No abstract

Background Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown. Methods In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58–77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis. Results In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02–5.45], OR0.68[0.59–0.79], respectively;both p<  0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55–0.75], DM OR1.47[1.26–1.72], CKD OR1.61[1.32–1.97], COPD OR1.30[1.07–1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome. Conclusions Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities. Trial registration CAPACITY-COVID (NCT04325412)

Aims Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. Methods and results We used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existing heart disease and in-hospital mortality. A total of 16 511 patients with COVID-19 were included (21.1% aged 66–75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male, and often had other comorbid conditions when compared with those without. Mortality was higher in patients with cardiac disease (29.7%; n = 1545 vs. 15.9%; n = 1797). However, following multivariable adjustment, this difference was not significant [adjusted risk ratio (aRR) 1.08, 95% confidence interval (CI) 1.02–1.15; P = 0.12 (corrected for multiple testing)]. Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure (aRR 1.19, 95% CI 1.10–1.30; P &lt; 0.018) particularly for severe (New York Heart Association class III/IV) heart failure (aRR 1.41, 95% CI 1.20–1.64; P &lt; 0.018). None of the other heart disease subtypes, including ischaemic heart disease, remained significant after multivariable adjustment. Serious cardiac complications were diagnosed in &lt;1% of patients. Conclusion Considerable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare during hospitalization.

A qualitative GC/MS profile was obtained and its mass spectrometric features characterized for the analysis of the enantiomers of (RS)‐3,4‐methylenedioxymethamphetamine (MDMA) and its metabolites (RS)‐3,4‐methylenedioxyamphetamine (MDA), (RS)‐4‐hydroxy‐3‐methoxymethamphetamine (HMMA) and (RS)‐4‐hydroxy‐3‐methoxyamphetamine (HMA). A chiral derivatization method was selected to obtain the diastereomers required for the separation of the respective enantiomers with a non‐chiral GC stationary phase. The selected derivatization consisted of a reaction with N‐heptafluorobutyryl‐(S)‐prolyl chloride combined with a consecutive reaction with N‐methyl‐N‐trimethylsilyltrifluoroacetamide, resulting in N‐[heptafluorobutyryl‐(S)‐prolyl]‐O‐trimethylsilyl derivatives. Detection was carried out with electron ionization and positive chemical ionization (PCI) ion trap mass spectrometry. Mass spectra of the derivatives of reference standards of the compounds of interest obtained with PCI demonstrated that this method simultaneously induces proton and charge‐transfer reactions in the ion trap. The advantage is that high mass information is provided while some fragmentation remains to elucidate structural details. Subsequently, in three urine samples obtained from different and unrelated MDMA intoxications, the enantiomers of MDMA and MDA were identified. In some urine samples also HMMA and/or HMA were found. In addition to these compounds, an unexpected compound and/or additional chiral metabolite, N‐hydroxy‐(RS)‐3,4‐methylenedioxyamphetamine, was identified in two out of three urine samples. Preliminary results also indicated an enantioselective metabolism in the N‐demethylation pathway for MDMA in humans. © 1997 John Wiley & Sons, Ltd.