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1.
J Hypertens ; 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1550601

ABSTRACT

BACKGROUND: The severity of COVID-19 after SARS-CoV-2 infection is unpredictable. Angiotensin-converting enzyme-2 (ACE2) is the receptor responsible for coronavirus binding, while subsequent cell entry relies on priming by the serine protease TMPRSS2 (transmembrane protease, serine 2). Although renin-angiotensin-aldosterone-system (RAAS) blockers have been suggested to upregulate ACE2, their use in COVID-19 patients is now considered well tolerated. The aim of our study was to investigate parameters that determine COVID-19 severity, focusing on RAAS-components and variation in the genes encoding for ACE2 and TMPRSS2. METHODS: Adult patients hospitalized due to SARS-CoV-2 infection between May 2020 and October 2020 in the Haga Teaching Hospital were included, and soluble ACE2 (sACE2), renin, aldosterone (in heparin plasma) and polymorphisms in the ACE2 and TMPRSS2 genes (in DNA obtained from EDTA blood) were determined. MEASUREMENTS AND MAIN RESULTS: Out of the 188 patients who were included, 60 were defined as severe COVID-19 (ICU and/or death). These patients more often used antidiabetic drugs, were older, had higher renin and sACE2 levels, lower aldosterone levels and a lower aldosterone/renin ratio. In addition, they displayed the TMPRSS2-rs2070788 AA genotype less frequently. No ACE2 polymorphism-related differences were observed. Multivariate regression analysis revealed independent significance for age, sACE2, the aldosterone/renin ratio, and the TMPRSS2 rs2070788 non-AA genotype as predictors of COVID-19 severity, together yielding a C-index of 0.79. Findings were independent of the use of RAAS blockers. CONCLUSION: High sACE2, a low aldosterone/renin ratio and having the TMPRSS2 rs2070788 non-AA genotype are novel independent determinants that may help to predict COVID-19 disease severity. TRIAL REGISTRATION: retrospectively registered.

2.
Clin Infect Dis ; 2021 Nov 16.
Article in English | MEDLINE | ID: covidwho-1522156

ABSTRACT

BACKGROUND: We aimed to determine the non-inferiority of fosfomycin, compared to ciprofloxacin, as oral stepdown treatment for E. coli febrile urinary tract infections (fUTIs) in women. METHODS: This was a double-blind, randomised controlled trial in 15 Dutch hospitals. Adult women receiving 2-5 days of empirical intravenous antimicrobials for E.coli fUTI, were assigned to stepdown treatment with once-daily 3 gr fosfomycin or twice-daily 0.5 gr ciprofloxacin, for 10 days of total antibiotic treatment. For the primary endpoint clinical cure at day 6-10 post-end-of-treatment a non-inferiority margin of 10% was chosen. The trial was registered on Trialregister.nl (NTR6449). RESULTS: After enrolment of 97 patients between 2017-2020, the trial ended prematurely because of the Covid-19 pandemic. The primary endpoint was met in 36/48 patients (75.0%) assigned to fosfomycin and 30/46 patients (65.2%) assigned to ciprofloxacin (Risk Difference: 9.6%, 95%-Confidence-Interval: -8.8% to 28.0%). In patients assigned to fosfomycin and ciprofloxacin, microbiological cure at day 6-10 post-end-of-treatment occurred in 29/37 (78.4%) and 33/35 (94.3%; RD: -16.2%, 95%CI: -32.7 to -0.0%), and clinical cure at day 30-35 post-end-of-treatment occurred in 35/47 (75.6%) and 33/44 (75.0%; RD: 0.4%, 95%CI: -18·4% to 17·6%) respectively. Any adverse event was reported in 35/48 (72.9%) and 32/46 (69.6%) patients (RD: 3.3%, 95%CI: -15.0% to 21.6%%), and any gastro-intestinal adverse event in 25/48 (52.1%) and 14/46 (30.4%) patients (RD: 20.8%, 95%CI: 1.6% to 40.0%), respectively. CONCLUSIONS: Fosfomycin is non-inferior to ciprofloxacin as oral stepdown treatment for fUTI caused by E.coli in women. Fosfomycin use is associated with more gastro-intestinal events.

3.
J Clin Med ; 10(19)2021 Sep 30.
Article in English | MEDLINE | ID: covidwho-1463722

ABSTRACT

BACKGROUND: The Netherlands strives for hepatitis C virus (HCV) elimination, in accordance with the World Health Organization targets. An accurate estimate when HCV elimination will be reached is elusive. We have embarked on a nationwide HCV elimination project (CELINE) that allowed us to harvest detailed data on the Dutch HCV epidemic. This study aims to provide a well-supported timeline towards HCV elimination in The Netherlands. METHODS: A previously published Markov model was used, adopting published data and unpublished CELINE project data. Two main scenarios were devised. In the Status Quo scenario, 2020 diagnosis and treatment levels remained constant in subsequent years. In the Gradual Decline scenario, an annual decrease of 10% in both diagnoses and treatments was implemented, starting in 2020. WHO incidence target was disregarded, due to low HCV incidence in The Netherlands (≤5 per 100,000). RESULTS: Following the Status Quo and Gradual Decline scenarios, The Netherlands would meet WHO's elimination targets by 2027 and 2032, respectively. From 2015 to 2030, liver-related mortality would be reduced by 97% in the Status Quo and 93% in the Gradual Decline scenario. Compared to the Status Quo scenario, the Gradual Decline scenario would result in 12 excess cases of decompensated cirrhosis, 18 excess cases of hepatocellular carcinoma, and 20 excess cases of liver-related death from 2020-2030. CONCLUSIONS: The Netherlands is on track to reach HCV elimination by 2030. However, it is vital that HCV elimination remains high on the agenda to ensure adequate numbers of patients are being diagnosed and treated.

4.
Emerg Med J ; 38(9): 685-691, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1320447

ABSTRACT

BACKGROUND: Guidelines recommend maximal efforts to obtain blood and sputum cultures in patients with COVID-19, as bacterial coinfection is associated with worse outcomes. The aim of this study was to evaluate the yield of bacteriological tests, including blood and sputum cultures, and the association of multiple biomarkers and the Pneumonia Severity Index (PSI) with clinical and microbiological outcomes in patients with COVID-19 presenting to the emergency department (ED). METHODS: This is a substudy of a large observational cohort study (PredictED study). The PredictED included adult patients from whom a blood culture was drawn at the ED of Haga Teaching Hospital, The Netherlands. For this substudy, all patients who tested positive for SARS-CoV-2 by PCR in March and April 2020 were included. The primary outcome was the incidence of bacterial coinfection. We used logistic regression analysis for associations of procalcitonin, C reactive protein (CRP), ferritin, lymphocyte count and PSI score with a severe disease course, defined as intensive care unit admission and/or 30-day mortality. The area under the receiver operating characteristics curve (AUC) quantified the discriminatory performance. RESULTS: We included 142 SARS-CoV-2 positive patients. On presentation, the median duration of symptoms was 8 days. 41 (29%) patients had a severe disease course and 24 (17%) died within 30 days. The incidence of bacterial coinfection was 2/142 (1.4%). None of the blood cultures showed pathogen growth while 6.3% was contaminated. The AUCs for predicting severe disease were 0.76 (95% CI 0.68 to 0.84), 0.70 (0.61 to 0.79), 0.62 (0.51 to 0.74), 0.62 (0.51 to 0.72) and 0.72 (0.63 to 0.81) for procalcitonin, CRP, ferritin, lymphocyte count and PSI score, respectively. CONCLUSION: Blood cultures appear to have limited value while procalcitonin and the PSI appear to be promising tools in helping physicians identify patients at risk for severe disease course in COVID-19 at presentation to the ED.


Subject(s)
Bacterial Infections/diagnosis , Bacteriological Techniques/methods , COVID-19/diagnosis , Coinfection/diagnosis , Adult , Aged , Aged, 80 and over , Bacterial Infections/blood , Bacterial Infections/complications , Bacterial Infections/microbiology , Bacteriological Techniques/statistics & numerical data , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , COVID-19/virology , COVID-19 Nucleic Acid Testing , Coinfection/blood , Coinfection/epidemiology , Coinfection/microbiology , Emergency Service, Hospital , Female , Ferritins/blood , Humans , Incidence , Lymphocyte Count , Male , Middle Aged , Netherlands/epidemiology , Procalcitonin/blood , Prognosis , ROC Curve , Retrospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Severity of Illness Index
5.
Clin Infect Dis ; 72(7): 1256-1258, 2021 04 08.
Article in English | MEDLINE | ID: covidwho-1174888

ABSTRACT

We report a case of a man with COVID-19 who developed acute hepatotoxicity related to remdesivir with probable interaction of P-glycoprotein (P-gp) inhibitors. Until further details on this interaction become available, we recommend physicians to be cautious with the prescription of P-gp inhibitors in patients receiving remdesivir therapy.


Subject(s)
COVID-19 , Chemical and Drug Induced Liver Injury , ATP Binding Cassette Transporter, Subfamily B , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/adverse effects , COVID-19/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Humans , Male , SARS-CoV-2
6.
BMJ Open ; 11(2): e039085, 2021 02 09.
Article in English | MEDLINE | ID: covidwho-1075972

ABSTRACT

INTRODUCTION: Antimicrobial treatment of asymptomatic bacteriuria (ASB) is one of the most common unnecessary uses of antimicrobials. Earlier studies have shown that the prevalence of this inappropriate treatment ranges from 45% to 83%. Multifaceted interventions based on international guidelines and antimicrobial stewardship can decrease overtreatment of ASB. We have designed a study protocol with the main objective of reducing overtreatment of ASB by 50% through use of a deimplementation strategy. METHODS AND ANALYSIS: We will use a stepped-wedge cluster randomised design, comparing outcomes before and after introduction of our intervention in the emergency department (ED) of five hospitals (clusters) in the Netherlands. All patients (≥18 years old) who have a urine test performed in the ED will be screened for eligibility. The deimplementation strategy consists of a combination of interventions, including education, audit and feedback. The primary endpoint is overtreatment of ASB in patients without risk factors (eg, pregnancy, planned invasive urological procedures and neutropenia). Secondary endpoints are the duration of antimicrobial treatment for ASB, the number of urine cultures and urinalysis per 1000 patients, and overtreatment of positive urinalysis in asymptomatic patients. ETHICS AND DISSEMINATION: Ethical approval was obtained from the medical ethics research committee of the Academic Medical Centre (Amsterdam, the Netherlands) with a waiver for informed consent. Local feasibility was obtained by the local institutional review boards of all participating hospitals. Our study aims to reduce inappropriate screening and treatment of ASB in EDs, improve healthcare quality, lower the increase in antimicrobial resistance and save costs. If proven (cost)-effective, this study provides a well-suited strategy for a nationwide approach to reduce overtreatment of ASB. Relevant results of our study will be disseminated through publications in peer-reviewed journals and presentations at relevant (scientific) conferences. TRIAL REGISTRATION NUMBER: NL8242; Pre-results.


Subject(s)
Antimicrobial Stewardship , Bacteriuria , Adolescent , Anti-Bacterial Agents/therapeutic use , Bacteriuria/diagnosis , Bacteriuria/drug therapy , Humans , Medical Overuse , Netherlands , Randomized Controlled Trials as Topic
7.
Age Ageing ; 50(3): 631-640, 2021 05 05.
Article in English | MEDLINE | ID: covidwho-1054261

ABSTRACT

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. OBJECTIVE: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. METHODS: This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. RESULTS: A total of 1,376 patients were included (median age 78 years (interquartile range 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3-3.0)) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8-4.3)). CONCLUSIONS: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.


Subject(s)
COVID-19/mortality , Frail Elderly/statistics & numerical data , Frailty/complications , Hospitalization/statistics & numerical data , Pandemics/statistics & numerical data , Aged , Aged, 80 and over , Female , Frailty/diagnosis , Hospital Mortality , Humans , Male , Netherlands/epidemiology , Retrospective Studies , SARS-CoV-2
8.
Clin Infect Dis ; 72(7): 1256-1258, 2021 04 08.
Article in English | MEDLINE | ID: covidwho-619915

ABSTRACT

We report a case of a man with COVID-19 who developed acute hepatotoxicity related to remdesivir with probable interaction of P-glycoprotein (P-gp) inhibitors. Until further details on this interaction become available, we recommend physicians to be cautious with the prescription of P-gp inhibitors in patients receiving remdesivir therapy.


Subject(s)
COVID-19 , Chemical and Drug Induced Liver Injury , ATP Binding Cassette Transporter, Subfamily B , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/adverse effects , COVID-19/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Humans , Male , SARS-CoV-2
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