Relational conflicts during COVID-19: Impact of loss and reduction of employment due to prevention measures and the influence of sex and stress (in the iCARE study).

This study explored the association between pandemic-related loss/reduction of employment, sex, COVID-19-related stress and relational conflicts. A sample of 5103 Canadians from the iCARE study were recruited through an online polling firm between October 29, 2020, and March 23, 2021. Logistic regressions revealed that participants with loss/reduction of employment were 3.6 times more likely to report increased relational conflicts compared to those with stable employment (OR = 3.60; 95% CIs = 3.03-4.26). There was a significant interaction between employment status and sex (x2 = 10.16; p < 0.005), where loss/reduction of employment was associated with more relational conflicts in males compared to females. There was a main effect of COVID-19-related stress levels on relational conflicts (increased stress vs no stress : OR = 9.54; 95% CIs = 6.70-13.60), but no interaction with loss/reduction of employment (x2 = 0.46, p = 0.50)

Understanding national trends in COVID-19 vaccine hesitancy in Canada: results from five sequential cross-sectional representative surveys spanning April 2020–March 2021

Objective: To examine rates of vaccine hesitancy and their correlates among Canadian adults between April 2020 and March 2021. Design: Five sequential cross-sectional age, sex and province-weighted population-based samples who completed online surveys. Setting: Canada. Participants: A total of 15 019 Canadians aged 18 years and over were recruited through a recognised polling firm (Leger Opinion). Respondents were 51.5% female with a mean age of 48.1 (SD 17.2) years (range 18–95 years) and predominantly white (80.8%). Primary and secondary outcome measures: Rates of vaccine hesitancy over the five surveys (time points) and their sociodemographic, clinical and psychological correlates. Results: A total of 42.2% of respondents reported some degree of vaccine hesitancy, which was lowest during surveys 1 (April 2020) and 5 (March 2021) and highest during survey 3 (November 2020). Fully adjusted multivariate logistic regression analyses revealed that women, those aged 50 and younger, non-white, those with high school education or less, and those with annual household incomes below the poverty line in Canada were significantly more likely to report vaccine hesitancy, as were essential and healthcare workers, parents of children under the age of 18 and those who do not get regular influenza vaccines. Endorsing prevention behaviours as important for reducing virus transmission and high COVID-19 health concerns were associated with 77% and 54% reduction in vaccine hesitancy, respectively. Having high personal financial concerns was associated with 1.33 times increased odds of vaccine hesitancy. Conclusions: Results highlight the importance of targeting vaccine efforts to specific groups by emphasising the outsized health benefits compared with risks of vaccination. Future research should monitor changes in vaccine intentions and behaviour to better understand underlying factors

Modulation of epithelial sodium channel (ENaC) expression in mouse lung infected with Pseudomonas aeruginosa

BACKGROUND: The intratracheal instillation of Pseudomonas aeruginosa entrapped in agar beads in the mouse lung leads to chronic lung infection in susceptible mouse strains. As the infection generates a strong inflammatory response with some lung edema, we tested if it could modulate the expression of genes involved in lung liquid clearance, such as the α, β and γ subunits of the epithelial sodium channel (ENaC) and the catalytic subunit of Na(+)-K(+)-ATPase. METHODS: Pseudomonas aeruginosa entrapped in agar beads were instilled in the lung of resistant (BalB/c) and susceptible (DBA/2, C57BL/6 and A/J) mouse strains. The mRNA expression of ENaC and Na(+)-K(+)-ATPase subunits was tested in the lung by Northern blot following a 3 hours to 14 days infection. RESULTS: The infection of the different mouse strains evoked regulation of α and β ENaC mRNA. Following Pseudomonas instillation, the expression of αENaC mRNA decreased to a median of 43% on days 3 and 7 after infection and was still decreased to a median of 45% 14 days after infection (p < 0.05). The relative expression of βENaC mRNA was transiently increased to a median of 241%, 24 h post-infection before decreasing to a median of 43% and 54% of control on days 3 and 7 post-infection (p < 0.05). No significant modulation of γENaC mRNA was detected although the general pattern of expression of the subunit was similar to α and β subunits. No modulation of α(1)Na(+)-K(+)-ATPase mRNA, the catalytic subunit of the sodium pump, was recorded. The distinctive expression profiles of the three subunits were not different, between the susceptible and resistant mouse strains. CONCLUSIONS: These results show that Pseudomonas infection, by modulating ENaC subunit expression, could influence edema formation and clearance in infected lungs

Central nervous system myeloid cells as drug targets: current status and translational challenges

Myeloid cells of the central nervous system (CNS), which include parenchymal microglia, macrophages at CNS interfaces and monocytes recruited from the circulation during disease, are increasingly being recognized as targets for therapeutic intervention in neurological and psychiatric diseases. The origin of these cells in the immune system distinguishes them from ectodermal neurons and other glia and endows them with potential drug targets distinct from classical CNS target groups. However, despite the identification of several promising therapeutic approaches and molecular targets, no agents directly targeting these cells are currently available. Here, we assess strategies for targeting CNS myeloid cells and address key issues associated with their translation into the clinic

Vorapaxar in the secondary prevention of atherothrombotic events

Item does not contain fulltextBACKGROUND: Thrombin potently activates platelets through the protease-activated receptor PAR-1. Vorapaxar is a novel antiplatelet agent that selectively inhibits the cellular actions of thrombin through antagonism of PAR-1. METHODS: We randomly assigned 26,449 patients who had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease to receive vorapaxar (2.5 mg daily) or matching placebo and followed them for a median of 30 months. The primary efficacy end point was the composite of death from cardiovascular causes, myocardial infarction, or stroke. After 2 years, the data and safety monitoring board recommended discontinuation of the study treatment in patients with a history of stroke owing to the risk of intracranial hemorrhage. RESULTS: At 3 years, the primary end point had occurred in 1028 patients (9.3%) in the vorapaxar group and in 1176 patients (10.5%) in the placebo group (hazard ratio for the vorapaxar group, 0.87; 95% confidence interval [CI], 0.80 to 0.94; P<0.001). Cardiovascular death, myocardial infarction, stroke, or recurrent ischemia leading to revascularization occurred in 1259 patients (11.2%) in the vorapaxar group and 1417 patients (12.4%) in the placebo group (hazard ratio, 0.88; 95% CI, 0.82 to 0.95; P=0.001). Moderate or severe bleeding occurred in 4.2% of patients who received vorapaxar and 2.5% of those who received placebo (hazard ratio, 1.66; 95% CI, 1.43 to 1.93; P<0.001). There was an increase in the rate of intracranial hemorrhage in the vorapaxar group (1.0%, vs. 0.5% in the placebo group; P<0.001). CONCLUSIONS: Inhibition of PAR-1 with vorapaxar reduced the risk of cardiovascular death or ischemic events in patients with stable atherosclerosis who were receiving standard therapy. However, it increased the risk of moderate or severe bleeding, including intracranial hemorrhage. (Funded by Merck; TRA 2P-TIMI 50 ClinicalTrials.gov number, NCT00526474.)