206 Chapter 9 comparing the 8 mg/kg regimen with the 400 mg tocilizumab gave a NNT of 39, and comparing it to 400 mg sarilumab gave an NNT of 20. In the second scenario, even though 1.5 to twice as many patients could be treated with 400 mg fixed dose tocilizumab, more lives would be saved by using the 8 mg/kg. However, there are many other considerations, like equal distribution of medication. The odds of reaching the combined (secondary) outcome of ICU admission or mortality were also higher for 600 mg fixed dose tocilizumab, 400 mg fixed dose tocilizumab and 400 mg sarilumab compared to 8 mg/kg tocilizumab. Both hospital length of stay and ICU length of stay were longer in the 8 mg/kg group than other treatment regimens. An important limitation is the potential of time-associated residual confounding, as patient characteristics like age, sex and social economic status could influence the time at which an individual is infected with SARS-CoV-2, and thus the IL-6 treatment regimen. While it was possible to correct for some of these variables, data for some potential confounders were not available. Based on these results, 8 mg/kg tocilizumab led to improved survival compared to 600 mg fixed dose tocilizumab, 400 mg fixed dose tocilizumab and 400 mg sarilumab, and 8 mg/kg would therefore be the first-choice option. In the case of ongoing drug-shortages, using a lower dose to treat more patients could be considered, or defining criteria based on which patients could be selected who are expected to benefit most from treatment. In Chapter 6 the duration of mechanical ventilation, the P/F ratio and in-hospital mortality were compared between patients who underwent elective cardiac surgery during a season with high prevalence of Influenza-Like Illness (ILI season) and a season with low incidence of ILI (baseline season). Earlier studies found a higher prevalence of ARDS and a longer duration of IMV in patients who underwent elective cardiac surgery in ILI season compared to baseline season38. The hypothesis was that an asymptomatic or presymptomatic respiratory viral infection was a risk factor for (pulmonary) complications after cardiac surgery. For this study, the NICE database was used, which includes ICU data from all 16 hospitals in the Netherlands that perform cardiac surgery39. A total of 42.277 adult patients who underwent elective cardiac surgery were included: 30.7% underwent surgery in ILI season, 31.8% in baseline season and 37.5% in the intermediate season. The primary outcome measure was time to extubation, and the hazard for extubation was compared between ILI season and baseline season. Because the severity of the ILI season changes per year, an interaction term between the year in which surgery was performed and the season in which surgery was performed was included. This way, the hazard ratio could be calculated for each ILI season, compared with the baseline season in the same year. After correcting for confounding variables, the time to extubation was slightly shorter in ILI season compared to baseline season for the 2014-2015 season (HR 1.15, 95% CI 1.04-1.26), the 2015-2016 season (HR 1.22, 95% CI 1.12-1.33) and the 20172018 season (HR 1.25; 95% CI, 1.16-1.36). Time to extubation was not significantly
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