Preoperative activation of the renin-angiotensin system and myocardial injury in noncardiac surgery: exploratory mechanistic analysis of the SPACE randomised controlled trial.

Background: Hypertension therapy in older adults is often suboptimal, in part because of inadequate suppression of the renin-angiotensin-aldosterone system (RAAS). We hypothesised that distinct endotypes of RAAS activation before noncardiac surgery are associated with increased risk of myocardial injury.

Methods: This was a prespecified exploratory analysis of a multicentre randomised controlled trial (ISRCTN17251494) which randomised patients ≥60 yr old undergoing elective noncardiac surgery to either continue or stop RAAS inhibitors (determined by pharmacokinetic profiles).

Chronic pain: a modifiable target to reduce perioperative cardiovascular morbidity.

Recent epidemiological studies suggest that chronic pain is a clinically under-recognised cause for cardiovascular morbidity and mortality. Up to 30% of patients undergoing surgery report chronic pain, but the impact of pre-existing pain on postoperative cardiovascular outcomes is not known. Chronic pain and cardiovascular dysfunction share fundamental pathological mechanisms.

Can the AMOEBA forcefield be used for high pressure simulations? The extreme case of methane and water.

We have performed classical molecular dynamics simulations using the fully polarizable Atomic Multipole Optimized Energetics for Biomolecular Applications (AMOEBA) forcefield implemented within the Tinker package to determine whether a more adequate treatment of electrostatics is sufficient to correctly describe the mixing of methane with water under high pressure conditions. We found a significant difference between the ability of AMOEBA and other classical, computationally cheaper forcefields, such as TIP3P, simple point charge-extended, TIP4P, and optimized potentials for liquid simulations-all atom. While the latter models fail to detect any effect of pressure on the miscibility of methane in water, AMOEBA qualitatively captures the experimental observation of the increased solubility of methane in water with pressure.

Combining models to generate consensus medium-term projections of hospital admissions, occupancy and deaths relating to COVID-19 in England.

Mathematical modelling has played an important role in offering informed advice during the COVID-19 pandemic. In England, a cross government and academia collaboration generated medium-term projections (MTPs) of possible epidemic trajectories over the future 4-6 weeks from a collection of epidemiological models. In this article, we outline this collaborative modelling approach and evaluate the accuracy of the combined and individual model projections against the data over the period November 2021-December 2022 when various Omicron subvariants were spreading across England.