Objective: To assess the variation of effect estimates in the analysis of mortality and length of stay (LOS) in patients with infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Design: Systematic review and meta-analysis Methods: Literature search for clinical studies from 1 January 1960 to 1 October 2018 was conducted in PubMed. Primary outcomes were risk ratios (RRs) of all-cause and attributable mortality and weighted mean differences (WMDs) in LOS in patients with bloodstream infections (BSIs) and non-invasive infections. Any change in the effect estimates was assessed by grouping studies according to design, setting, economy-based country classification, reporting period, microbiological aetiology, infection type and adjustment for appropriateness of empirical treatment. The impact of ESBL production was calculated using random-effect meta-analysis and heterogeneity was evaluated by I² statistics and metaregression. Results: Eighty-four studies including 22 030 patients and 149 outcome measures were included in the meta-analysis. Most studies were retrospective cohorts from high-income countries, providing unadjusted estimates. ESBL production in patients with BSIs (56 studies) increased the RR for all-cause mortality by a factor of 1.70 (95% CI 1.52 to 1.90; p<0.001), attributable mortality (16 studies) by 1.75 (95% CI 1.448 to 2.108; p<0.001) and WMD in the intensive care unit by 3.07 days (95% CI 1.61 to 4.54; p<0.001). WMD in hospital LOS was significantly higher in BSIs (4.41 days; 95% CI 3.37 to 5.46; p<0.001) and non-invasive (2.19 days; 95% CI 1.56 to 2.81; p<0.001). Subgroup analyses showed variation of estimates by study design, population, strain and assessment of appropriateness of empiric treatment. High heterogeneity was observed in all analyses. Conclusions: Current evidence of the clinical burden of infections caused by ESBL-producing bacteria is highly heterogeneous and based mainly on unadjusted estimates derived from retrospective studies. Despite these limitations, ESBL production in strains causing BSIs seems associated with higher all-cause and attributable mortality and longer hospitalisation.

We are in the midst of a pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). SARS-CoV-2 has caused more than two million deaths after one year of the pandemic. The world is experiencing a deep economic recession. Safe and effective vaccines are needed to prevent further morbidity and mortality. Vaccine candidates against COVID-19 have been developed at an unprecedented speed, with more than 200 vaccine candidates currently under investigation. Among those, 20 candidates have entered the clinical Phase 3 to evaluate efficacy, and three have been approved by the European Medicines Agency. The aim of immunization is to act against infection, disease and/or transmission. However, the measurement of vaccine efficacy is challenging, as efficacy trials need to include large cohorts with verum and placebo cohorts. In the future, this will be even more challenging as further vaccine candidates will receive approval, an increasing number of humans will receive vaccinations and incidence might decrease. To evaluate novel and second-generation vaccine candidates, randomized placebo-controlled trials might not be appropriate anymore. Correlates of protection (CoP) could be an important tool to evaluate novel vaccine candidates, but vaccine-induced CoP have not been clearly defined for SARS-CoV-2 vaccines. In this review, we report on immunogenicity against natural SARS-CoV-2 infection, vaccine-induced immune responses and discuss immunological markers that can be linked to protection. By discussing the immunogenicity and efficacy of forerunner vaccines, we aim to give a comprehensive overview of possible efficacy measures and CoP.

Heatwaves are becoming more common and impact health. We conducted a representative survey in June 2022 in Germany to determine people’s knowledge and protective behaviours on heat days. In data from 953 respondents, we found that a large proportion informed themselves about upcoming heat days, but there are considerable gaps in knowledge. While knowledge was not related to taking up protecting behaviour, other predictors were (e.g. risk perception). Health campaigns should therefore not only aim to improve knowledge but also address risk perceptions, facilitate social learning, communicate social norms and remove barriers that prevent protective behaviours.

The development of an effective vaccine against SARS-CoV-2 marks one of the highest priorities during the ongoing pandemic. However, recruitment of participants for clinical trials can be challenging, and recruitment failure is among the most common reasons for discontinuation in clinical trials. From 20 May 2020, public announcements about a planned phase I trial of the vaccine candidate MVA-SARS-2-S against SARS-CoV-2 began, and interested individuals started contacting the study team via designated e-mail. All emails received from these individuals between 20 May 2020–30 September 2020 were assessed. Of the 2541 interested volunteers, 62% contacted the study team within three days after the first media announcement. The average age was 61 years (range 16–100), 48% of volunteers were female and 52% male. A total of 274, 186, and 53 individuals, respectively, reported medical pre-conditions, were health-care workers, or had frequent inter-person contacts. In conclusion, we report a high number of volunteers, with a considerable percentage stating factors for an elevated risk to acquire COVID-19 or develop severe disease. Factors such as media coverage and the perception of a disease as an acute threat may influence the individual’s choice to volunteer for a vaccine trial. Our data provide first important insights to better understand reasons to participate in such trials to facilitate trial implementation and recruitment.

Misinformation and media reports about critical events in vaccine trials challenge public confidence in Covid-19 vaccine safety. Three online experiments using 2×2 between-subjects designs examined the impact of vaccine type, misinformation debunking, and critical events during vaccine trials. In Experiment 1, N = 984 participants received information about different vaccines and misinformation was debunked. In Experiment 2, N = 1,018 participants were informed about different vaccines and trial discontinuation. In Experiment 3, N = 1,006 participants received information about discontinuation and questionable research practices of a manufacturer. The main dependent variables were confidence in vaccine safety, vaccination intention, and willingness to participate in a vaccine trial. Debunking increased vaccination intention and confidence (both η²_p = .01) which was partly higher for classical than for new vaccines (η²_p = .01). Information about discontinuation had no effect, but having heard about it before had benefits. Information about questionable research practices decreased confidence ( η²_p = .01) and vaccination intention ( η²_p = .02) regarding the target vaccine but did not affect other vaccines. Confidence (β = .47) was most strongly associated with willingness to participate in vaccine trials. Critical events in vaccine trials should be communicated transparently to increase confidence, trial participation, and vaccination intentions.

Vaccine effectiveness and safety concerns can prevent people from receiving their first Covid-19 vaccines or boosters. Understanding the vaccine mechanism may lead people to perceive vaccine effectiveness appropriately. This study tested whether helping people understand the vaccine’s mechanism could improve their perceived vaccine safety and effectiveness. In a preregistered study, N = 1,548 unvaccinated or non-boosted participants were randomly presented with one of three communication formats: a fact box (a benefit-risk profile in tabular format; control condition), an expository text (i.e., a purely factual explanation) plus fact box, or an analogy plus fact box. Participants rated the vaccine’s effectiveness in preventing a Covid-19 disease, their perceived risk of getting vaccinated, and their intention to get vaccinated or boosted (depending on their vaccination status). Reading either additional text about the vaccines’ mechanism increased participants’ effectiveness ratings for the vaccine to prevent Covid-19 but did not affect risk ratings or vaccination intentions. The participants’ vaccine-related perceptions and intentions did not differ between the two text types. Elaborating on the vaccine’s mechanism of protection, in addition to presenting the benefit-risk profile of a vaccine, can lead people to perceive the vaccine effectiveness as slightly higher, yet it is insufficient to increase vaccination intentions.