entre a Perceção de Suporte Organizacional e o Compromisso Organizacional Afetivo. No entanto, a hipótese relativa à moderação do excesso de trabalho nesta relação foi refutada. Contudo, as conclusões retiradas do presente estudo apresentam implicações práticas para a Gestão de Recursos Humanos, salientando o papel que o suporte organizacional tem no bem-estar dos trabalhadores e no cumprimento dos objetivos organizacionais. Por fim, ainda são apresentadas algumas limitações e sugestões para estudos futuros.

We compared the impact of a one-year periodized exercise training versus a non-periodized exercise training on health-related physical fitness (HRPF) including body composition, cardiorespiratory and muscular fitness in patients with coronary artery disease (CAD). Fifty CAD patients (60.4 ± 9.9 years) were randomized to either a periodized training group (PG) (n = 25) or a non-periodized training group (NPG) (n = 25). Both consisted of a combined training programme, performed 3 days/week for 12 months. Thirty-six CAD patients (PG: n = 18, NPG: n = 18) successfully completed the exercise regimes. In both groups, a favourable main effect for time was evident for peak VO2, peak workload, anaerobic threshold and respiratory compensation point workloads and VO2, whole body skeletal muscle mass and quality index at 12 months.In conclusion, a periodized model is as effective as a non-periodized model in promoting increases in HRPF outcomes following a one-year intervention. These findings indicate that health-professionals can add variation to cardiac rehabilitation workouts without compromising effectiveness.

This study aims to understand the cause of the recent observation that humans with a higher diversity of virulence genes in their metagenomes tend to be precisely those with higher diversity of antibiotic-resistance genes. We simulated the transferring of virulence and antibiotic-resistance genes in a community of interacting people where some take antibiotics. The diversities of the two genes types became positively correlated whenever the contagion probability between two people was higher than the probability of losing resistant genes. However, no such positive correlations arise if no one takes antibiotics. This finding holds even under changes of several simulations’ parameters, such as the relative or total diversity of virulence and resistance genes, the contagion probability between individuals, the loss rate of resistance genes, or the social network type. Because the loss rate of resistance genes may be shallow, we conclude that the contagion between people and antibiotic usage is the leading cause of establishing the positive correlation mentioned above. Therefore, antibiotic use and something as prosaic as the contagion between people may facilitate the emergence of virulent and multi-resistant bacteria in people’s metagenomes with a high diversity of both gene types. These superbugs may then circulate in the community.

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Persistence is a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Given its obvious advantage to bacteria, several researchers have been looking for the genetic mechanism behind persistence. However, other authors argue that there is no such mechanism and that persistence results from inadvertent cell errors. In this case, the persistent population should decay according to a power-law with a particular exponent of −2. Studying persisters’ decay is, therefore, a valuable way to understand persistence. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance. Eventually, under indirect resistance, detoxifying drug-resistant cells save the persister cells that leave the dormant state and resume growth. The simulations presented here show that, by assuming a power-law decline, the exponent is close to −2, which is the expected value if persistence results from unintentional errors. Whether persisters are cells in a moribund state or, on the contrary, result from a genetic program, should impact the research of anti-persistent drugs.

Recently, much attention has been paid to the COVID-19 pandemic, yet bacterial resistance to antibiotics remains a serious and unsolved public health problem, which kills thousands of people annually, being an insidious and silent pandemic. In this study, we explored the idea of confinement and the tightening of the hygiene measures to contain the spreading of coronavirus, to simulate the effect that it has on lowering the spreading of pathogenic bacteria in a human network, and on the need to use antibiotics. For that, we used computational biology to generate simulations

O presente projecto inclui-se no projecto de construção de um pacing diafragmático fisiológico e dinâmico, implantável no diafragma. O objectivo específico deste trabalho consiste na monitorização, em modelo animal, de variações da actividade do frénico, variando a frequência de ciclos respiratórios através de respiração artificial de ar ambiente enriquecido em O2. Estes resultados possibilitarão a construção de um pacing respiratório dinâmico que mimetisa, de forma artificial, o quimiorreflexo humano, responsável pela regulação da respiração.

Evolution is a key concept of biology, fundamental to understand the world and address important societal problems, but research studies show that it is still not widely understood and accepted. Several factors are known to influence evolution acceptance and understanding, but little information is available regarding the impacts of the curriculum on these aspects. Very few curricula have been examined to assess the coverage of biological evolution. The available studies do not allow comparative analyses, due to the different methodologies employed by the authors. However, such an analysis would be useful for research purposes and for the development of appropriate educational policies to address the problem of a lack of evolution acceptance in some countries. In this paper we describe the steps through which we developed a valid and reliable instrument for curricula analysis known as FACE: “Framework to Assess the Coverage of biological Evolution by school curricula.” This framework was developed based on the “Understanding Evolution Conceptual Framework” (UECF). After an initial pilot study, our framework was reformulated based on identified issues and experts’ opinions. To generate validity and reliability evidence in support of the framework, it was applied to four European countries’ curricula. For each country, a team of a minimum of two national and two foreign coders worked independently to assess the curriculum using this framework for content analysis. Reliability evidence was estimated using Krippendorf's alpha and resulted in appropriate values for coding the examined curricula. Some issues that coders faced during the analysis were discussed and, to ensure better reliability for future researchers, additional guidelines and one extra category were included in the framework. The final version of the framework includes six categories and 34 subcategories. FACE is a useful tool for the analysis and the comparison of curricula and school textbooks regarding the coverage of evolution, and such results can guide curricula development.

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Introduction: Sudden and unexpected postnatal collapse is a rare event with potentially dramatic consequences. Intervention approaches are limited, but hypothermia has been considered after postnatal collapse. The aim of this study was to analyse sudden and unexpected postnatal collapse cases that underwent therapeutic hypothermia in the five Portuguese hypothermia centres. Material and Methods: In this multicentre, retrospective and descriptive study, clinical, ultrasonography, amplitude-integrated electroencephalography and brain magnetic resonance findings of newborns with postnatal collapse that underwent therapeutic hypothermia are reported (2010 - 2018). Statistical analysis was performed by using IBM SPSS Statistics version 21. Results: Twenty-two cases of sudden and unexpected postnatal collapse were referred for therapeutic hypothermia (82% outborn), all ≥ 36 weeks, with Apgar 5´ ≥ 8. Collapse occurred during the first two hours in 73% (all < 24 hours), 50% during skin-to-skin care, 55% related to feeding and 23% during co-bedding. Moderate-severe encephalopathy and severe acidosis were observed (median: Thompson score 16, pH 6.90, base deficit 22 mmol/L). Amplitude-integrated electroencephalogram was abnormal in 95% and magnetic resonance imaging showed severe brain injury in 46%. The mortality rate was 50%. A possible cause was identified in 27%. Discussion: The incidence rate of 2.7 sudden cases of postnatal collapse per 100 000 births, is possibly under-estimated. All infants suffered the collapse in the first day, mostly within the first two hours, as reported before. Possible causes were identified in less than a third of cases, but multiple predisposing conditions were identified, suggesting that prevention may be possible. Newborn positioning and skin-to-skin care have been the most discussed practices. A significant proportion of infants had poor outcomes. Lower Thompson score, electroencephalogram amplitude normalization and normal magnetic resonance imaging seemed to indicate better outcomes. Although conclusive trials on therapeutic hypothermia after postnatal collapse are not available, its use has been considered individually. No severe adverse effects directly related to hypothermia were registered in this study, but the results do not allow drawing meaningful conclusions. Conclusion: In our national sample of 22 infants who suffered sudden and unexpected postnatal collapse and underwent therapeutic hypothermia, a significant proportion had poor outcomes. Absolute conclusions from our experience with hypothermia in postnatal collapse cannot be drawn, but systematic reporting of cases and long-term clinical evaluation would facilitate understanding of the real benefits of hypothermia. As this procedure has not been validated with clinical trials for this indication, its use should be considered on a case-by-case approach. The potentially avoidable nature of unexpected postnatal collapse is evident from its association with certain behaviours and risk factors. Surveillance practices during the first hours should be implemented, whilst the benefits of breastfeeding and skin-to-skin care should continue to be widely promoted.

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Aims: Here we explore the presence of mediator complex subunit 12 (MED12) exon 2 and telomerase reverse transcriptase (TERT) promoter hotspot mutations in complex fibroadenomas (CFAs) of the breast. Methods: The stromal components from 18 CFAs were subjected to Sanger sequencing of MED12 exon 2 and the TERT promoter hotspot loci. The epithelial and stromal components of two MED12 mutated CFAs were subjected to laser capture microdissection, and Sanger sequencing of MED12 exon 2, TERT promoter and PIK3CA exons 9 and 20, separately. Results: MED12 exon 2 mutations were identified in the stroma of 17% of CFAs. The analyses of epithelial and stromal components, microdissected separately, revealed that MED12 mutations were restricted to the stroma. No TERT promoter or PIK3CA mutations in exons 9 and 20 were detected in analysed CFAs. Conclusions: Like conventional fibroadenomas, MED12 exon 2 mutations appear to be restricted to the stromal component of CFAs, supporting the notion that CFAs are stromal neoplasms.