Statins use for primary prevention of cardiovascular disease: A population-based digitally enabled real-world evidence cross-sectional study in primary care in Brazil.

BACKGROUND: Statins consist of the main strategy to reduce dyslipidemia-related cardiovascular risk. Nevertheless, there is scarce evidence on the real-world statins use in primary care settings in low-middle-income countries. OBJECTIVE: We conducted a cross-sectional retrospective study using anonymized data routinely collected by community health workers in Brazil aimed to evaluate statin use and associated factors in a primary prevention population with cardiovascular risk enhancers. METHODS: Study population consisted of adults with hypertension, diabetes and/or dyslipidemia. The primary and secondary outcomes were the proportion of individuals self-reporting statins use on any dose, and high-dose statins/high-intensity lipid lowering therapy (LLT) respectively. RESULTS: Of the 2,133,900 adult individuals on the database, 415,766 (19.5%) were included in the study cohort. From this cohort, 89.1% had hypertension, 28.9% diabetes and 5.5% dyslipidemia. The mean age was 61.5 (SD 14.5) years, 63.4% were female and 61.0% were of mixed-race. Only 2.6% and 0.1% of individuals self-reported the use of statins and high-dose statins/high-intensity LLT, respectively. Older age (OR 1.96; 95% CI 1.88,2.05;p < 0.001), living in the South region of Brazil (OR 4.39; 95%CI 3.97,4.85,p < 0.001), heart failure (OR 2.60; 95%CI 2.33,2.89,p < 0.001), chronic kidney disease (OR 1.49; 95%CI 1.35,1.64,p < 0.001) and anti-hypertensive medications use (OR 4.38; 95%CI 4.07,4.71,p < 0.001) were independently associated with statin use. CONCLUSION: In a real-world evidence study analyzing data routinely collected in a digitized primary care setting, we observed a very low use of statins in a primary prevention population with cardiovascular risk enhancers in Brazil. Socio-demographic factors and co-morbidities were associated to higher statins use rates.

Cardiovascular Statistics ­ Brazil 2023 / Estatística Cardiovascular ­ Brasil 2023

The publication Cardiovascular Statistics ­ Brazil aims to provide an annual compilation of data and research on the epidemiology of CVDs in Brazil.  The report integrates official statistics from the Brazilian Ministry of Health and other governmental entities alongside data from the GBD project, coordinated by the IHME at the University of Washington. Additionally, it incorporates data derived from various sources and scientific studies, including cohorts and registries, that relate to CVDs and their associated risk factors. This publication is intended for a wide range of individuals, including researchers, clinicians, patients, healthcare policymakers, media professionals, the general public, and other interested parties seeking extensive national data about heart disease and stroke.  Volunteer researchers from various Brazilian universities and research institutions carry out the project. The group is led by a five-member steering committee (ALPR, CAP, DCM, GMMO, and LCCB). The Brazilian Society of Cardiology fully supports this initiative, and the project receives collaborative support from the GBD Brazil Network and an International Committee (GAR, PP, and TAG) from both the IHME/University of Washington (GAR) and the World Heart Federation (PP and TAG). 

A publicação Estatística Cardiovascular ­ Brasil tem por objetivo fornecer uma compilação anual dos dados e das pesquisas sobre a epidemiologia das DCV no Brasil.  Este documento integra as estatísticas oficiais do Ministério da Saúde do Brasil e outras entidades governamentais ao lado de dados do projeto GBD, coordenado pelo IHME da Universidade de Washington. Além disso, incorpora dados derivados de várias fontes e estudos científicos, inclusive coortes e registros, relacionados às DCV e fatores de risco associados. Esta publicação destina-se a um público variado, incluindo pesquisadores, clínicos, pacientes, formuladores de políticas de saúde, profissionais da mídia, o público em geral e todos aqueles que buscam dados nacionais abrangentes sobre DCV e acidente vascular cerebral. Pesquisadores voluntários de várias universidades e instituições de pesquisa brasileiros realizaram este projeto. O grupo é liderado por um comitê diretivo com cinco membros (ALPR, CAP, DCM, GMMO e LCCB). A Sociedade Brasileira de Cardiologia apoia integralmente esta iniciativa e o projeto recebe colaboração da Rede GBD Brasil1 e do GBD International Committee (GAR, PP e TAG) do IHME/Universidade de Washington (GAR) e da World Heart Federation (PP e TAG). 

Economic valuation of the ecosystem of the high Andean hydrographic basin tributary of the Chumbao River, through multicriteria analysis.

Environmental wealth is the main basis of the social, cultural and economic development of a country, but if there is an absence of the valuation of these natural resources, it can lead to a disproportionate usufruct that causes the deterioration of the ecosystem and even collateral effects of human health. This research aimed to know the total economic value of the ecosystem of the high Andean water basin tributary of the Chumbao River, located between 2000 to 4800 meters above sea level belonging to the province of Andahuaylas, Apurimac region in Perú. The valuation procedure consisted of using the analytical method of multicriteria valuation applying the concept of Total Economic Value, which involved direct and indirect uses related to environmental assets, in which a collective panel of people from different training disciplines (experts) participated, which were made up of researchers, engineers, public officials, farmers and ecologists who had extensive knowledge about the environmental asset. of the geographical area in reference; and once the paired comparison survey was done, the total economic value was quantified up to three amounts, so the respondents were formed into three statistically significant segments (SIG<0.05). The cluster (1): assigned a weighting that quantifies to an economic value of USS 4,359,179,489.46; followed by cluster (2): an intermediate value of USS 4,029,902,444.41 and cluster (3): assigned a lower value to USS 774,163,167.16. Thus, it follows that, on average, 51.78% equals value in use and 48.21% equals value in non-use, respectively. This value expressed as an interval reflects the environmental ethical positions of the groups and makes available as an indicator to government authorities and society in order to exercise actions of environmental sustainability high andean.

Assessing statins use in a real-world primary care digital strategy: a cross-sectional analysis of a population-wide digital health approach.

Background: The digitization of the primary care system provides an opportunity to evaluate the current use of statins in secondary prevention populations (myocardial infarction or stroke). Methods: We conducted a cross-sectional study (ClinicalTrials.gov, NCT05285085), analysing anonymised data routinely collected by community health workers (CHW) in Brazil between May 2016 and September 2021 to assess the proportion of self-reported statins use and associated factors. Findings: From the 2,133,900 individuals on the database, 35,103 (1.6%), mean age 66.2 years (SD14.6), 49.5% (17,382/35,103) male sex, 50.5% (17,721/35,103) female sex, and 29.6% (10,381/34,975) Caucasians, had a previous myocardial infarction (MI) (n = 11,628; 33.1%) or stroke (n = 25,925; 73.9%). Approximately 50% (17,020/35,103) were from the Northeast region, 78.7% (27,605) from urban zones, and 39.4% (13,845) with social development index (SDI) >0.7. Overall, 6.7% (2346) and 0.6% (212) reported statins and high dose statins use, respectively. Age over 60 years old (OR 1.32 [95% CI 1.19-1.47), living in the Southern region (OR 4.53 [95% CI 3.66-5.60]), having a previous diagnosis of MI (OR 4.53 [95% CI 3.66-5.60]), heart failure (OR 2.29 [95% CI 1.13-1.47]), diabetes (OR 1.50 [95% CI 1.37-1.64]), dyslipidaemia (OR 2.90 [95% CI 2.55-3.29]), chronic kidney disease (OR 1.27 [95% CI 1.08-1.48]) and use of anti-hypertensives (OR 5.47 [95% CI 4.60-6.47]) were associated with statin use. Interpretation: The analysis of a real-world database from a digitized primary care system, allowed us to identify a very low use of statins in secondary prevention Brazilian patients, mostly influenced by socio-demographic factors and co-morbidities. Funding: Novartis Biociências, Brazil.

Microcapsules of Sacha Inchi seed oil (Plukenetia volubilis L.) obtained by spray drying as a potential ingredient to formulate functional foods.

Sacha Inchi seed oil (SIO) is rich in omega 3, 6, and 9 fatty acids with important health benefits, but is temperature sensitive. Spray drying is a technology that improves the long-term stability of bioactive compounds. This work aimed to study the effect of three different homogenization techniques on some physical properties and bioavailability of microcapsules of Sacha Inchi seed oil (SIO) emulsions obtained by spray drying. Emulsions were formulated with SIO (5%, w/w), maltodextrin:sodium caseinate as wall material (10%, w/w; 85:15), Tween 20 (1%, w/w) and Span 80 (0.5%, w/w) as surfactants and water up to 100% (w/w). Emulsions were prepared using high-speed (Dispermat D-51580, 18,000 rpm, 10 min), conventional (Mixer K-MLIM50N01, Turbo speed, 5 min), and ultrasound probe (Sonics Materials VCX 750, 35% amplitude, 750 W, 30 min) homogenization. SIO microcapsules were obtained in a Mini Spray B-290 (Büchi) using two inlet temperatures of the drying air (150 and 170 °C). Moisture, density, dissolution rate, hygroscopicity, drying efficiency (EY), encapsulation efficiency (EE), loading capacity, and oil release in digestive fluids in vitro were studied. Results showed that the microcapsules obtained by spray-drying had low moisture values and high encapsulation yield and efficiency values (greater than 50% and 70%, respectively). The thermogravimetric analysis indicates that heat protection was assured, enhancing the shelf life and the ability to withstand thermal food processing. Results suggest that spray-drying encapsulation could be a suitable technology to successfully microencapsulate SIO and enhance the absorption of bioactive compounds in the intestine. This work highlights the use of Latin American biodiversity and spray drying technology to ensure the encapsulation of bioactive compounds. This technology represents an opportunity for the development of new functional foods, improving the safety and quality of conventional foods.

New strategies to analyze argentatins A and B in guayule (Parthenium argentatum, A. Gray).

There is considerable interest in the exploitation of compounds belonging to the triterpenoid family from guayule (Parthenium argentatum, A. Gray), as they offer several beneficial effects to human health. The most abundant triterpenoids in guayule resin are the argentatins, which are currently analyzed by labor-intensive and time-consuming techniques. The purpose of the present study was to estimate argentatins and isoargentatins A and B in guayule using near-infrared spectroscopy (NIRS) and flow injection analysis (FIA). Results revealed that the best partial least squares regression model exhibited excellent correlation with the values estimated by NIRS calibration (r2c = 0.99-1.00) and cross-validation (r2cv = 0.94-0.99), and the residual predictive deviation was >3 in all cases. After optimization of the liquid chromatography-mass spectrometry and FIA parameters, the FIA mode could reliably collect data for argentatin A and B after applying a calculated coverage factor. In sum, NIRS and FIA appear to be a robust option for the estimation and routine analysis of argentatins in guayule stems and resin, respectively.

New amidine-benzenesulfonamides as iNOS inhibitors for the therapy of the triple negative breast cancer.

Triple negative breast cancer (TNBC) is a specific breast cancer subtype, and poor prognosis is associated to this tumour when it is in the metastatic form. The overexpression of the inducible Nitric Oxide Synthase (iNOS) is considered a predictor of poor outcome in TNBC patients, and this enzyme is reported as a valuable molecular target to compromise TNBC progression. In this work, new amidines containing a benzenesulfonamide group were designed and synthesized as selective iNOS inhibitors. An in vitro biological evaluation was performed to assess compounds activity against both the inducible and constitutive NOSs. The most interesting compounds 1b and 2b were evaluated on MDA-MB-231 cells as antiproliferative agents, and 1b capability to counteract cell migration was also studied. Finally, an in-depth docking study was performed to shed light on the observed potency and selectivity of action of the most promising compounds.

Digital Health-Enabled Clinical Trials in Stroke: Ready for Prime Time?

As stroke continues to represent a major global health care problem, advancing our knowledge of new effective and safe stroke interventions represents a public health priority. The identification of these therapies requires the conduct of high-quality and well-powered randomized clinical trials. Despite its potential to inform clinical practice, traditional randomized clinical trial models have their drawbacks, including elevated costs, long completion times, failure to recruit the target sample sizes, lack of diversity, and complex operational procedures. Therefore, improving the participants' experience and trials' overall efficiency constitutes an important unmet need. Innovative models such as virtual and decentralized patient-centric trials have been proposed as a valuable strategy in this pursuit. In this narrative review, we discuss the limitations of traditional randomized clinical trial models and present the concept, advantages, and challenges of decentralized digitally enabled approaches to the conduct of stroke clinical trials.

Bioactive imidamide-based compounds targeted against nitric oxide synthase.

The selective inhibition of inducible nitric oxide synthase (iNOS) has become an interesting goal for the treatment of diseases where the immune and inflammatory response of the organism is involved. Septic shock is one prominent example of this type of affections. In this paper, the design and synthesis of twelve substituted pyridinyl- imidamide derivatives is described, together with their biological evaluation as NOS inhibitors. The most potent and selective compound was N-(3-hydroxy-3-(pyridin-3-yl)propyl)acetimidamide 9a (IC50 = 4.6 µM, against iNOS). Pharmacological assays in aortic rat tissue, have confirmed its inhibitory activity on iNOS and the absence of undesired cardicovascular effects. In silico analysis of the most promising compounds (9a, 9b, 9e and 9g) have predicted good drug-likeness properties. Furthermore, they have shown an adequate cell viability. Docking studies carried out on 9a suggest a particular binding mode that involves the essential residue Glu377, and might explain its iNOS selectivity. From a chemical point of view, the article describes an unusual cyclization to obtain pyridinyl-pyrimidine derivatives with high yield.

Synthesis, bioevaluation and docking studies of new imidamide derivatives as nitric oxide synthase inhibitors.

In search of new Nitric Oxide Synthase (NOS) inhibitor agents, two isosteric series of derivatives with an imidamide scaffold (one of them with a hydroxyl group and the other with a carbonyl one) were synthesized and evaluated on inducible (iNOS) and neuronal (nNOS) isoforms. These compounds have been designed by combining a kynurenamine framework with an amidine moiety in order to improve selectivity for the inducible isoform. In general, the in vitro inhibitory assays exhibited better inhibition values on the iNOS isoform, being the N-(3-(2-amino-5-methoxyphenyl)-3-hydroxypropyl)-4-(trifluoromethyl)benzimidamide 4i the most active inhibitor with the highest iNOS selectivity, without inhibiting eNOS. Docking studies on the two most active compounds suggest a different binding mode on both isozymes, supporting the experimentally observed selectivity towards the inducible isoform. Physicochemical in silico studies suggest that these compounds possess good drug-likeness properties.

The effect of process variables on the physical properties and microstructure of HOPO nanoemulsion flakes obtained by refractance window.

Refractance window (RW) drying is considered an emerging technique in the food field due to its scalability, energy efficiency, cost and end-product quality. It can be used for obtaining flakes from high-oleic palm oil (HOPO) nanoemulsions containing a high concentration of temperature-sensitive active compounds. This work was thus aimed at studying the effect of temperature, thickness of the film drying, nanoemulsion process conditions, and emulsion formulation on the flakes' physical properties and microstructure. The results showed that HOPO flakes had good physical characteristics: 1.4% to 5.6% moisture content and 0.26 to 0.58 aw. Regarding microstructure, lower fractal dimension (FDt) was obtained when RW drying temperature increased, which is related to more regular surfaces. The results indicated that flakes with optimal physical properties can be obtained by RW drying of HOPO nanoemulsions.

Réplica de los autores a la carta: Acerca del conocimiento sobre dolor en enfermeras de cuidados intensivos / About knowledge about pain in intensive care nurses

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Effect of the aniline fragment in Pt(II) and Pt(IV) complexes as anti-proliferative agents. Standard reduction potential as a more reliable parameter for Pt(IV) compounds than peak reduction potential.

The problems of resistance and side effects associated with cisplatin and other chemotherapeutic drugs have boosted research aimed at finding new compounds with improved properties. The use of platinum(IV) prodrugs is one alternative, although there is some controversy regarding the predictive ability of the peak reduction potentials. In the work described here a series of fourteen chloride Pt(II) and Pt(IV) compounds was synthesised and fully characterised. The compounds contain different bidentate arylazole heterocyclic ligands. Their cytotoxic properties against human lung carcinoma (A549), human breast carcinoma (MCF7) and human colon carcinoma (HCT116 and HT29) cell lines were studied. A clear relationship between the type of ligand and the anti-proliferative properties was found, with the best results obtained for the Pt(II) compound that contains an aniline fragment, (13), thus evidencing a positive effect of the NH2 group. Stability and aquation studies in DMSO, DMF and DMSO/water mixtures were carried out on the active complexes and an in-depth analysis of the two aquation processes, including DFT analysis, of 13 was undertaken. It was verified that DNA was the target and that cell death occurred by apoptosis in the case of 13. Furthermore, the cytotoxic derivatives did not exhibit haemolytic activity. The reduction of the Pt(IV) compounds whose Pt(II) congeners were active was studied by several techniques. It was concluded that the peak reduction potential was not useful to predict the ability for reduction. However, a correlation between the cytotoxic activity and the standard reduction potential was found.