Perception of pharmacological prevention and subsequent non-adherence to medication in patients with ischaemic heart disease: a population-based cohort study

ObjectiveA patient-focused approach is advocated to embody risk of non-adherence to medication and subsequent adverse clinical outcomes following ischaemic heart disease (IHD). This study aimed to explore how patient perceived information on pharmacological prevention was associated with subsequent non-adherence to medication (measured by non-initiation, non-implementation and non-persistence) in patients with incident IHD.DesignCohort study.SettingDenmark.ParticipantsRegister-based cohort of 829 patients with incident IHD in 2013.MeasuresPerception covered whether patients’ experienced being adequately informed about their pharmacological prevention. Information on such was obtained from a survey and divided into ‘Well informed’, ‘Moderately informed’ and ‘Poorly informed’. Information on baseline characteristics, and reimbursed prescriptions of medication (antiplatelets, statins, ACE-inhibitors/angiotensin receptor blockers and β-blockers) during follow-up were obtained by linkage to nationwide public registers. Non-initiation and non-implementation of medication, measured as proportion of days covered, were analysed by Poisson regression. Non-persistence to medication, measured as risk of discontinuation, was analysed by multivariable Cox proportional hazard regression.Primary and secondary outcome measuresNon-implementation and non-persistence to medication up to 365 days of follow-up were primary outcomes. Secondary outcomes included non-initiation as well as non-implementation and non-persistence to medication at 180 days of follow-up.ResultsA dose–response association was in general found between perception of pharmacological prevention and risk of non-implementation and non-persistence. For example, the hazard of non-persistence to antiplatelets was 1.18 (95% CI 0.71 to 1.96) times higher for patients reporting 'Moderately informed' and 1.89 (95% CI 1.10 to 3.25) times higher for patients reporting 'Poorly informed', compared with patients reporting 'Well informed of perception of pharmacological prevention' up to 365 days of follow-up.ConclusionLower levels of perception of pharmacological prevention were associated with subsequent non-implementation and non-persistence to medication in patients with incident IHD.

New variants of SARS-CoV-2, vaccine immune response and the Brazilian reality

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly pathogenic β-coronavirus, is the etiologic agent of coronavirus disease 2019 (COVID-19), which gave rise to a difficult to control pandemic, especially in Brazil. Approximately 4,000 mutations have been identified in SARS-CoV-2, with the majority being redundant without having any biological effect on the virus. The aim of the present study was to objectively understand how new SARS-CoV-2 variants can affect vaccine response, in addition to highlighting the current situation in Brazil in the face of the pandemic and considering epidemiological and immunological aspects of COVID-19. The main protective correlate investigated in most vaccines is the neutralizing antibody titer induced by immunizing agents, observed in the pre-clinical phase in animals, whose action is to block the binding of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor, preventing infection. Up to the second half of 2021, the variants that are of greatest concern worldwide and require molecular surveillance are Alpha variant (or B.1.1.7 lineage), Beta (or B.1.351 lineage), Gamma (or P1 lineage) and Delta (or B.1.617.2 lineage). Brazil finds itself in a highly unfavorable scenario, with the circulation of variants of concern, mainly Gamma and Delta, with high fatality rates for COVID-19 and low vaccination rate. Given the still latent situation of the COVID-19 pandemic in Brazil, the lack of global planning for action strategies for non-pharmacological prevention measures, there is an imminent risk of the emergence of new variants due to the finding of susceptible hosts and the high proliferative rate of SARS-CoV-2. It is urgent to increase the genotyping of positive samples isolated from infected individuals, the speed of vaccination of the entire population and the unification of non pharmacological preventive measures throughout the country.

Epidemiological perspective of the evolution of the COVID-19 pandemic in Amapá State, Northern Brazil

Introduction: COVID-19 impacted health systems worldwide; the virus quickly spread in Brazil, reaching the 27 Federative units in Brazil peculiarly. The northern region of Brazil recorded the lowest number of cases and accumulated deaths from the disease. However, it is a region of sizeable territorial extension and low demographic density, marked by socioeconomic inequalities and vulnerable groups, such as indigenous tribes, riverine peoples, and quilombolas. Sociodemographic factors may contribute to the dissemination of the coronavirus in the region; thus, studies are needed to analyze the epidemiological indicators related to the pandemic. Objective: to evaluate incidence, mortality, and case fatality of COVID-19 trends in the state of Amapá, Brazil, from March 2020 to April 2021. Methods: an ecological time-series study was conducted with publicly accessible data from the Health Department of the State of Amapá. Incidence and mortality rates per 100,000 inhabitants and percentage case fatality were calculated. Crude rates were calculated by municipalities, age, and sex, per month. The Prais-Winsten regression test was performed, and the trends of monthly rates were classified as increasing, decreasing, or flat. Results: during the study period, there were 99.936 cases and 1,468 deaths accumulated by COVID-19 in the State of Amapá, Brazil. Macapá and Santana’s cities, which have the highest demographic density and Human Development Index (HDI), had the highest number of cases and deaths. The most vulnerable population was elderly males aged 70 years or over; these individuals had the highest cumulative incidence, case fatality, and mortality rates. The second wave of the disease (October 2020 to April 2021) illustrated a more aggravating scenario, with increasing incidence and mortality rates. Conclusion: the COVID-19 pandemic in the state of Amapá, Brazil, is in increasing evolution, which illustrates that non-pharmacological prevention measures and acceleration of vaccination must be strengthened to avoid the development of future waves of the disease.

Involvement of trabecular meshwork phagocytic suppression by sympathetic norepinephrine in nocturnal intraocular pressure rise

Intraocular pressure (IOP) is important in glaucoma development and depends on aqueous humor (AH) dynamics, involving inflow from the ciliary body and outflow through the trabecular meshwork (TM). IOP has a circadian rhythm entrained by sympathetic noradrenaline (NE) or adrenal glucocorticoids (GCs). Here, we investigated the involvement of GC and NE in AH outflow. Pharmacological prevention of inflow/outflow in mice indicated an AH outflow increase during day. Although TM phagocytosis can determine AH drainage, only NE showed a non-self-sustained inhibitory effect in phagocytosis of immortalized human TM cells. Pharmacological approach and RNA interference identified β1-adrenergic receptor (AR)-mediated cAMP-EPAC-SHIP1 signal activation by ablation of phosphatidylinositol triphosphate regulating phagocytic cup formation. Furthermore, pharmacological instillation in mice revealed the role of β1-AR-EPAC-SHIP1 pathway in nocturnal IOP rise. These suggest that IOP rhythm is partially regulated by this pathway. This first demonstration of TM phagocytosis suppression by NE could be useful in glaucoma management.

Inflammatory Bowel Disease and Risk of Colorectal Cancer: An Overview From Pathophysiology to Pharmacological Prevention

Increased risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients has been attributed to long-standing chronic inflammation, with the contribution of genetic alterations and environmental factors such as the microbiota. Moreover, accumulating data indicate that IBD-associated CRC (IBD-CRC) may initiate and develop through a pathway of tumorigenesis distinct from that of sporadic CRC. This mini-review summarizes the current knowledge of IBD-CRC, focusing on the main mechanisms underlying its pathogenesis, and on the important role of immunomodulators and biologics used to treat IBD patients in interfering with the inflammatory process involved in carcinogenesis.

Influence of meteorological factors on the occurrence of bleeding from varicose veins of the esophagus

BACKGROUND: The problem of liver cirrhosis and associated bleedings from the varicose veins of the esophagus, unfortunately, remains highly relevant for Russia. Undoubtedly, it is important to identify factors that provoke an episode of bleeding. From a practical point of view, the most interesting ones are those that have an easily detectable nature and the maximum possible predictability. One of these factors, which is constantly varying throughout the year, is meteorological conditions. AIM: To evaluate the influence of meteorological factors on the occurrence of bleeding from varicose veins of the esophagus and the possibility of using this information to improve the schemes of primary prevention. MATERIALS AND METHODS: The material for the study was the results of examination and treatment of 86 patients hospitalized in 2016–2018 at the Emergency Hospital of Ryazan with a diagnosis of bleeding from esophageal varices. All these patients underwent fibroesophago-gastroduodenoscopy upon admission. The analysis of meteorological observations for 2016–2018 was carried out based on information from archived summaries of weather data. The results obtained were statistically processed using a standard set of programs. RESULTS: When analyzing the number of hospitalizations of patients with bleeding from varicose veins of the esophagus in different months of the year, a pronounced unevenness of admissions is revealed, the coefficient of variability is 53.65%. After excluding extreme values from the calculations, it was found that the incidence of the pathology increases in spring and autumn, decreases in summer and winter. The maximum incidence occurs in April and September, and the minimum in July and February. To determine the effect on patients of specific meteorological factors, a meteorological profile for a number of months was created from the archived weather data. In the course of statistical processing of the data, it was found that the only meteorological factor demonstrating a stable strong direct correlation with the number of hospitalizations of patients with bleeding from varicose veins of the esophagus (Pearson's correlation coefficient 0.9449) is the average atmospheric pressure gradient. This fact proves the ability of sudden changes in atmospheric pressure to provoke episodes of bleeding from the veins of the esophagus. CONCLUSIONS: When planning a course of primary pharmacological prevention of bleeding emerging the varicose veins of the esophagus, it is necessary to take into account the morbidity peaks occurring in April and September, as well as the ability of sudden changes of the atmospheric pressure to trigger the bleeding episodes.

Topical transdermal chemoprevention of breast cancer: where will nanomedical approaches deliver us?

Despite the high incidence of breast cancer, there are few pharmacological prevention strategies for the high-risk population and those that are available have low adherence. Strategies that deliver drugs directly to the breasts may increase drug local concentrations, improving efficacy, safety and acceptance. The skin of the breast has been proposed as an administration route for local transdermal therapy, which may improve drug levels in the mammary tissue, due to both deep local penetration and percutaneous absorption. In this review, we discuss the application of nanotechnology-based strategies for the delivery of well established and new agents as well as drug repurposing using the topical transdermal route to improve the outcomes of preventive therapy for breast cancer.