Methodological quality and clinical recommendations of guidelines on the management of dyslipidaemias for cardiovascular disease risk reduction: a systematic review and an appraisal through AGREE II and AGREE REX tools.

BACKGROUND: Clinical practice guidelines (CPGs) are statements to assist practitioners and stakeholders in decisions about healthcare. Low methodological quality guidelines may prejudice decision-making and negatively affect clinical outcomes in non-communicable diseases, such as cardiovascular diseases worsted by poor lipid management. We appraised the quality of CPGs on dyslipidemia management and synthesized the most updated pharmacological recommendations. METHODS: A systematic review following international recommendations was performed. Searches to retrieve CPG on pharmacological treatments in adults with dyslipidaemia were conducted in PubMed, Scopus, and Trip databases. Eligible articles were assessed using AGREE II (methodological quality) and AGREE-REX (recommendation excellence) tools. Descriptive statistics were used to summarize data. The most updated guidelines (published after 2019) had their recommendations qualitatively synthesized in an exploratory analysis. RESULTS: Overall, 66 guidelines authored by professional societies (75%) and targeting clinicians as primary users were selected. The AGREE II domains Scope and Purpose (89%) and Clarity of Presentation (97%), and the AGREE-REX item Clinical Applicability (77.0%) obtained the highest values. Conversely, guidelines were methodologically poorly performed/documented (46%) and scarcely provided data on the implementability of practical recommendations (38%). Recommendations on pharmacological treatments are overall similar, with slight differences concerning the use of supplements and the availability of drugs. CONCLUSION: High-quality dyslipidaemia CPG, especially outside North America and Europe, and strictly addressing evidence synthesis, appraisal, and recommendations are needed, especially to guide primary care decisions. CPG developers should consider stakeholders' values and preferences and adapt existing statements to individual populations and healthcare systems to ensure successful implementation interventions.

Naringenin-4'-glucuronide as a new drug candidate against the COVID-19 Omicron variant: a study based on molecular docking, molecular dynamics, MM/PBSA and MM/GBSA.

This study aimed to identify natural bioactive compounds (NBCs) as potential inhibitors of the spike (S1) receptor binding domain (RBD) of the COVID-19 Omicron variant using computer simulations (in silico). NBCs with previously proven biological in vitro activity were obtained from the ZINC database and analyzed through virtual screening, molecular docking, molecular dynamics (MD), molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA), and molecular mechanics/generalized Born surface area (MM/GBSA). Remdesivir was used as a reference drug in docking and MD calculations. A total of 170,906 compounds were analyzed. Molecular docking screening revealed the top four NBCs with a high affinity with the spike (affinity energy <-7 kcal/mol) to be ZINC000045789238, ZINC000004098448, ZINC000008662732, and ZINC000003995616. In the MD analysis, the four ligands formed a complex with the highest dynamic equilibrium S1 (mean RMSD <0.3 nm), lowest fluctuation of the complex amino acid residues (RMSF <1.3), and solvent accessibility stability. However, the ZINC000045789238-spike complex (naringenin-4'-O glucuronide) was the only one that simultaneously had minus signal (-) MM/PBSA and MM/GBSA binding free energy values (-3.74 kcal/mol and -15.65 kcal/mol, respectively), indicating favorable binding. This ligand (naringenin-4'-O glucuronide) was also the one that produced the highest number of hydrogen bonds in the entire dynamic period (average = 4601 bonds per nanosecond). Six mutant amino acid residues formed these hydrogen bonds from the RBD region of S1 in the Omicron variant: Asn417, Ser494, Ser496, Arg403, Arg408, and His505. Naringenin-4'-O-glucuronide showed promising results as a potential drug candidate against COVID-19. In vitro and preclinical studies are needed to confirm these findings.Communicated by Ramaswamy H. Sarma.

Status and Future Scope of Soft Nanoparticles-Based Hydrogel in Wound Healing.

Wounds are alterations in skin integrity resulting from any type of trauma. The healing process is complex, involving inflammation and reactive oxygen species formation. Therapeutic approaches for the wound healing process are diverse, associating dressings and topical pharmacological agents with antiseptics, anti-inflammatory, and antibacterial actions. Effective treatment must maintain occlusion and moisture in the wound site, suitable capacity for the absorption of exudates, gas exchange, and the release of bioactives, thus stimulating healing. However, conventional treatments have some limitations regarding the technological properties of formulations, such as sensory characteristics, ease of application, residence time, and low active penetration in the skin. Particularly, the available treatments may have low efficacy, unsatisfactory hemostatic performance, prolonged duration, and adverse effects. In this sense, there is significant growth in research focusing on improving the treatment of wounds. Thus, soft nanoparticles-based hydrogels emerge as promising alternatives to accelerate the healing process due to their improved rheological characteristics, increased occlusion and bioadhesiveness, greater skin permeation, controlled drug release, and a more pleasant sensory aspect in comparison to conventional forms. Soft nanoparticles are based on organic material from a natural or synthetic source and include liposomes, micelles, nanoemulsions, and polymeric nanoparticles. This scoping review describes and discusses the main advantages of soft nanoparticle-based hydrogels in the wound healing process. Herein, a state-of-the-art is presented by addressing general aspects of the healing process, current status and limitations of non-encapsulated drug-based hydrogels, and hydrogels formed by different polymers containing soft nanostructures for wound healing. Collectively, the presence of soft nanoparticles improved the performance of natural and synthetic bioactive compounds in hydrogels employed for wound healing, demonstrating the scientific advances obtained so far.

A multivariate analysis of risk factors associated with death by Covid-19 in the USA, Italy, Spain, and Germany.

Aim: Our aim was to investigate the risk factors associated with death from COVID-19 in four countries: The USA, Italy, Spain, and Germany. Subject and methods: We used data from the Institute for Health Metrics and Evaluation with projection information from January-August 2020. A multivariate analysis of logistic regression was performed. The following factors were analyzed (per day): number of beds needed for the hospital services, number of intensive care units (ICU) beds required, number of ventilation devices, number of both hospital and ICU admissions due to COVID-19. Nagelkerke's R2 coefficient of determination was used to evaluate the model's predictive ability. The quality of the model's fit was assessed by the Hosmer-Lemeshow and the chi-square tests. Results: Among the evaluated countries, Italy presented greater need for ICU beds/day (≤ 98; OR = 2315.122; CI 95% [334.767-16,503.502]; p < 0.001) and daily ventilation devices (≤ 118; OR = 1784.168; CI 95% [250.217-12,721.995]; p < 0.001). It is expected that both Italy and Spain have a higher ICU admission rate due to COVID-19 (n = 14/day). Spain will need more beds/day (≤ 357; OR = 146.838; CI 95% [113.242-190.402]; p  < 0.001) and probably will have a higher number of daily hospital admissions (n = 48/day). All the above-mentioned factors have an important impact on patients' mortality due to COVID-19 in all four countries. Conclusions: Further investments in hospitals' infrastructure, as well as the development of innovative devices for patient's ventilation, are paramount to fight the pandemic in the USA, Italy, Spain, and Germany.

Diagnosis and prediction of COVID-19 severity: can biochemical tests and machine learning be used as prognostic indicators?

OBJECTIVE: This study aimed to implement and evaluate machine learning based-models to predict COVID-19' diagnosis and disease severity. METHODS: COVID-19 test samples (positive or negative results) from patients who attended a single hospital were evaluated. Patients diagnosed with COVID-19 were categorised according to the severity of the disease. Data were submitted to exploratory analysis (principal component analysis, PCA) to detect outlier samples, recognise patterns, and identify important variables. Based on patients' laboratory tests results, machine learning models were implemented to predict disease positivity and severity. Artificial neural networks (ANN), decision trees (DT), partial least squares discriminant analysis (PLS-DA), and K nearest neighbour algorithm (KNN) models were used. The four models were validated based on the accuracy (area under the ROC curve). RESULTS: The first subset of data had 5,643 patient samples (5,086 negatives and 557 positives for COVID-19). The second subset included 557 COVID-19 positive patients. The ANN, DT, PLS-DA, and KNN models allowed the classification of negative and positive samples with >84% accuracy. It was also possible to classify patients with severe and non-severe disease with an accuracy >86%. The following were associated with the prediction of COVID-19 diagnosis and severity: hyperferritinaemia, hypocalcaemia, pulmonary hypoxia, hypoxemia, metabolic and respiratory acidosis, low urinary pH, and high levels of lactate dehydrogenase. CONCLUSION: Our analysis shows that all the models could assist in the diagnosis and prediction of COVID-19 severity.

Avaliação do nível de percepção dos riscos de infecção pelo SARS-CoV-2 e da acessibilidade a informações sobre a Covid-19 no Brasil / Assessment of the level of perception of the risks of SARS-CoV-2 infection and of the accessibility to information about Covid-19 in Brazil / Evaluación del nivel de percepción de los riesgos de infección por SARSCoV-2 y de la accesibilidad a informaciones sobre la Covid-19 en Brasil

A Covid-19 tem se revelado um problema emergencial de importância mundial. O estudo apresentado neste artigo tem como objetivo discutir a percepção e comunicação da população brasileira sobre os riscos de contrair a doença. Foi conduzido um estudo transversal envolvendo indivíduos adultos maiores de 18 anos residentes em todo o território brasileiro que responderam a um questionário eletrônico (adaptado de Betsch), entre os dias 4 e 15 de maio de 2020, sobre percepção e comunicação dos riscos de infecção pelo coronavírus. No estudo, foram incluídos 1.291 participantes, sendo em sua maioria servidores públicos (56,2%, n=725). Também constituíram maioria os pertencentes ao sexo feminino (62,9%, n=812) e os que têm nível superior (91,5%, n=1181). Já os que residem no estado do Paraná, apesar de representarem menos da metade dos entrevistados (35,9%, n=464), predominaram se comparados aos que habitam nas demais unidades federativas. Grande parte dos participantes tomou conhecimento da pandemia e obteve informações sobre ela a partir de diferentes fontes: entre elas, especialmente televisão (18,9%), sites ou portais de notícias (16,6%), mídias sociais (16,5%), jornais impressos (11,2%), profissionais de saúde (8,9%), familiares e amigos (8%) e mecanismos de pesquisa na internet (6,3%). Em relação ao grau de confiabilidade das fontes de informação, a maioria dos participantes afirmou que tem alta confiança em informações provenientes dos profissionais de saúde (76,1%, n=982) e muitos expressaram baixa confiança em informações provenientes de folhetos (35,3%, n=456), familiares e amigos (46,7%, n=551), mídias sociais (39,7%, n=513) e telefonemas (45,1%, n=582). Com este estudo conclui-se que o nível de percepção e comunicação sobre a Covid-19 entre os que dele participaram é bom. No entanto, futuros estudos com abordagem quali-quantitativa são necessários para melhor aprofundamento do tema.

The Covid-19 has been revealing a public health emergency of global importance. The study presented in this article aims to discuss the perception and communication by the Brazilian population of the risks of contracting that disease. A cross-sectional study involving adults who was at least 18 years old living in Brazilian territory was developed asking them to answer from 4 to 15 May 2020 an electronic questionnaire (adapted from Betsch) about perception and communication of the risks of coronavirus infections. A total of 1,291 participants were included in the study and the most of them were civil servants (56.2%, n=725). Female (62.9%, n=812) and people with higher education (91.5%, n=1181) also comprised more than 50% of the group. Although less than 50% of the total of participants (35.9%, n=464) were residents of the state of Paraná, they predominated when compared to the people who live in the other states. Most participantswere aware of the pandemic and get news about it from different sources of information: especially television (18.9%), websites or portals of news (16.6%), social media (16.5%), newspapers (11.2%), health workforce (8.9%), family and friends (8%) and search engines (6.3%). Regarding the degree of confidence in the sources of information, the most of participants stated that they have high confidence in information given by health workforce (76.1%, n=982) and a great number of them expressed low confidence in information given by leaflets (35.3%, n=456), family and friends (46.7%, n=551), social media (39.7%, n=513) and phone (45.1%, n=582). From this study we could conclude that the level of perception and communication about Covid-19 among their participants is good. However, future studies with a qualitative and quantitative approach are necessary to achieve a profounder understanding of the matter.

La Covid-19 se revela un problema de emergencia de salud pública de importancia mundial. Este artículo presenta un estudio que tiene como objetivo discutir la percepción y comunicación de la población brasileña acerca de los riesgos de contraer esa enfermedad. Ha sido realizado un estudio transversal con personas adultas mayores de 18 años residentes en todo el territorio brasileño que respondieron a un cuestionario electrónico (adaptado de Betsch), entre los días 4 y 15 de mayo, sobre percepción y comunicación de los riesgos de infección por el coronavirus. Se incluyeron en el estudio un total de 1.291 participantes, la mayoría de los cuales era de funcionarios públicos (56,2%, n=725). Mujeres también componían mayoría (62,9%, n=812) así como los que tenían estudios superiores (91,5%, n=1181). Por lo que toca a los residentes del estado de Paraná (35,9%, n=464), aunque no constituyan la mayor parte de los entrevistados, tienen un predominio si comparados con los que residen en el resto del país. Un gran número de participantes tuvieron noticia de la pandemia a través de diferentes fuentes de información: especialmente televisión (18,9%), sitios web o portales de noticias (16,6%), redes sociales (16,5%), periódicos impresos (11,2%), profesionales de la salud (8,9%), familiares y amigos (8%) y motores de búsqueda en internet (6,3%). En cuanto al grado de confianza de las fuentes de información, la mayoría de los participantes manifestó tener alta confianza en la información de los profesionales de la salud (76,1%, n=982) y muchos de ellos expresaron baja confianza en la información por medio de folletos (35,3%, n=456), familiares y amigos (46,7%, n=551), redes sociales (39,7%, n=513) y teléfono (45,1%, n=582). Ese estudio permite concluir que el nivel de percepción y comunicación sobre la Covid-19 entre los participantes es bueno. Sin embargo, son necesarios estudios futuros con un enfoque cualitativo y cuantitativo para comprender mejor el tema.

Development and validation of an UV-Vis spectrophotometric method for the quantification of oclacitinib in capsule formulation

Objective. The aim of this study was the development and validation of an UV-Vis spectrophotometric method for the quantification of oclacitinib in commercial capsule formulation since pharmacopeias have not yet provided an official monograph for this drug. Methods. The parameters linearity, limit of detection, limit of quantitation, specificity, precision, accuracy, and robustness were determined according to Brazilian and international guidelines. Results. Linearity was determined for the analytical range of 5-15 µg/mL, and a limit of detection of 1.18 µg/mL and limit of quantification of 3.58 µg/mL were obtained. The method was selective and the precision was demonstrated through repeatability and intermediate precision, with relative standard deviations of 1.96% and 1.78%, respectively. In its turn, accuracy presented recovery percentages of 98.32-100.91%. All robustness and sample stability (48 h at 25 °C) results revealed no statistical variation among the groups. Conclusions. The presented method is suitable for the quantification of oclacitinib in commercial capsule formulation.

Risk factors associated with delay in diagnosis and mortality in patients with COVID-19 in the city of Rio de Janeiro, Brazil.

We investigated the predictors of delay in the diagnosis and mortality of patients with COVID-19 in Rio de Janeiro, Brazil. A cohort of 3,656 patients were evaluated (Feb-Apr 2020) and patients' sociodemographic characteristics, and social development index (SDI) were used as determinant factors of diagnosis delays and mortality. Kaplan-Meier survival analyses, time-dependent Cox regression models, and multivariate logistic regression analyses were conducted. The median time from symptoms onset to diagnosis was eight days (interquartile range [IQR] 7.23-8.99 days). Half of the patients recovered during the evaluated period, and 8.3% died. Mortality rates were higher in men. Delays in diagnosis were associated with male gender (p = 0.015) and patients living in low SDI areas (p < 0.001). The age groups statistically associated with death were: 70-79 years, 80-89 years, and 90-99 years. Delays to diagnosis greater than eight days were also risk factors for death. Delays in diagnosis and risk factors for death from COVID-19 were associated with male gender, age under 60 years, and patients living in regions with lower SDI. Delays superior to eight days to diagnosis increased mortality rates.

Risk factors associated with delay in diagnosis and mortality in patients with COVID-19 in the city of Rio de Janeiro, Brazil / Fatores de risco associados ao atraso no diagnóstico e mortalidade em pacientes com COVID-19 na cidade do Rio de Janeiro, Brasil

Abstract We investigated the predictors of delay in the diagnosis and mortality of patients with COVID-19 in Rio de Janeiro, Brazil. A cohort of 3,656 patients were evaluated (Feb-Apr 2020) and patients' sociodemographic characteristics, and social development index (SDI) were used as determinant factors of diagnosis delays and mortality. Kaplan-Meier survival analyses, time-dependent Cox regression models, and multivariate logistic regression analyses were conducted. The median time from symptoms onset to diagnosis was eight days (interquartile range [IQR] 7.23-8.99 days). Half of the patients recovered during the evaluated period, and 8.3% died. Mortality rates were higher in men. Delays in diagnosis were associated with male gender (p = 0.015) and patients living in low SDI areas (p < 0.001). The age groups statistically associated with death were: 70-79 years, 80-89 years, and 90-99 years. Delays to diagnosis greater than eight days were also risk factors for death. Delays in diagnosis and risk factors for death from COVID-19 were associated with male gender, age under 60 years, and patients living in regions with lower SDI. Delays superior to eight days to diagnosis increased mortality rates.

Resumo Investigamos os preditores de atraso no diagnóstico e mortalidade de pacientes com COVID-19 no Rio de Janeiro, Brasil. Uma coorte de 3.656 pacientes foi avaliada (fevereiro-abril de 2020) e as características sociodemográficas dos pacientes, o bairro e o índice de desenvolvimento social (IDS) foram usados como fatores determinantes dos atrasos no diagnóstico e da mortalidade. Foram realizadas análises de sobrevivência de Kaplan-Meier, modelos de regressão Cox dependentes do tempo e análises de regressão logística multivariada. O tempo mediano desde o início dos sintomas até o diagnóstico foi de oito dias (intervalo interquartil [IQR] 7,23-8,99 dias). Metade dos pacientes se recuperou no período avaliado e 8,3% faleceram. As taxas de mortalidade foram maiores nos homens. Atrasos no diagnóstico foram associados ao sexo masculino (p = 0,015) e pacientes que moravam em áreas com baixo IDS (p < 0,001). As faixas etárias estatisticamente associadas à morte foram: 70-79 anos, 80-89 anos e 90-99 anos. Atrasos no diagnóstico superiores a oito dias também foram fatores de risco para óbito. Atrasos no diagnóstico e fatores de risco para morte por COVID-19 foram associados ao sexo masculino, idade abaixo de 60 anos e pacientes que vivem em regiões com menor IDS. Atrasos superiores a oito dias no diagnóstico aumentam as taxas de mortalidade.