Introduction Early literature on the COVID-19 pandemic indicated striking ethnic inequalities in SARS-CoV-2-related outcomes. This systematic review and meta-analysis aimed to describe the presence... Show moreIntroduction Early literature on the COVID-19 pandemic indicated striking ethnic inequalities in SARS-CoV-2-related outcomes. This systematic review and meta-analysis aimed to describe the presence and magnitude of associations between ethnic groups and COVID-19-related outcomes. Methods PubMed and Embase were searched from December 2019 through September 2020. Studies reporting extractable data (ie, crude numbers, and unadjusted or adjusted risk/ORs) by ethnic group on any of the five studied outcomes: confirmed COVID-19 infection in the general population, hospitalisation among infected patients, and disease severity, intensive care unit (ICU) admission and mortality among hospitalised patients with SARS-CoV-2 infection, were included using standardised electronic data extraction forms. We pooled data from published studies using random-effects meta-analysis. Results 58 studies were included from seven countries in four continents, mostly retrospective cohort studies, covering a total of almost 10 million individuals from the first wave until the summer of 2020. The risk of diagnosed SARS-CoV-2 infection was higher in most ethnic minority groups than their White counterparts in North American and Europe with the differences remaining in the US ethnic minorities after adjustment for confounders and explanatory factors. Among people with confirmed infection, African-Americans and Hispanic-Americans were also more likely than White-Americans to be hospitalised with SARS-CoV-2 infection. No increased risk of COVID-19 outcomes (ie, severe disease, ICU admission and death) was found among ethnic minority patients once hospitalised, except for a higher risk of death among ethnic minorities in Brazil. Conclusion The risk of SARS-CoV-2 diagnosis was higher in most ethnic minorities, but once hospitalised, no clear inequalities exist in COVID-19 outcomes except for the high risk of death in ethnic minorities in Brazil. The findings highlight the necessity to tackle disparities in social determinants of health, preventative opportunities and delay in healthcare use. Ethnic minorities should specifically be considered in policies mitigating negative impacts of the pandemic. PROSPERO registration number CRD42020180085. Show less
Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all... Show morePurpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when con -sidering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients. ? 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Objective We aimed to describe the associations of age and sex with the risk of COVID-19 in different severity stages ranging from infection to death. Design Systematic review and meta-analysis.... Show moreObjective We aimed to describe the associations of age and sex with the risk of COVID-19 in different severity stages ranging from infection to death. Design Systematic review and meta-analysis. Data sources PubMed and Embase through 4 May 2020. Study selection We considered cohort and case-control studies that evaluated differences in age and sex on the risk of COVID-19 infection, disease severity, intensive care unit (ICU) admission and death. Data extraction and synthesis We screened and included studies using standardised electronic data extraction forms and we pooled data from published studies and data acquired by contacting authors using random effects meta-analysis. We assessed the risk of bias using the Newcastle-Ottawa Scale. Results We screened 11.550 titles and included 59 studies comprising 36.470 patients in the analyses. The methodological quality of the included papers was high (8.2 out of 9). Men had a higher risk for infection with COVID-19 than women (relative risk (RR) 1.08, 95% CI 1.03 to 1.12). When infected, they also had a higher risk for severe COVID-19 disease (RR 1.18, 95% CI 1.10 to 1.27), a higher need for intensive care (RR 1.38, 95% CI 1.09 to 1.74) and a higher risk of death (RR 1.50, 95% CI 1.18 to 1.91). The analyses also showed that patients aged 70 years and above have a higher infection risk (RR 1.65, 95% CI 1.50 to 1.81), a higher risk for severe COVID-19 disease (RR 2.05, 95% CI 1.27 to 3.32), a higher need for intensive care (RR 2.70, 95% CI 1.59 to 4.60) and a higher risk of death once infected (RR 3.61, 95% CI 2.70 to 4.84) compared with patients younger than 70 years. Conclusions Meta-analyses on 59 studies comprising 36.470 patients showed that men and patients aged 70 and above have a higher risk for COVID-19 infection, severe disease, ICU admission and death. PROSPERO registration number CRD42020180085. Show less
Kwesi-Maliepaard, E.M.; Aslam, M.A.; Alemdehy, M.F.; Brand, T. van den; McLean, C.; Vlaming, H.; ... ; Jacobs, H. 2020
Cytotoxic T cell differentiation is guided by epigenome adaptations, but how epigenetic mechanisms control lymphocyte development has not been well defined. Here we show that the histone... Show moreCytotoxic T cell differentiation is guided by epigenome adaptations, but how epigenetic mechanisms control lymphocyte development has not been well defined. Here we show that the histone methyltransferase DOT1L, which marks the nucleosome core on active genes, safeguards normal differentiation of CD8(+) T cells. T cell-specific ablation of DOT1L resulted in loss of naive CD8(+) T cells and premature differentiation toward a memory-like state, independent of antigen exposure and in a cell-intrinsic manner. Mechanistically, DOT1L controlled CD8(+) T cell differentiation by ensuring normal T cell receptor density and signaling. DOT1L also maintained epigenetic identity, in part by indirectly supporting the repression of developmentally regulated genes. Finally, deletion of DOT1L in T cells resulted in an impaired immune response. Through our study, DOT1L is emerging as a central player in physiology of CD8(+) T cells, acting as a barrier to prevent premature differentiation and controlling epigenetic integrity. Show less
Wall, S. van der; Hendriks, S.; Huisman, M.; Klok, F.A. 2018
