The incidence of infections caused by bacteria that are resistant to antibiotics is constantly increasing. In Europe alone, it has been estimated that each year about 33'000 deaths are attributable to such infections. One important driver of antimicrobial resistance is the use and abuse of antibiotics in human medicine. Inappropriate prescribing of antibiotics is still very frequent: up to 50% of all antimicrobials prescribed in humans might be unnecessary and several studies show that at least 50% of antibiotic treatments are inadequate, depending on the setting. Possible strategies to optimize antibiotic use in everyday clinical practice and to reduce the risk of inducing bacterial resistance include: the implementation of rapid microbiological diagnostics for identification and antimicrobial susceptibility testing, the use of inflammation markers to guide initiation and duration of therapies, the reduction of standard durations of antibiotic courses, the individualization of antibiotic therapies and dosing considering pharmacokinetics/pharmacodynamics targets, and avoiding antibiotic classes carrying a higher risk for induction of bacterial resistance. Importantly, measures to improve antibiotic prescribing and antibiotic stewardship programs should focus on facilitating clinical reasoning and improving prescribing environment in order to remove any barriers to good prescribing.

Polypharmacy and inappropriate medication prescriptions are associated with increased morbidity and mortality. Most interventions proposed to improve appropriate prescribing are time and resource intensive and therefore hardly applicable in daily clinical practice. To test the efficacy of an easy-to-use checklist aimed at supporting the therapeutic reasoning of physicians in order to reduce inappropriate prescribing and polypharmacy. We assessed the efficacy and safety of a 5-point checklist to be used by all physicians on the internal medicine wards of a Swiss hospital by comparing outcomes in 450 consecutive patients aged ≥65 years hospitalized after the introduction of the checklist, and in 450 consecutive patients ≥65 years hospitalized before the introduction of the checklist. The main measures were the proportion of patients with prescription of potentially inappropriate medications (PIMs) at discharge, according to STOPP criteria, and the number of prescribed medications at discharge, before and after the introduction of the checklist. Secondary outcomes were the prevalence of polypharmacy (≥ 5 drugs) and hyperpolypharmacy (≥ 10 drugs), and the prevalence of potentially inappropriate prescribing omissions (PPOs) according to START criteria. At admission 59% of the 900 patients were taking > 5 drugs, 13% ≥ 10 drugs, 37% had ≥ 1 PIM and 25% ≥ 1 PPO. The introduction of the checklist was associated with a significant reduction by 22% of the risk of being prescribed ≥ 1 PIM at discharge (adjusted risk ratios [RR] 0.78; 95% CI: 0.68–0.94), but not with a reduction of at least 20% of the number of drugs prescribed at discharge, nor with a reduction of the risk of PPOs at discharge. The introduction of an easy-to-use 5-point checklist aimed at supporting therapeutic reasoning of physicians on internal medicine wards significantly reduced the risk of prescriptions of inappropriate medications at discharge.

Background: Arterial stiffness as assessed by Pulse Wave Velocity (PWV) represents an independent predictor of cardiovascular disease. Several dietary compounds and lifestyle factors could influence arterial stiffness. The debate on the significance of the correlation between alcohol consumption and arterial stiffness is still open, given that the relationship is complex and potentially affected by several factors such as alcohol type, consumption levels, gender and age differences. Objective: This systematic literature review aims to examine the evidence supporting an association between alcohol use and PWV, in electronic databases including PubMed/MEDLINE and the Cochrane Library, from January 2010 to November 2020. Screening and full-text reviews were performed by three investigators and data extraction by two. Considering the significant heterogeneity of data only a qualitative analysis (systematic review) was performed. Results: A total of 13 studies met the inclusion criteria. Alcohol consumption was independently associated with arterial stiffness in a J-shaped way in most of the studies included. A benefit of alcohol consumption on arterial stiffness was found in four experimental studies, whilst an unfavorable increasing linear association was found in four others. Associations were confirmed with both oscillometric and tonometric PWV assessment methods. In some studies, a gender and age correlation was found with a more pronounced association in older males. In all studies elevated levels of alcohol consumption were associated with a worsening of arterial stiffness. Conclusions: Despite the variable findings across studies, the current review provides preliminary evidence that light-to-moderate alcohol consumption is associated with arterial stiffness values lower than expected, and evidence that high doses accelerate arterial ageing. These findings could be useful for clinicians who provide recommendations for patients at cardiovascular (CV) risk. Nevertheless, given the heterogeneity of study designs, interventions, measurement methods and statistical evaluations, the protective role of moderate alcohol consumption on arterial stiffness is likely but not certain, warranting additional trials and evidence.

A variety of antiviral treatments for COVID-19 have been investigated, involving many repurposed drugs. Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive. However, the potential emergence of antiviral resistance poses a threat to the efficacy of any successful therapies on a wide scale. Here, we propose a framework to monitor the emergence of antiviral resistance, and as a proof of concept, we address the interaction between RdRp and remdesivir. We show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare in circulating lineages, and that those mutations, where present, do not destabilise RdRp. In more than 56,000 viral genomes from 105 countries from the first pandemic wave, we found negative selective pressure affecting nsp12 (Tajima’s D = −2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Potential escape mutations included known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations involved globally, in silico structural models found that they were unlikely to be associated with loss of stability in RdRp. No potential escape mutation was found in a local cohort of remdesivir treated patients. Collectively, these findings indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. We anticipate our framework to be the starting point of a larger effort for a global monitoring of drug resistance throughout the COVID-19 pandemic.