Craniofacial syndromes and class III phenotype: common genotype fingerprints? A scoping review and meta-analysis.

Skeletal Class III (SCIII) is among the most challenging craniofacial dysmorphologies to treat. There is, however, a knowledge gap regarding which syndromes share this clinical phenotype. The aims of this study were to: (i) identify the syndromes affected by the SCIII phenotype; (ii) clarify the involvement of maxillary and/or mandibular structures; (iii) explore shared genetic/molecular mechanisms. A two-step strategy was designed: [Step#1] OMIM, MHDD, HPO, GeneReviews and MedGen databases were explored; [Step#2]: Syndromic conditions indexed in [Step#1] were explored in Medline, Pubmed, Scopus, Cochrane Library, WOS and OpenGrey. Eligibility criteria were defined. Individual studies were assessed for risk of bias using the New Ottawa Scale. For quantitative analysis, a meta-analysis was conducted. This scoping review is a hypothesis-generating research. Twenty-two studies met the eligibility criteria. Eight syndromes affected by the SCIII were targeted: Apert syndrome, Crouzon syndrome, achondroplasia, X-linked hypohidrotic ectodermal dysplasia (XLED), tricho-dento-osseous syndrome, cleidocranial dysplasia, Klinefelter and Down syndromes. Despite heterogeneity between studies [p < 0.05], overall effects showed that midface components were affected in Apert and Down Syndromes, lower face in Klinefelter Syndrome and midface and lower face components in XLED. Our review provides new evidence on the craniofacial characteristics of genetically confirmed syndromes exhibiting the SCIII phenotype. Four major regulatory pathways might have a modulatory effect on this phenotype. IMPACT: What does this review add to the existing literature? To date, there is no literature exploring which particular syndromes exhibit mandibular prognathism as a common trait. Through this research, it was possibly to identify the particular syndromes that share the skeletal Class III phenotype (mandibular prognathism) as a common trait highlighting the common genetic and molecular pathways between different syndromes acknowledging their impact in craniofacial development.

Expert perspectives on strategic factors for the management and prevention of heart failure in Portugal.

INTRODUCTION AND OBJECTIVES: Heart failure (HF) has significant morbidity and mortality, and its prevalence will continue to increase in the future. This unfavorable evolution requires reflection as well as recommendations and decisions based on expert critical and strategic appraisal. METHODS: In the Acceleration on Heart Failure Empowerment and Awareness - the Portuguese Challenge (ATHENA-PT) study, a range of strategic factors that represent the strengths, weaknesses, threats, and opportunities (SWOT) of HF in Portugal were established. These factors were assessed quantitatively by experts, to create a final SWOT matrix for the management and prevention of HF in Portugal and to outline recommendations. RESULTS: For HF management, the panel emphasized the following strategic recommendations: (i) reimbursement of natriuretic peptides testing in primary healthcare; (ii) reimbursement of Doppler assessment in echocardiographic studies and promotion of detailed information in reports; (iii) intervention to improve the prognosis of patients with HF with preserved ejection fraction; (iv) ensuring effective healthcare transition between hospital and ambulatory units, using checklists/protocols; and (v) reinforcement and commitment to the training of primary health physicians and to the cardiac rehabilitation of patients. For the prevention of HF, the following recommendations/proposals were proposed: (i) campaigns to raise awareness of cardiovascular disease risk factors; (ii) promotion of physical exercise and healthy eating; and (iii) avoidance of therapeutic inertia in the management of risk factors. CONCLUSIONS: The acknowledgment of various strategic factors and their prioritization by experts made it possible to create and reinforce a range of new strategic recommendations for the management and prevention of HF.

Atherosclerosis in the primary health care setting: A real-word data study.

INTRODUCTION AND OBJECTIVES: To characterize patients with atherosclerosis, a disease with a high socioeconomic impact, in the Lisbon and Tagus Valley Health Region. METHODS: A cross-sectional observational study was carried out through the Lisbon and Tagus Valley Regional Health Administration primary health care database, extracting data on the clinical and demographic characteristics and resource use of adult primary health care users with atherosclerosis during 2016. Different criteria were used to define atherosclerosis (presence of clinical manifestations, atherothrombotic risk factors and/or consumption of drugs related to atherosclerosis). Comparisons between different subpopulations were performed using parametric tests. RESULTS: A total of 318 692 users were identified, most of whom (n=224 845 users; 71%) had no recorded clinical manifestations. The subpopulation with clinical manifestations were older (72.0±11.5 vs. 71.3±11.0 years), with a higher proportion of men (58.0% vs. 45.9%), recorded hypertension (78.3% vs. 73.5%) and dyslipidemia (55.8% vs. 53.5%), and a lower proportion of recorded obesity (18.2% vs. 20.8%), compared to those without clinical manifestations (p<0.001). Mean blood pressure, LDL-C and glycated hemoglobin values were lower in the subpopulation with manifestations (142/74 vs. 146/76 mmHg, 101 vs. 108 mg/dl, and 6.80 vs. 6.84%, respectively; p<0.001). Each user with atherosclerosis attended 4.1±2.9 face-to-face medical consultations and underwent 8.6±10.0 laboratory test panels, with differences in subpopulations with and without clinical manifestations (4.4±3.2 vs. 4.0±2.8 and 8.3±10.3 vs. 8.7±9.8, respectively; p<0.001). CONCLUSIONS: About one in three adult primary health care users with atherosclerosis have clinical manifestations. The results suggest that control of cardiovascular risk factors is suboptimal in patients with atherosclerosis.

Broadening risk factor or disease definition as a driver for overdiagnosis: A narrative review.

Medical overuse-defined as the provision of health services for which potential harms exceed potential benefits-constitutes a paradigm of low-value care and is seen as a threat to the quality of care. Value in healthcare implies a precise definition of disease. However, defining a disease may not be straightforward since clinical data do not show discrete boundaries, calling for some clinical judgment. And, if in time a redefinition of disease is needed, it is important to recognize that it can induce overdiagnosis, the identification of medical conditions that would, otherwise, never cause any significant symptoms or lead to clinical harm. A classic example is the impact of recommendations from professional societies in the late 1990s, lowering the threshold for abnormal total cholesterol from 240 mg/dl to 200 mg/dl. Due to these changes in risk factor definition, literally overnight there were 42 million new cases eligible for treatment in the United States. The same happened with hypertension-using either the 2019 NICE guidelines or the 2018 ESC/ECC guidelines criteria for arterial hypertension, the proportion of people overdiagnosed with hypertension was calculated to be between 14% and 33%. In this review, we will start by discussing resource overuse. We then present the basis for disease definition and its conceptual problems. Finally, we will discuss the impact of changing risk factor/disease definitions in the prevalence of disease and its consequences in overdiagnosis and overtreatment (a problem particularly relevant when definitions are widened to include earlier or milder disease).

Lost in transition: a systematic review of the association between unemployment and mental health.

BACKGROUND: Unemployment can involve financial strain and major psychosocial challenges. Integration of the existing evidence is needed to better characterize the association between unemployment and mental health, independently of macroeconomic contexts. AIMS: Main objectives of this study: (a) review, integrate, and summarize evidence about the association between unemployment and anxiety disorders, mood disorders, and suicidal behaviour, and (b) identify variables affecting this association. METHOD: Systematic review of literature following PRISMA guidelines. PubMed, Web of Science, SciELO, RCAAP, and Cochrane Library databases were searched. Quantitative empirical studies on the association between unemployment and mental illness of community-based samples were included. The quality of the evidence provided in the studies was assessed following pre-defined methodological criteria. RESULTS: Overall, 294 articles were considered eligible. In total, 55.7% of the studies were conducted in Europe; 91.4% supported a positive association between increased unemployment rates and anxiety, mood disorders, or suicidal behavior. Men and young adults were most severely affected by unemployment. Education and social support were found to buffer the negative outcomes of job loss. CONCLUSIONS: Unemployment was inversely associated with mental health irrespectively of the economic context; unemployed individuals were more vulnerable to commit suicide and suffer from anxiety and mood disorders.

[The problem of overutilization of resources and the Choosing Wisely Portugal program - Judicious Choices in Health]. / O problema da sobreutilização de recursos e o projeto Choosing Wisely Portugal - Escolhas Criteriosas em Saúde.

The variation of clinical practice is a well-described phenomenon in which patients with similar diagnoses, prognoses and demographic status receive different levels of care depending on when, where and by whom they are treated, despite agreed and documented evidence of best practice. The overutilization of health resources is also known to have a negative risk-benefit ratio. Unfortunately, both phenomena occur in several countries, especially in developed countries. In the light of this, the American Board of Internal Medicine launched the Choosing Wisely campaign, which has subsequently been implemented in several countries, including Portugal.

A variação da prática clínica é um fenómeno que se encontra bem descrito e que se caracteriza por uma prática clínica utilizando testes diagnósticos e esquemas terapêuticos diversos, em doentes semelhantes na patologia que apresentam e no seu risco basal. A sobreutilização de recursos em saúde caracteriza-se por apresentar um benefício-risco negativo. Infelizmente ambos os fenómenos se verificam em diversos países, em particular países desenvolvidos. Neste contexto, o American Board of Internal Medicine lançou a campanha Choosing Wisely, a qual foi, entretanto, implementada em diversos países incluindo Portugal.

O problema da sobreutilização de recursos e o projeto Choosing Wisely Portugal - Escolhas Criteriosas em Saúde / The problem of overutilization of resources and the Choosing Wisely Portugal program - Judicious Choices in Health

Resumo A variação da prática clínica é um fenómeno que se encontra bem descrito e que se caracteriza por uma prática clínica utilizando testes diagnósticos e esquemas terapêuticos diversos, em doentes semelhantes na patologia que apresentam e no seu risco basal. A sobreutilização de recursos em saúde caracteriza-se por apresentar um benefício-risco negativo. Infelizmente ambos os fenómenos se verificam em diversos países, em particular países desenvolvidos. Neste contexto, o American Board of Internal Medicine lançou a campanha Choosing Wisely, a qual foi, entretanto, implementada em diversos países incluindo Portugal.

Abstract The variation of clinical practice is a well-described phenomenon in which patients with similar diagnoses, prognoses and demographic status receive different levels of care depending on when, where and by whom they are treated, despite agreed and documented evidence of best practice. The overutilization of health resources is also known to have a negative risk-benefit ratio. Unfortunately, both phenomena occur in several countries, especially in developed countries. In the light of this, the American Board of Internal Medicine launched the Choosing Wisely campaign, which has subsequently been implemented in several countries, including Portugal.

Atherosclerosis: The cost of illness in Portugal.

INTRODUCTION AND OBJECTIVES: Cardiovascular disease is the leading cause of death in Portugal and atherosclerosis is the most common underlying pathophysiological process. The aim of this study was to quantify the economic impact of atherosclerosis in Portugal by estimating disease-related costs. METHODS: Costs were estimated based on a prevalence approach and following a societal perspective. Three national epidemiological sources were used to estimate the prevalence of the main clinical manifestations of atherosclerosis. The annual costs of atherosclerosis included both direct costs (resource consumption) and indirect costs (impact on population productivity). These costs were estimated for 2016, based on data from the Hospital Morbidity Database, the health care database (SIARS) of the Regional Health Administration of Lisbon and Tagus Valley including real-world data from primary care, the 2014 National Health Interview Survey, and expert opinion. RESULTS: The total cost of atherosclerosis in 2016 reached 1.9 billion euros (58% and 42% of which was direct and indirect costs, respectively). Most of the direct costs were associated with primary care (55%), followed by hospital outpatient care (27%) and hospitalizations (18%). Indirect costs were mainly driven by early exit from the labor force (91%). CONCLUSIONS: Atherosclerosis has a major economic impact, being responsible for health expenditure equivalent to 1% of Portuguese gross domestic product and 11% of current health expenditure in 2016.

Functional Health Literacy: Psychometric Properties of the Newest Vital Sign for Portuguese Adolescents (NVS-PTeen).

Self-management of health requires skills to obtain, process, understand, and use health-related information. Assessment of adolescents' functional health literacy requires valid, reliable, and low-burden tools. The main objective of this study was to adapt and study the psychometric properties of the Newest Vital Sign for the Portuguese adolescents' population (NVS-PTeen). Classic psychometric indicators of reliability and validity were combined with item response theory (IRT) analyses in a cross-sectional survey, complemented with a 3-month test-retest assessment. The NVS-PTeen was self-administered to students enrolled in grades 8 to 12 (12 to 17 years old) in a school setting. Overall, 386 students (191 girls) from 16 classes of the same school participated in the study (mean age = 14.5; SD = 1.5). Internal reliability of the NVS-PTeen was α = 0.60. The NVS-PTeen total score was positively and significantly correlated with Portuguese (r = 0.28) and mathematics scores (r = 0.31), school years (r = 0.31), and age (r = 0.19). Similar to the original scale (for the U.S.), the NVS-PTeen is composed of two dimensions, reading-related literacy and numeracy. Temporal reliability is adequate, though with a learning effect. IRT analyses revealed differences in difficulty and discriminative capacity among items, all with adequate outfit and infit values. Results showed that the NVS-PTeen is valid and reliable, sensible to inter-individual educational differences, and adequate for regular screening of functional health literacy in adolescents.

[Analysis of the Cochrane Review: Antiplatelet Agents for Preventing Pre-Eclampsia and Its Complications. Cochrane Database Syst Rev. 2019;10:CD004659.] / Análise da Revisão Cochrane: O Papel dos Antiagregantes Plaquetários para Prevenir a Pré-Eclâmpsia e as Suas Complicações. Cochrane Database Syst Rev. 2019;10:CD004659.

Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia. This Cochrane review aimed to assess the effectiveness and safety of antiplatelet agents, such as aspirin and dipyridamole, when given to women at risk of developing preeclampsia. A systematic review of literature was carried out by searching the following databases up to September 2019: Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies. Seventy-seven trials were included, including 40 249 women at risk of developing pre-eclampsia. About 80% of these women were evaluated in nine of the 77 trials included, with eight of these nine trials providing individual data. Interventions were administration of an antiplatelet agent, and comparisons were either placebo or no antiplatelet. The present review provides high-quality evidence that administering low-dose aspirin (50 - 150 mg) to pregnant women led to small-to-moderate benefits, including reductions in the risk of pre-eclampsia, preterm birth, small-for-gestational age fetus, and fetal or neonatal death. Overall, administering antiplatelet agents to 1000 women led to 20 fewer pregnancies with serious adverse outcomes.

A pré-eclâmpsia está associada à produção intravascular deficiente de prostaciclina, um vasodilatador, e à produção excessiva de tromboxano, um vasoconstritor e estimulante da agregação plaquetária. Essas observações levaram à hipótese de os antiagregantes plaquetários, em particular o ácido acetilsalicílico, poderem, em dose reduzida, prevenir ou retardar o desenvolvimento da pré-eclâmpsia. Esta revisão da Cochrane teve como objetivo avaliar a eficácia e segurança de antiagregantes plaquetários comparativamente a placebo ou a ausência de tratamento, quando administrados a mulheres em risco de desenvolver pré-eclâmpsia. Foi realizada uma revisão sistemática da literatura até setembro de 2019, através de pesquisa nas seguintes bases de dados: Registo de Ensaios de Gravidez e Parto da Cochrane, ClinicalTrials.gov, Plataforma Internacional de Registo de Ensaios Clínicos da OMS (ICTRP) e listas de referência de estudos recuperados. Foram incluídos 77 ensaios clínicos aleatorizados, incluindo 40 249 mulheres grávidas em risco de desenvolver pré-eclâmpsia. Cerca de 80% destas mulheres foram avaliadas em nove dos 77 ensaios incluídos, sendo que oito destes nove ensaios disponibilizavam dados individuais. O ácido acetilsalicílico foi o antiagregante plaquetário avaliado na maioria dos ensaios, incluindo nos nove ensaios de maior dimensão. A presente revisão concluiu, com qualidade de evidência elevada, que a administração de ácido acetilsalicílico em dose reduzida (50 - 150 mg) a mulheres grávidas está associada a benefícios, considerados de magnitude pequena a moderada, na redução do risco de pré-eclâmpsia, parto prematuro, feto pequeno para a idade gestacional, e morte fetal ou neonatal. A administração de antiagregantes plaquetários a 1000 mulheres resultou em menos 20 gestações com desfechos adversos graves.

The burden of atherosclerosis in Portugal.

AIMS: This article sought to estimate the burden of disease attributable to atherosclerosis in mainland Portugal in 2016. METHODS AND RESULTS: The burden of atherosclerosis was measured in disability-adjusted life years following the latest 2010 Global Burden of Disease (GBD) methodology. Disability-adjusted life years were estimated as the sum of years of life lost (YLL) with years lived with disability (YLD). The following clinical manifestations of atherosclerosis were included: ischaemic heart disease (IHD) (including acute myocardial infarction, stable angina, and ischaemic heart failure), ischaemic cerebrovascular disease (ICVD), and peripheral arterial disease (PAD). Years of life lost were estimated based on all-cause mortality data for the Portuguese population and mortality due to IHD, ICVD, and PAD for the year 2016 sourced from national statistics. Standard life expectancy was sourced from the GBD study. Years lived with disability corresponded to the product of the number of prevalent cases by an average disability weight for all possible combinations of disease. Prevalence data for the different clinical manifestations of atherosclerosis were sourced from epidemiological studies. Disability weights were sourced from the published literature. In 2016, 15 123 deaths were attributable to atherosclerosis, which corresponded to 14.3% of overall mortality in mainland Portugal. Disability-adjusted life years totalled 260 943, 75% due to premature death (196 438 YLL) and 25% due to disability (64 505 YLD). CONCLUSION: Atherosclerosis entails a high disease burden to society. A large part of this burden would be avoidable if evidence-based effective and cost-effective interventions targeting known risk factors, from prevention to treatment, were implemented.

The Role of Health Preconditions on COVID-19 Deaths in Portugal: Evidence from Surveillance Data of the First 20293 Infection Cases.

BACKGROUND: It is essential to study the effect of potential co-factors on the risk of death in patients infected by COVID-19. The identification of risk factors is important to allow more efficient public health and health services strategic interventions with a significant impact on deaths by COVID-19. This study aimed to identify factors associated with COVID-19 deaths in Portugal. METHODS: A national dataset with the first 20,293 patients infected with COVID-19 between 1 January and 21 April 2020 was analyzed. The primary outcome measure was mortality by COVID-19, measured (registered and confirmed) by Medical Doctors serving as health delegates on the daily death registry. A logistic regression model using a generalized linear model was used for estimating Odds Ratio (OR) with 95% confidence intervals (95% CI) for each potential risk indicator. RESULTS: A total of 502 infected patients died of COVID-19. The risk factors for increased odds of death by COVID-19 were: sex (male: OR = 1.47, ref = female), age ((56-60) years, OR = 6.01; (61-65) years, OR = 10.5; (66-70) years, OR = 20.4; (71-75) years, OR = 34; (76-80) years, OR = 50.9; (81-85) years, OR = 70.7; (86-90) years, OR = 83.2; (91-95) years, OR = 91.8; (96-104) years, OR = 140.2, ref = (0-55)), Cardiac disease (OR = 2.86), Kidney disorder (OR = 2.95), and Neuromuscular disorder (OR = 1.58), while condition (None (absence of precondition); OR = 0.49) was associated with a reduced chance of dying after adjusting for other variables of interest. CONCLUSIONS: Besides age and sex, preconditions justify the risk difference in mortality by COVID-19.

The challenge of implementing Less is More medicine: A European perspective.

The concept of Less is More medicine emerged in North America in 2010. It aims to serve as an invitation to recognize the potential risks of overuse of medical care that may result in harm rather than in better health, tackling the erroneous assumption that more care is always better. In response, several medical societies across the world launched quality-driven campaigns ("Choosing Wisely") and published "top-five lists" of low-value medical interventions that should be used to help make wise decisions in each clinical domain, by engaging patients in conversations about unnecessary tests, treatments and procedures. However, barriers and challenges for the implementation of Less is More medicine have been identified in several European countries, where overuse is rooted in the culture and demanded by a society that requests certainty at almost any cost. Patients' high expectations, physician's behavior, lack of monitoring and pernicious financial incentives have all indirect negative consequences for medical overuse. Multiple interventions and quality-measurement efforts are necessary to widely implement Less is More recommendations. These also consist of a top-five list of actions: (1) a novel cultural approach starting from medical graduation courses, up to (2) patient and society education, (3) physician behavior change with data feedback, (4) communication training and (5) policy maker interventions. In contrast with the prevailing maximization of care, the optimization of care promoted by Less is More medicine can be an intellectual challenge but also a real opportunity to promote sustainable medicine. This project will constitute part of the future agenda of the European Federation of Internal Medicine.

Excess Mortality Estimation During the COVID-19 Pandemic: Preliminary Data from Portugal.

INTRODUCTION: Portugal is experiencing the effects of the COVID-19 pandemic since March 2020. All-causes mortality in Portugal increased during March and April 2020 compared to previous years, but this increase is not explained by COVID-19 reported deaths. The aim of this study was to analyze and consider other criteria for estimating excessive all-cause mortality during the early COVID-19 pandemic period. MATERIAL AND METHODS: Public data was used to estimate excess mortality by age and region between March 1 and April 22, proposing baselines adjusted for the lockdown period. RESULTS: An excess mortality of 2400 to 4000 deaths was observed. Excess mortality was associated with older age groups (over age 65) [corrected]. DISCUSSION: The data suggests a ternary explanation for early excess mortality: COVID-19, non-identified COVID-19 and decrease in access to healthcare. The estimates have implications in terms of communication of non-pharmaceutical actions, for research, and to healthcare professionals. CONCLUSION: Despite the inherent uncertainty, the excess mortality occurred between March 1 and April 22 could be 3.5- to 5-fold higher than what can be explained by the official COVID-19 deaths [corrected].

Introdução: Desde março 2020, Portugal tem sofrido os efeitos da pandemia COVID-19. A mortalidade por todas as causas aumentou em março e abril de 2020 comparativamente a anos anteriores, mas este aumento não é explicado pelas mortes reportadas de COVID-19. O objetivo deste estudo foi analisar e considerar outros critérios para estimar o excesso de mortalidade durante a pandemia COVID-19. Material e Métodos: Utilizaram-se bases de dados públicas para estimar o excesso de mortalidade por idade e região entre 1 de março e 22 de abril, propondo níveis basais ajustados ao período de estado de emergência em vigor. Resultados: Apesar da incerteza inerente, é seguro assumir um excesso de mortalidade observada de 2400 a 4000 mortes. O excesso de mortalidade encontra-se associado aos grupos etários mais idosos (idade superior a 65 anos). Discussão: Os dados sugerem uma explicação tripartida para o excesso de mortalidade: COVID-19, COVID-19 não identificado e diminuição do acesso a cuidados de saúde. As estimativas efetuadas possuem implicações ao nível da comunicação de acções não farmacológicas, da investigação científica e dos profissionais de saúde. Conclusão: Da análise dos resultados é possível concluir que o excesso de mortalidade ocorrido entre 1 de março e 22 de abril foi 3 a 5 vezes superior ao explicado pelas mortes por COVID-19 reportadas oficialmente.

Is olive oil good for you? A systematic review and meta-analysis on anti-inflammatory benefits from regular dietary intake.

The prevalence of non-communicable diseases is rapidly increasing, and evidence shows that diet and lifestyle are key areas of intervention to decrease their burden. Olive oil is considered one of the key nutritional components responsible for the benefits of the Mediterranean diet, which is characterized by the use of olive oil in meals as the main source of fat; a high consumption of water, fruits, nuts, vegetables, legumes, whole grains, spices, and herbs; a moderate consumption of dairy products (mainly cheese and yogurt), fish, poultry, and red wine; and a reduced consumption of red meat and processed foods. The aim of this review was to summarize evidence from randomized controlled trials on the effect of regular dietary intake of olive oil on three inflammatory markers: C-reactive protein, interleukin-6, and tumor necrosis factor-α. Reviewed RCTs reveal beneficial effects of olive oil by reducing levels of inflammation markers. Olive oil taken on a regular basis can be a good dietary fat alternative, especially to manage IL-6. However, further research is required to clarify the effects of olive oil consumption on inflammation, comparing to other fats. Moreover, olive oil daily dosage, different time-lenght intervention and follow-up periods should be taken into consideration.