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The model highlights the direct and indirect protection benefits when vaccinating healthy children with QLAIV in Belgium. Policies targeting only high-risk individuals or the youngest provide limited herd protection, as school-age children are important influenza vectors in the community.

Objectives: To estimate the public health impact of annual vaccination of children with a quadrivalent live-attenuated influenza vaccine (QLAIV) across Europe. Methods: A deterministic, age-structured, dynamic model was used to simulate influenza transmission across 14 European countries, comparing current vaccination coverage using a quadrivalent inactivated vaccine (QIV) to a scenario whereby vaccination coverage was extended to 50% of 2–17 year-old children, using QLAIV. Differential equations described demographic changes, exposure to infectious individuals, recovery and immunity dynamics. For each country, the basic reproduction number (R0) was calibrated to published influenza incidence statistics. Assumed vaccine efficacy for children was 80% (QLAIV) and 59% (QIV). Symptomatic cases cumulated over 10 years were calculated per 100 000 person-years. One-way sensitivity analyses were conducted on QLAIV efficacy in 7–17 year-olds (59% instead of 80%), durations of natural (±3 years; base case: 6, 12 years for influenza A, B respectively) and QLAIV vaccine-induced immunity (100% immunity loss after 1 season; base case: 30%), and R0 (+/-10% around all-year average value). Results: Across countries, annual QLAIV vaccination additionally prevents 1366–3604 symptomatic cases per 100 000 population (average 2495 /100 000, ie, a reduction of 47.6% of the cases which occur in the reference scenario with QIV vaccination only). Among children (2–17 years), QLAIV prevents 551–1555 cases per 100 000 population (average 990 /100 000, ie, 67.2% of current cases). Among adults, QLAIV indirectly prevents 726-2047 cases per 100 000 population (average 1466 /100 000, ie, 40.0% of current cases). The most impactful drivers of total protection were duration of natural immunity against influenza A, R0 and QLAIV immunity duration and efficacy. In all evaluated scenarios, there was a large direct and even larger indirect protection compared with the reference scenario. Conclusions: The model highlights direct and indirect protection benefits when vaccinating healthy children with QLAIV in Europe, across a range of demographic structures, contact patterns and vaccination coverage rates.

Objectives: To simulate the impact of a pediatric influenza vaccination programme using quadrivalent live attenuated influenza vaccine (QLAIV) in Europe by applying coverage rates achieved in the United Kingdom during the 2014–2015 season and to compare the model outcomes to the UK results. Methods: We used a deterministic, age-structured, dynamic transmission model adapted to the demography, contact patterns and influenza incidence of 13 European countries, with a 10-year horizon. The reference strategy was the unchanged country-specific coverage rate, using quadrivalent inactivated vaccine (assumed efficacy against infection from 45% in 1-year-old children to 60% in healthy adults). In the evaluated strategy, 56.8% of 5–10-year-old children were additionally vaccinated with QLAIV (assumed efficacy 80%), as was the case in 2014–2015 in the United Kingdom’s primary school pilot areas. Symptomatic influenza cases and associated medical resources (primary care consultations [PCC], hospitalization, intensive care unit [ICU] admissions) were calculated. The evaluated versus reference strategies were compared using odds ratios (ORs) for PCC in the target (aged 5–10-years) and non-target adult (aged >17 years) populations as well as number needed to vaccinate (NNV) with QLAIV to avert one PCC, hospitalization or ICU admission. Model outcomes, averaged over 10 seasons, were compared with published real-life data from the United Kingdom for the 2014–2015 season. Results: Over 13 countries and 10 years, the evaluated strategy prevented 32.8 million of symptomatic influenza cases (172.3 vs 205.2 million). The resulting range of ORs for PCC was 0.18–0.48 among children aged 5–10-years, and the published OR in the United Kingdom was 0.06 (95% confidence interval [0.01; 0.62]). In adults, the range of ORs for PCC was 0.60–0.91 (UK OR=0.41 [0.19; 0.86]). NNV ranges were 6–19 per averted PCC (UK NNV=16), 530–1524 per averted hospitalization (UK NNV=317) and 5298–15 241 per averted ICU admission (UK NNV=2205). Conclusions: Across a range of European countries, our model shows the beneficial direct and indirect impact of a paediatric vaccination programme using QLAIV in primary school-aged children, consistent with what was observed during a single season in the United Kingdom. Recommendations for the implementation of pediatric vaccination programmes are, therefore, supported in Europe.

The primary outcome was the mortality within 30 days. Since the clinical characteristics of patients can affect the selection of antibiotics, basic analysis including all subjects who met inclusion and exclusion criteria as well as an analysis using "stabilized Inverse Probability of Treatment Weighting (stabilized IPTW)" that adjusted patient clinical characteristics were conducted. Results: We identified 554 patients who met the eligibility criteria. There was no statistically significant difference in thirty day survival rate between the groups both prior and post to propensity score weighting in empirical treatment. Multivariate analysis of thirty day survival rate conducted after the adjustment of confounding variables affecting mortality rate such as age, infection route, transfer to ICU within 48 hours, infection sites, APACHE II, liver diseases, lung diseases, renal disease and diabetes also revealed that there was no significant difference (HR= 1.01, 95%CI 0.27-3.76). After propensity score weighting, the statistical difference remained insignificant (weighted HR= 0.76, 95%CI 0.23-2.58). There was no statistically significant difference in thirty day survival rate between the groups when carbapenems and BL/BLIs were used as empirical treatment (weighted HR= 0.99, 95%CI 0.29-3.30). cOnclusiOns:The results from this study show that there was no difference in mortality when carbapenems were compared with BL/BLIs alone or with all alternative antibiotics as empirical therapy. Although the role of carbapenems as definitive treatment should be evaluated, considering an increasing carbapenem resistance, alternative antibiotics, such as BL/BLIs, can be used as alternatives for the empirical treatment of patients with ESBL-positive enterobacteriaceae bacteraemia.