Cost-effectiveness of semaglutide 2.4 mg in chronic weight management in Portugal.

BACKGROUND: Obesity and overweight are a significant public health concern. Subcutaneous semaglutide 2.4 mg injection is a glucagon-like peptide-1 (GLP-1) analogue approved by the European Medicines Agency as an adjunct to a reduced calorie diet and increased physical activity (diet and exercise, D&E) for the treatment obesity and overweight in the presence of at least one weight related comorbidity. This study aimed to assess the cost-effectiveness of semaglutide 2.4 mg in combination with D&E compared to D&E alone for the Portuguese setting. METHODS: Analysis were conducted using the Core Obesity Model (COM) version 18, a Markov state transition cohort model, to predict the health outcomes and costs of weight related complications based on changes in surrogate endpoints. Efficacy and safety data were sourced from the STEP trials (Body Mass Index, systolic blood pressure and glycemic status) from a cohort of adults aged on average 48 years with obesity (BMI ≥ 30 kg/m2) and ≥ 1 obesity-related comorbidities, over a time horizon of 40 years. Costs were estimated from the perspective of the Portuguese National Health Service. Sensitivity analyses were conducted to test the robustness of results across a range of assumptions. RESULTS: On a patient level, Semaglutide 2.4 mg in addition to D&E compared to D&E alone, improved QALYs by 0.098 and yielded higher costs by 1,325 EUR over a 40-year time horizon, with an ICER of 13,459 EUR per QALY gained and 100% probability of cost-effectiveness at the given WTP. Semaglutide 2.4 mg remained cost-effective across all different scenarios and sensitivity analysis at a WTP of 20,000 EUR per QALY. Among the subpopulations examined, Semaglutide 2.4 mg yielded ICERs of 18,459 EUR for patients with BMI ≥ 30 kg/m2 and of 22,657 EUR for patients with BMI ≥ 35 kg/m2. CONCLUSIONS: Semaglutide 2.4 mg was cost-effective compared to D&E alone for patients with obesity (BMI ≥ 30 kg/m2) and weight related comorbidities in Portugal, over a 40-year time horizon.

Stone Pine (Pinus pinea L.) High-Added-Value Genetics: An Overview.

Stone pine (Pinus pinea L.) has received limited attention in terms of genetic research. However, genomic techniques hold promise for decoding the stone pine genome and contributing to developing a more resilient bioeconomy. Retrotransposon and specific genetic markers are effective tools for determining population-specific genomic diversity. Studies on the transcriptome and proteome have identified differentially expressed genes PAS1, CLV1, ATAF1, and ACBF involved in shoot bud formation. The stone pine proteome shows variation among populations and shows the industrial potential of the enzyme pinosylvin. Microsatellite studies have revealed low levels of polymorphism and a unique genetic diversity in stone pine, which may contribute to its environmental adaptation. Transcriptomic and proteomic analyses uncover the genetic and molecular responses of stone pine to fungal infections and nematode infestations, elucidating the defense activation, gene regulation, and the potential role of terpenes in pathogen resistance. Transcriptomics associated with carbohydrate metabolism, dehydrins, and transcription factors show promise as targets for improving stone pine's drought stress response and water retention capabilities. Stone pine presents itself as an important model tree for studying climate change adaptation due to its characteristics. While knowledge gaps exist, stone pine's genetic resources hold significant potential, and ongoing advancements in techniques offer prospects for future exploration.

Measuring the value of solidarity: The abem financial assistance program for out-of-pocket payments on pharmacy medicines in Portugal.

OBJECTIVE: Out-of-pocket payments for prescribed medicines are still comparatively high in Portugal. The abem program was launched in Portugal in May 2016 to aid vulnerable groups by completely covering out-of-pocket costs of prescribed medicines in community pharmacies. This study assesses the impact of the program on poverty and catastrophic health expenditures. METHODS: A longitudinal study was carried out with the analysis of several program databases (from the beginning of the program in May 2016 to September 2018) covering the cohorts of beneficiaries, daily data on medicines dispensed, social referencing entities, and solidarity pharmacies. The study provides estimates of standard poverty measures (intensity and severity) as well as the incidence of catastrophic health expenditures. RESULTS: More than 6000 beneficiaries were supported (56.8% female, 34.7% aged 65 or over), encompassing 127,510 medicines (mainly nervous system and cardiovascular system) with an average 26.9% co-payment (payments totalling €1.5 million). The program achieved substantial reductions in poverty (3.4% in intensity, 5.6% in severity), and eliminated cases with catastrophic health expenditures in medicines that would have affected 7.5% of the beneficiaries. CONCLUSIONS: Findings confirm a continuous increase in the number of beneficiaries, enabling access to medicines especially for the vulnerable elderly, and a sizable impact on eliminating out-of-pocket payments for medicines in the target population.

Itchy Skin: A Challenging Differential Diagnosis Between Mycosis Fungoides and Sézary Syndrome.

Primary cutaneous lymphomas represent a diverse spectrum of T-cell and B-cell lymphomas with their primary skin manifestation. Among these, mycosis fungoides (MF) and Sézary syndrome (SS) represent classic forms of cutaneous T-cell lymphomas (CTCLs). This report details the case of a 67-year-old female who presented with longstanding pruritic skin lesions, initially misdiagnosed and managed as eczema. The diagnostic process ultimately revealed the presence of Sézary cells in the peripheral blood smear (PBS). The SS diagnosis was confirmed based on CD4 positivity and CD7 negativity as determined by flow cytometry. The disease was staged as IVA1 (T2N0M1B2). The patient exhibited partial improvement with oral corticosteroid therapy. This report underscores the critical importance of integrating clinical evaluation and blood findings to distinguish between MF and SS. The progression of a circulating clone signals a poor prognosis, requiring surveillance and consideration of targeted therapies to enhance patient outcomes and improve their quality of life. Early detection remains paramount in the management of these rare cutaneous lymphomas, which are associated with unique therapeutic challenges.

Microbiological Assessment of White Button Mushrooms with an Edible Film Coating.

The development of edible coatings incorporating bioextracts from mushrooms native to Portuguese forests aims to enhance the value of the endogenous forest and mycological resources by harnessing their potential as a source of antimicrobial and antioxidant compounds. Edible coatings represent an important pathway to decreasing food waste and contributing to implementing a circular bioeconomy. The coating should result in product valorization through improved preservation/conservation, increased shelf life, as well as enhancement of its antioxidant and enzymatic properties. To evaluate the effectiveness of an edible coating on fungal food matrices, a 14-day shelf-life study was conducted, wherein both coated and untreated mushrooms were examined under controlled storage temperatures of 4 °C and 9.3 °C. Agaricus bisporus was chosen as the food matrix for its bioeconomy significance, and Pleurotus eryngii was selected for the preparation of the food-based coating due to its profile of bioactive compounds. Microbiological analysis and physicochemical monitoring were conducted on the food matrices and the coating. Coated mushrooms had less mass loss and color change, and had better texture after 14 days. Microbiological analysis revealed that the coating had no antimicrobial activity. Overall, the coating improved the shelf life of the coated mushrooms but had less effect on the microbial community.

[Oral Anticoagulation and the Incidence of Stroke Associated with Atrial Fibrillation in Mainland Portugal: A Modelling Study]. / Anticoagulação Oral e Incidência de Acidente Vascular Cerebral Associado a Fibrilhação Auricular em Portugal Continental: Um Estudo de Modelação.

INTRODUCTION: Atrial fibrillation is the most prevalent persistent dysrhythmia, contributing to a significant social and economic burden. The main objective of this study was to evaluate the association between oral anticoagulant use and the incidence of stroke associated with atrial fibrillation, in mainland Portugal. METHODS: The number of episodes of inpatient care with a main diagnosis of stroke and an additional diagnosis of atrial fibrillation, occurring monthly between January 2012 and December 2018, in individuals aged 18 years or over, was extracted from the hospital morbidity database. The number of patients with an atrial fibrillation code documented in this database was used as a proxy for the prevalence of known atrial fibrillation. The number of anticoagulated patients was estimated from total medicine sales of vitamin K antagonists and novel oral anticoagulants (apixaban, dabigatran, edoxaban and rivaroxaban) in mainland Portugal. Descriptive analyses were performed, and seasonal autoregressive integrated moving average (SARIMA) models were built using the R software. RESULTS: The mean number of episodes of stroke per month was 522 (± 57). The number of anticoagulated patients increased gradually from 68 943 to 180 389 per month. The decreasing trend in the number of episodes has been observed since 2016, along with the increased use of new oral anticoagulants compared to vitamin K antagonists. The final model indicated that the increase in oral anticoagulation use between 2012 and 2018, in mainland Portugal, was associated with a decrease in the number of episodes of stroke associated with atrial fibrillation. It was estimated that the shift in the type of anticoagulation used, between 2016 and 2018, was associated with a reduction of 833 episodes of stroke in patients with atrial fibrillation (4.2%). CONCLUSION: The use of oral anticoagulation was associated with a reduced incidence of stroke in patients with atrial fibrillation in mainland Portugal. This reduction was more relevant in the period between 2016 and 2018, and is probably related with the introduction of the novel oral anticoagulants.

Introdução: A fibrilhação auricular é a disritmia persistente mais prevalente, tendo um importante impacto social e económico. O objetivo principal deste estudo foi avaliar a associação entre a utilização de anticoagulantes orais e a incidência de acidente vascular cerebral associado a fibrilhação auricular, em Portugal continental. Métodos: A base de dados de morbilidade hospitalar foi utilizada para a contabilização dos episódios de internamento com um diagnóstico principal de acidente vascular cerebral e um diagnóstico adicional de fibrilhação auricular, ocorridos durante cada mês do período em análise (janeiro de 2012 a dezembro de 2018), em indivíduos com idade igual ou superior a 18 anos. O número de doentes com registo de fibrilhação auricular presentes nesta base de dados foi utilizado como um proxy da prevalência de fibrilhação auricular conhecida. O número de doentes anticoagulados foi estimado a partir das estatísticas das vendas de antagonistas da vitamina K e novos anticoagulantes orais (apixabano, dabigatrano, edoxabano e rivaroxabano) em Portugal continental. Foi realizada uma análise descritiva das variáveis, construindo-se depois modelos auto-regressivos integrados de médias móveis sazonais (seasonal autoregressive integrated moving average, SARIMA), com recurso ao software R. Resultados: Ocorreram, em média, 522 (± 57) episódios de acidente vascular cerebral por mês. Verificou-se um aumento gradual do número de doentes anticoagulados, passando de 68 943 para 180 389, por mês. A tendência decrescente no número de episódios verificou-se a partir de 2016, a par da maior utilização dos novos anticoagulantes orais, comparativamente aos antagonistas da vitamina K. O modelo final estimado indicou que o aumento do consumo de anticoagulação oral entre 2012 e 2018 em Portugal continental foi associado a um decréscimo do número de acidentes vasculares cerebrais associados a fibrilhação auricular. Estimou-se que, entre 2016 e 2018, a mudança no tipo de anticoagulação se associou a uma redução de 833 episódios de acidentes vascular cerebrais em doentes com fibrilhação auricular (4,2%). Conclusão: A anticoagulação oral associou-se à redução da incidência de acidente vascular cerebral em doentes com fibrilhação auricular, em Portugal continental. Esta redução foi mais relevante no período 2016 a 2018, em provável relação com a introdução dos novos anticoagulantes orais.

Nanoparticles as a Delivery System of Antigens for the Development of an Effective Vaccine against Toxoplasma gondii.

Nanoparticles include particles ranging in size from nanometers to micrometers, whose physicochemical characteristics are optimized to make them appropriate delivery vehicles for drugs or immunogens important in the fight and/or prevention of infectious diseases. There has been a rise in the use of nanoparticles in preventive vaccine formulations as immunostimulatory adjuvants, and as vehicles for immunogen delivery to target immune cells. Toxoplasma is important worldwide, and may cause human toxoplasmosis. In immunocompetent hosts, infection is usually asymptomatic, but in immunocompromised patients it can cause serious neurological and ocular consequences, such as encephalitis and retinochoroiditis. Primary infection during pregnancy may cause abortion or congenital toxoplasmosis. Currently, there is no effective human vaccine against this disease. Evidence has emerged from several experimental studies testing nanovaccines showing them to be promising tools in the prevention of experimental toxoplasmosis. For the present study, a literature review was carried out on articles published over the last 10 years through the PubMed database, pertaining to in vivo experimental models of T. gondii infection where nanovaccines were tested and protection and immune responses evaluated. This review aims to highlight the way forward in the search for an effective vaccine for toxoplasmosis.

A cross-sectional assessment of frailty, falls and perceptions of ageing in people living with HIV using an mHealth platform.

OBJECTIVE: To evaluate frailty, falls and perceptions of ageing among clinically stable individuals with HIV, engaged with remote healthcare delivered via a novel smartphone application. METHODS: This was a multi-centre European cross-sectional, questionnaire-based sub-study of EmERGE participants. Frailty was assessed using the five-item FRAIL scale. Present criteria were summed and categorized as follows: 0, robust; 1-2, pre-frail; 3-5, frail. Falls history and EQ-5D-5L quality of life measure were completed. Participants were asked their felt age and personal satisfaction with ageing. RESULTS: A total of 1373 participated, with a mean age of 45 (± 9.8) years. Frailty was uncommon at 2%; 12.4% fell in the previous year, 58.8% of these recurrently. Mood symptoms and pain were prevalent, at 43.3% and 31.8%, respectively. Ageing satisfaction was high at 76.4%, with 74.6% feeling younger than their chronological age; the mean felt age was 39.3 years. In multivariable analysis, mood symptoms and pain were positively associated with frailty, falls and ageing dissatisfaction. An increase in pain severity and mood symptoms were respectively associated with 34% and 63% increased odds of pre-frailty/frailty. An increment in pain symptoms was associated with a 71% increase in odds of falling. Pain was associated with ageing poorly, as were mood symptoms, with odds of dissatisfaction increasing by 34% per increment in severity. CONCLUSIONS: Although uncommon, frailty, falls and ageing dissatisfaction were seen in a younger cohort with medically stable HIV infection using a remote care model, promoting screening as advocated by European guidelines. These were more common in those with pain or mood symptoms, which should be proactively managed in clinical care and explored further in future research.

Efficiency of the EmERGE Pathway of Care in Five European HIV Centres.

OBJECTIVE: We aimed to calculate the efficiency of the EmERGE Pathway of Care in five European HIV clinics, developed and implemented for medically stable people living with HIV. METHODS: Participants were followed up for 1 year before and after implementation of EmERGE, between April 2016 and October 2019. Micro-costing studies were performed in the outpatient services of the clinics. Unit costs for outpatient services were calculated in national currencies and converted to US$ 2018 OECD purchasing parity prices to enable between clinic comparisons in terms of outcomes and costs. Unit costs were linked to the mean use of services for medically stable people living with HIV,  before and after implementation of EmERGE. Primary outcome measures were CD4 count and viral load; secondary outcomes were patient activation (PAM13) and quality of life (PROQOL-HIV). Out-of-pocket expenditure data were collected. RESULTS: There were 2251 participants: 87-93% were male, mean age at entry was 41-47 years. Medically stable people living with HIV had outpatient visits in four sites which decreased by 9-31% and costs by 5-33%; visits and costs increased by 8% in one site, which had to revert back to face-to-face visits. Antiretroviral drugs comprised 83-91% of annual costs: the Portuguese site had the highest antiretroviral drug costs in US$ purchasing parity prices. Primary and secondary outcome measures of participants did not change during the study. CONCLUSIONS: EmERGE is acceptable and provided cost savings in different socio-economic settings. Antiretroviral drug costs remain the main cost drivers in medically stable people living with HIV. While antiretroviral drug prices in local currencies did not differ that much between countries, conversion to US$ purchasing parity prices revealed antiretroviral drugs were more expensive in the least wealthy countries. This needs to be taken into consideration when countries negotiate drug prices with pharmaceutical vendors. Greater efficiencies can be anticipated by extending the use of the EmERGE Pathway to people with complex HIV infection or other chronic diseases. Extending such use should be systematically monitored, implementation should be evaluated and funding should be provided to monitor and evaluate future changes in service provision.

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.

Bisphenols A, F, S and AF trigger apoptosis and/or endoplasmic reticulum stress in human endometrial stromal cells.

Disruption of non-differentiated endometrial stromal cells could have noxious consequences in female reproduction, impairing endometrial remodelling and implantation. Following the classification of bisphenol A (BPA) as an endocrine disrupting chemical, it started to be gradually withdrawn from the market, being substituted by structural analogues, whose effects in human health are not fully understood. This work used a telomerase-immortalized human endometrial stromal cell line (St-T1b) to study the effects of BPA and its three most commercialized structural analogues (ranked: bisphenols S, F and AF) on endometrial stromal cells to understand their effects on female reproductive function. Bisphenols showed dissimilar effects. All four compounds generated endoplasmic reticulum (ER) stress. In addition, bisphenols A, F and AF induced apoptosis through different mechanisms, with bisphenol AF causing cell cycle arrest at G2/M phase. Bisphenol AF decreased mitochondrial transmembrane potential and bisphenols A, F and AF produced oxidative stress.

A biomechanical study of the birth position: a natural struggle between mother and fetus.

Birth trauma affects millions of women and infants worldwide. Levator ani muscle avulsions can be responsible for long-term morbidity, associated with 13-36% of women who deliver vaginally. Pelvic floor injuries are enhanced by fetal malposition, namely persistent occipito-posterior (OP) position, estimated to affect 1.8-12.9% of pregnancies. Neonates delivered in persistent OP position are associated with an increased risk for adverse outcomes. The main goal of this work was to evaluate the impact of distinct fetal positions on both mother and fetus. Therefore, a finite element model of the fetal head and maternal structures was used to perform childbirth simulations with the fetus in the occipito-anterior (OA) and OP position of the vertex presentation, considering a flexible-sacrum maternal position. Results demonstrated that the pelvic floor muscles' stretch was similar in both cases. The maximum principal stresses were higher for the OP position, and the coccyx rotation reached maximums of 2.17[Formula: see text] and 0.98[Formula: see text] for the OP and OA positions, respectively. Concerning the fetal head, results showed noteworthy differences in the variation of diameters between the two positions. The molding index is higher for the OA position, with a maximum of 1.87. The main conclusions indicate that an OP position can be more harmful to the pelvic floor and pelvic bones from a biomechanical point of view. On the other side, an OP position can be favorable to the fetus since fewer deformations were verified. This study demonstrates the importance of biomechanical analyses to further understand the mechanics of labor.

Anticoagulation therapy in patients with post-operative atrial fibrillation: Systematic review with meta-analysis.

BACKGROUND: Post-operative atrial fibrillation (POAF) is a relevant complication after surgery. Several studies have shown that POAF has important consequences for long-term morbidity and mortality, by increasing the risk of thromboembolic events. However, the use of oral anticoagulation (OAC) is not well established in this context. METHODS: We searched MEDLINE, CENTRAL, PsycInfo and Web of Science for clinical trials and observational studies evaluating anticoagulation vs. no anticoagulation in patients with POAF (after cardiac or non-cardiac surgery). Data were screened and extracted by two independent reviewers. We performed a random- effects model to estimate the pooled odds ratio (OR) with 95% Confidence Intervals (CI), and heterogeneity was evaluated by I2 statistics. The outcomes of interest were all-cause mortality, thromboembolic events, and bleeding events. RESULTS: Overall, 10 observational retrospective studies were included: 5 studies with 203,946 cardiac surgery POAF patients, and 5 studies with 29,566 patients with POAF after non-cardiac surgery. In cardiac surgery POAF, the OAC use was associated with lower risk of thromboembolic events (OR 0.68; 95%CI 0.47-0.96, I2 = 31%; 4 studies) and the bleeding risk was significantly increased (OR 4.30; 95%CI 3.69 to 5.02, 1 study). In non-cardiac surgery POAF, OAC did not significantly reduce the risk of thromboembolic events (OR 0.71, 95%CI 0.33-1.15; I2 = 79%; 5 studies) but was associated with increased risk of bleeding (OR 1.20, 95%CI 1.10-1.32, I2 = 0%; 3 studies). Mortality was not significantly reduced in both cardiac and non-cardiac surgery POAF. CONCLUSION: Oral anticoagulation was associated with a lower risk of thromboembolic events in patients with POAF following cardiac surgery but not in non-cardiac surgery. Bleeding risk was increased in both settings. The confidence on pooled results is at most low, and further data, namely randomized controlled trials are necessary to derive robust conclusions.

The efficiency of the EmERGE platform for medically stable people living with HIV in Portugal.

Background: The aim of this study was to calculate the cost-effectiveness of the EmERGE Pathway of Care for medically stable people living with HIV in the Hospital Capuchos, Centro Hospitalar Universitário de Lisboa Central (HC-CHLC). The app enables individuals to receive HIV treatment information and communicate with caregivers. Methods: This before-and-after study collected the use of services data 1 year before implementation and after implementation of EmERGE from November 1, 2016, to October 30, 2019. Departmental unit costs were calculated and linked to mean use of outpatient services per patient-year (MPPY). Annual costs per patient-year were combined with primary (CD4 count; viral load) and secondary outcomes (PAM-13; PROQOL-HIV). Results: Five hundred eighty-six EmERGE participants used HIV outpatient services. Annual outpatient visits decreased by 35% from 3.1 MPPY (95% confidence interval [CI]: 3.0-3.3) to 2.0 (95% CI: 1.9-2.1) as did annual costs per patient-year from €301 (95% CI: €288-€316) to €193 (95% CI: €182-€204). Laboratory tests and costs increased by 2%, and radiology investigations decreased by 40% as did costs. Overall annual cost for HIV outpatient services decreased by 5% from €2093 (95% CI: €2071-€2112) to €1984 (95% CI: €1968-€2001); annual outpatient costs decreased from €12,069 (95% CI: €12,047-€12,088) to €11,960 (95% CI: €11,944-€11,977), with 83% of annual cost because of antiretroviral therapy (ART). Primary and secondary outcome measures did not differ substantially between periods. Conclusions: The EmERGE Pathway produced cost savings after implementation-extended to all people living with HIV additional savings are likely to be produced, which can be used to address other needs. Antiretroviral drugs (ARVs) were the main cost drivers and more expensive in Portugal compared with ARV costs in the other EmERGE sites.

Promising Drug Targets and Compounds with Anti-Toxoplasma gondii Activity.

Toxoplasmosis is a parasitic disease caused by the globally distributed protozoan parasite Toxoplasma gondii, which infects around one-third of the world population. This disease may result in serious complications for fetuses, newborns, and immunocompromised individuals. Current treatment options are old, limited, and possess toxic side effects. Long treatment durations are required since the current therapeutic system lacks efficiency against T. gondii tissue cysts, promoting the establishment of latent infection. This review highlights the most promising drug targets involved in anti-T. gondii drug discovery, including the mitochondrial electron transport chain, microneme secretion pathway, type II fatty acid synthesis, DNA synthesis and replication and, DNA expression as well as others. A description of some of the most promising compounds demonstrating antiparasitic activity, developed over the last decade through drug discovery and drug repurposing, is provided as a means of giving new perspectives for future research in this field.

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.

Effect of the birthing position on its evolution from a biomechanical point of view.

BACKGROUND AND OBJECTIVE: During vaginal delivery, several positions can be adopted by the mother to be more comfortable and to help the labor process. The positions chosen are very influenced by factors such as monitoring and intervention during the second stage of labor. However, there is limited evidence to support the most ideal birthing position. This work aims at contributing to a better knowledge associated with the widening of the pubic symphysis and the biomechanics of flexible and non-flexible sacrum positions that can be adopted during the second stage of labor, as well as their resulting pathophysiological consequences. METHODS: A validated computational model composed by the pelvic floor muscles attached to the bones, and a fetus head was used to simulate vaginal deliveries. This model was modified to mimic two birthing positions: one that allows the free movement of the coccyx as in flexible sacrum positions and other in which this movement is more restricted as in non-flexible sacrum positions. The widening of the pubic symphysis was also considered to facilitate the passage of the fetus head. RESULTS: The results obtained showed that, in non-flexible sacrum positions, where the coccyx movement is restricted, occur a rotation of 3.6° of the coccyx and a widening of 6 mm of the pubic symphysis. In contrast, in flexible sacrum positions, where the coccyx is free to move, occur a rotation of 15.7° of the coccyx and a widening of the pubic symphysis of 3 mm, appearing to be more beneficial for the mother's pelvis, but slightly higher stresses were detected in the pelvic floor muscles. CONCLUSIONS: Globally, the results obtained allow to conclude that different birthing positions lead to changes in the female pelvic space, so certain positions can be adopted by the mother during the second stage of labor to reduce the risk of obstructed labor and the development of several dysfunctions. More specifically, flexible sacrum positions, such as kneeling, standing, squatting and sitting positions, are more beneficial for the bone structure of her pelvis as they allow a higher coccyx movement and lower widening of the pubic symphysis.

IFNγ and iNOS-Mediated Alterations in the Bone Marrow and Thymus and Its Impact on Mycobacterium avium-Induced Thymic Atrophy.

Disseminated infection with the high virulence strain of Mycobacterium avium 25291 leads to progressive thymic atrophy. We previously showed that M. avium-induced thymic atrophy results from increased glucocorticoid levels that synergize with nitric oxide (NO) produced by interferon gamma (IFNγ) activated macrophages. Where and how these mediators act is not understood. We hypothesized that IFNγ and NO promote thymic atrophy through their effects on bone marrow (BM) T cell precursors and T cell differentiation in the thymus. We show that M. avium infection cause a reduction in the percentage and number of common lymphoid progenitors (CLP). Additionally, BM precursors from infected mice show an overall impaired ability to reconstitute thymi of RAGKO mice, in part due to IFNγ. Thymi from infected mice present an IFNγ and NO-driven inflammation. When transplanted under the kidney capsule of uninfected mice, thymi from infected mice are unable to sustain T cell differentiation. Finally, we observed increased thymocyte death via apoptosis after infection, independent of both IFNγ and iNOS; and a decrease on active caspase-3 positive thymocytes, which is not observed in the absence of iNOS expression. Together our data suggests that M. avium-induced thymic atrophy results from a combination of defects mediated by IFNγ and NO, including alterations in the BM T cell precursors, the thymic structure and the thymocyte differentiation.

Pneumococcal vaccination in adults at very high risk or with established cardiovascular disease: systematic review and meta-analysis.

AIMS: There are several guidelines that recommend pneumococcal vaccination (PPSV23 and/or PCV13) in adults with a history of cardiovascular disease (established heart failure, coronary disease, and cerebrovascular disease) or at a very high risk of cardiovascular disease. However, there is no randomized controlled trial (RCT) systematic review that evaluates the impact of vaccination on all-cause mortality compared to no vaccination in this particular population. Our objective is to conduct a systematic review and meta-analysis of the impact of pneumococcal vaccination in the referred population. METHODS AND RESULTS: We searched CENTRAL and MEDLINE for relevant RCTs and observational studies. Data were screened, extracted, and appraised by two independent reviewers. We pooled results using a random effects model, and used hazard ratios (HRs) with 95% confidence intervals (CIs) to assess measure of effect. The primary outcome was all-cause mortality and we assessed the confidence in the evidence using the GRADE framework. No RCTs were found. Seven observational studies were included for analyses. Pooled results from five studies enrolling a total of 163 756 participants showed a significant decrease in all-cause mortality (HR 0.78, 95% CI 0.73-0.83, very low confidence), without statistically significant heterogeneity (χ2 test P = 0.21; I2 = 32%). CONCLUSIONS: Pneumococcal vaccination was associated with a 22% decrease of all-cause mortality in patients with cardiovascular disease or at a very high cardiovascular risk. However, limitations due to study design and the serious risk of bias in three of the included studies leads to a decreased level of result confidence.

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.