205 Summary and general discussion 9 1.74, 95% CI 1.11-2.69, respectively). Because on average, patients that were tested for a viral co-infection were more ill than those who were not tested, inverse probability weighting was used to extrapolate our results from the tested population to the hospital population. In this weighted analysis, the odds for receiving IMV and in-hospital mortality were significantly increased for influenza co-infected patients compared to mono-infected patients (OR 4.32, 95% CI 2.06-9.04, OR 2.49, 95% CI 1.11-5.56, respectively). In this study, influenza and SARS-CoV-2 co-infection was associated with increased risk of receiving IMV and increased risk of in-hospital mortality. With the decrease of preventive non-pharmaceutical measures at the end of the COVID-19 pandemic, such as mask-wearing and social distancing, the risk of co-circulation of different respiratory viruses increases. Therefore, the importance of preventive measures that reduce disease burden, like vaccination, should be emphasised. Similarly, during periods with high incidence of viral respiratory infections, widespread testing for co-infections in hospitalised patients who tested positive for either of the viruses is important, and alternative treatment strategies in co-infected patients could be considered. In Chapter 5, the effectiveness of different IL-6 inhibitors for the treatment of severe COVID-19 was compared, using real-world data from health care insurance claims. IL-6 inhibitors were shown to reduce mortality and the need for invasive mechanical ventilation in multiple large, randomised controlled trials33. IL-6 inhibitors were subsequently recommended for hospitalised patients that have a C-reactive protein of 75 mg/l or higher and who need at least 6 litres/ minute of supplemental oxygen34. Initially, the recommended treatment was 8 mg/kg tocilizumab, but due to the increased demand for IL-6 inhibitors, many countries faced drug shortages35. The recommended treatment was changed from 8 mg/kg to a weight based or fixed dose (600 mg tocilizumab) regimen33. Because of persisting drug shortages, the suggested treatment was changed twice more: first to a fixed dose of 400 mg tocilizumab and finally to 400 mg sarilumab37. This situation, in which the IL-6 treatment regimen was dictated by the timing of hospitalisation, led to a natural experiment, which is an efficient way to study real-world data. Survival was compared in 5485 adult patients treated with IL6 inhibitors who were hospitalised in one of the 49 contributing Dutch hospitals between March 15th, 2021 and December 31st, 2021. After adjustment for confounders, the 8 mg/kg tocilizumab group had a survival benefit compared to the other treatment regimens. The number needed to treat (NNT) was compared between the different treatment regimens using two different scenarios: a no drug shortages scenario and a second scenario in which there were only 500 treatments of 8 mg/kg available, but more if a lower dose would be used. For the first scenario of no drug shortages, the NNT comparing the 8 mg/kg group to the fixed dose 600 mg tocilizumab group was 24, meaning that one life could be saved at day 60 if 24 patients were treated with the 8 mg/kg regimen instead of the fixed dose 600 mg tocilizumab regimen. Similarly,
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