The Circulating Renin-Angiotensin System and Mortality among Patients Hospitalized for COVID-19: A Mechanistic Substudy of the ACTIV-4 Host Tissue Trials.

SARS-CoV-2 targets angiotensin converting enzyme-2 (ACE2), a key peptidase of the renin-angiotensin system (RAS), which regulates the balance of the vasoconstrictor/inflammatory peptide Ang II and the vasodilator/anti-inflammatory peptide Ang-(1-7). Few studies have quantified the circulating elements of the RAS longitudinally in SARS-CoV-2 infection and their association with COVID-19 outcomes. Thus, we evaluated the association of circulating RAS enzymes and peptides with mortality among patients with COVID-19.

Evaluation of a modified venous excess ultrasound (VExUS) protocol for estimation of venous congestion: a cohort study.

Background: Understanding venous congestion is critical to the management of many illnesses, but assessing volume status can be challenging. The current gold standard for volume status assessment of right heart catheterization (RHC) is invasive, costly, and often unavailable. Venous Excess Ultrasound Score (VExUS) is a novel ultrasound protocol for to assessment of venous congestion using the inferior vena cava, hepatic, portal and renal veins.

Core Concepts: Self-Controlled Designs in Pharmacoepidemiology.

One of the key challenges in pharmacoepidemiological studies is that of uncontrolled confounding, which occurs when confounders are poorly measured, unmeasured or unknown. Self-controlled designs can help address this issue, as their key comparison is not between people, but periods of time within the same person. This controls for all time-stable confounders (genetics) and in the absence of time-varying confounding negates the need for an external control group.

Potential interactions between antimicrobials and direct oral anticoagulants: Population-based cohort and case-crossover study.

Background: Although drug interactions between clarithromycin/erythromycin/fluconazole and direct oral anticoagulants (DOACs) are mechanistically plausible, it is uncertain whether they are clinically relevant.

Objective: This study aims to investigate the association among coprescribed DOACs and antimicrobials and bleeding, cardiovascular disease and mortality.

Methods: We identified DOAC users in the Clinical Practice Research Datalink Aurum from January 1, 2011 to March 29, 2021.

Using Quantitative Bias Analysis to Adjust for Misclassification of COVID-19 Outcomes: An Applied Example of Inhaled Corticosteroids and COVID-19 Outcomes.

Background: During the pandemic, there was concern that underascertainment of COVID-19 outcomes may impact treatment effect estimation in pharmacoepidemiologic studies. We assessed the impact of outcome misclassification on the association between inhaled corticosteroids (ICS) and COVID-19 hospitalisation and death in the United Kingdom during the first pandemic wave using probabilistic bias analysis (PBA).

Methods: Using data from the Clinical Practice Research Datalink Aurum, we defined a cohort with chronic obstructive pulmonary disease (COPD) on 1 March 2020.