We were in this prospective randomized proof-of-concept trial, unable to show distinct protective effects of the studied conditioning methods. However, this trial can hopefully contribute to generate a productive discussion concerning limitations and future use of cardiac conditioning as well as microdialysis technique.

Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.

Objectives After transcatheter aortic valve implantation (TAVI) has been available for high-risk patients with severe aortic valve stenosis (AVS), the decision-making of the Heart Team (HT) has not been examined. Design All adult patients with severe AVS referred to a large tertiary medical centre in 2011 were prospectively included. Multivariate regression analysis identified independent factors associated with treatment decisions. Results A total of 487 patients were included (mean age: 75 years, NYHA class III-IV: 47%). The HT proposed medical therapy (MT) in 35 (7%), TAVI in 60 (12%), and surgical aortic valve replacement (SAVR) in 392 (81%) of patients. In patients referred to intervention, TAVI compared with SAVR patients were older (OR = 1.17 per year, 95% CI 1.09-1.26; p < 0.01) with more previous coronary artery bypass surgery (OR = 385, 79-2738; p < 0.01), obesity (OR = 4.69, 1.51-13.77; p < 0.01), and chronic obstructive pulmonary disease (COPD) (OR = 3.66, 1.21-10.75; p = 0.02). MT patients compared with patients referred to any intervention were older, had a higher prevalence of COPD, peripheral arterial disease, previous myocardial infarction, and cerebrovascular disease. Conclusions The HT proposed intervention in 93% of patients with severe AVS despite high age, advanced symptoms and a high burden of co-morbidity. TAVI was reserved for older patients particularly with previous CABG.

The COVID-19 pandemic burdens hospitals, but consequences for quality of care outcomes such as healthcare-associated infections are largely unknown. This cohort included all adult hospital episodes (n=186 945) at an academic centre between January 2018 and January 2021. Data were collected from the hospitals’ electronic health record data repository. Hospital-onset bloodstream infection (HOB) was defined as any positive blood culture obtained ≥48 hours after admission classified based on microbiological and hospital administrative data. Subgroup analyses were performed with exclusion of potential contaminant bacteria. The cohort was divided into three groups: controls (prepandemic period), non-COVID-19 (pandemic period) and COVID-19 (pandemic period) based on either PCR-confirmed SARS-CoV-2 infections from respiratory samples or International Classification of Diseases 10th Revision diagnoses U071 and U72 at discharge. Adjusted incidence rate ratios (aIRR) and risk of death in patients with HOB were compared between the prepandemic and pandemic periods using Poisson and logistic regression. The incidence of HOB was increased for the COVID-19 group compared with the prepandemic period (aIRR 3.34, 95% CI 2.97 to 3.75). In the non-COVID-19 group, the incidence was slightly increased compared with prepandemic levels (aIRR 1.20, 95% CI 1.08 to 1.32), but the difference decreased when excluding potential contaminant bacteria (aIRR 1.15, 95% CI 1.00 to 1.31, p=0.04). The risk of dying increased for both the COVID-19 group (adjusted odds ratio (aOR) 2.44, 95% CI 1.75 to 3.38) and the non-COVID-19 group (aOR 1.63, 95% CI 1.22 to 2.16) compared with the prepandemic controls. These findings were consistent also when excluding potential contaminants. In summary, we observed a higher incidence of HOB during the COVID-19 pandemic, and the mortality risk associated with HOB was greater, compared with the prepandemic period. Results call for specific attention to quality of care during the pandemic.