Introduction Since the first reports of COVID-19 cases, sex-discrepancies have been reported in COVID-19 mortality. We provide a detailed description of these sex differences in relation to age and comorbidities among notified cases as well as in relation to age and sex-specific mortality in the general Dutch population. Methods Data on COVID-19 cases and mortality until May 31st 2020 was extracted from the national surveillance database with exclusion of healthcare workers. Association between sex and case fatality was analyzed with multivariable logistic regression. Subsequently, male–female ratio in standardized mortality ratios and population mortality rates relative to all-cause and infectious disease-specific mortality were computed stratified by age. Results Male–female odds ratio for case fatality was 1.33 [95% CI 1.26–1.41] and among hospitalized cases 1.27 [95% CI 1.16–1.40]. This remained significant after adjustment for age and comorbidities. The male–female ratio of the standardized mortality ratio was 1.70 [95%CI 1.62–1.78]. The population mortality rate for COVID-19 was 35.1 per 100.000, with a male–female rate ratio of 1.25 (95% CI 1.18–1.31) which was higher than in all-cause population mortality and infectious disease mortality. Conclusion Our study confirms male sex is a predisposing factor for severe outcomes of COVID-19, independent of age and comorbidities. In addition to general male–female-differences, COVID-19 specific mechanisms likely contribute to this mortality discrepancy.

Introduction: Current guidelines advocate empirical antibiotic treatment (EAT) in haematological patients with febrile neutropenia. However, the optimal duration of EAT is unknown. In 2011, we have introduced a protocol, promoting discontinuation of carbapenems as EAT after three days in most patients and discouraging the standard use of vancomycin as EAT.[NF1] This study assesses the effect of this protocol on carbapenem and vancomycine use in high risk haematological patients and its safety.Methods: A retrospective before-after study was performed comparing a cohort from 2007 to 2011 (period I, before restrictive EAT use) with a cohort from 2011-2014 (period II, restrictive EAT use). Neutropenic episodes related to chemotherapy or stem cell transplantation (SCT) in patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) were analysed. The primary outcome was the use of carbapenems and vancomycin as EAT during neutropenia, expressed as days of therapy (DOT)/100 neutropenic days and analysed with interrupted time series (ITS). Also the use of other antibiotics was analysed to evaluate the overall antibiotic use[NF2] . Safety measurements included 30-day mortality, ICU admittance within 30 days after start of EAT and blood cultures positive for microorganisms sensitive to a carbapenem.Results: 362 neutropenic episodes with a median duration of 18 days were analysed, involving 201 patients. ITS analysis showed decreased carbapenem use with a step change of 16.1 DOT/100 neutropenic days (CI -26.73 to -1.41) and an overall reduction of 21.6% (8.7 DOT/100 neutropenic days). [NF3] Vancomycin use decreased with a step change of 13.7 DOT/100 neutropenic days (95% CI -23.66 to -2.90) and an overall reduction of 54.7% (14.6 DOT/100 neutropenic days). [NF4] There were no striking differences in other therapeutically used broad-spectrum antibiotics. No deaths were directly related to early discontinuation of EAT, also no notable difference in ICU-admission (n=9 in period I, n=9 in period II) and positive blood cultures (n=4 in period I, n=2 in period II) [NF5] was detected.Conclusion: The introduction of a protocol promoting restrictive use of EAT resulted in reduction of carbapenem and vancomycin use and appears to be safe in AML or high-risk MDS patients with febrile neutropenia during chemotherapy or SCT.

Introduction: Since the first reports of COVID-19 cases, sex-discrepancies have been reported in COVID-19 mortality. We provide a detailed description of these sex differences in relation to age and comorbidities among notified cases as well as in relation to age and sex specific mortality in the general Dutch population. Methods: Data on COVID-19 cases and mortality until May 31st was extracted from the national surveillance database with exclusion of healthcare workers. Association between sex and case fatality was analyzed with multivariable logistic regression. Subsequently, male-female ratio in standardized mortality ratios and population mortality rates relative to all-cause and infectious diseases-specific mortality were computed stratified by age.Results: Male-female odds ratio for case fatality was 1.33 [95% CI 1.26-1.41] and among hospitalized cases 1.27 [95% CI 1.16-1.40]. This remained significant after adjustment for age and comorbidities. The male-female ratio of the standardized mortality ratio was 1.70 [95%CI 1.62-1.78]. The population mortality rate was 35.1 per 100.000, with a male-female rate ratio of 1.25 (95% CI 1.18-1.31) which was higher than in all-cause and infectious disease mortality.Conclusion: Our study confirms male sex is a predisposing factor for severe outcomes of COVID-19, independent of age and comorbidities. The underlying mechanisms are likely to be COVID-19 specific.

Introduction: Current guidelines advocate empirical antibiotic treatment (EAT) in haematological patients with febrile neutropenia. However, the optimal duration of EAT is unknown. In 2011, we have implemented a protocol advocating more restrictive use of EAT in patients with febrile neutropenia. This study assesses the effect of this protocol on carbapenem use in high risk haematological patients and its safety. Methods: A retrospective before-after study was performed comparing a cohort from 2007 to 2011 (period I, before restrictive EAT use) with a cohort from 2011-2014 (period II, restrictive EAT use). Neutropenic episodes related to chemotherapy or stem cell transplantation (SCT) in patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) were analysed. The primary outcome was the use of carbapenems as EAT during neutropenia, expressed as days on therapy (DOT). Also the use of other antibiotics was analysed. Safety measurements included 30-day mortality, ICU admittance within 30 days after start of EAT and blood cultures positive for microorganisms sensitive to a carbapenem. Results: 362 neutropenic episodes with a median duration of 18 days were analysed, involving 201 patients. DOT with carbapenems decreased from a median of eight days (period I) to a median of six days (period II), a reduction of 25%. Additionally, vancomycin use decreased with 55%. No deaths were directly related to early discontinuation of EAT, also no notable difference in ICU-admission and positive blood cultures was detected. Conclusion: Implementation of a protocol promoting restrictive use of EAT resulted in reduction of carbapemen use and appears to be safe in AML or high-risk MDS patients with febrile neutropenia during chemotherapy or SCT.