Ann Epidemiol

PURPOSE: Prognostic studies derived from samples of patients managed in tertiary hospitals are subject to referral bias. We aimed to characterise this bias using the example of infective endocarditis (IE). METHODS: We analysed data from a French population-based cohort which included 497 patients with IE in 2008. Patients were admitted directly to a tertiary hospital (group T), or admitted to a non-tertiary hospital and referred to a tertiary hospital (group NTT) or not (group NT). We compared patients' characteristics and survival rates and prognostic factors between groups. RESULTS: Compared to group T (N=291), NTT patients (N=144) were more often males (81.3% vs 72.5%, p=0.046), injection drug users (9.7% vs 4.5%, p=0.033), had more frequent surgical indications (78.5% vs 64.3%, p=0.003). Compared to group NT (N=62), NTT patients were more often males (81.3% vs 67.7%, p=0.034) and had surgical indications more often (78.5% vs 19.4%, p<0.001). One-year survival was higher in (NTT+T) patients than in NT patients (73.0% vs 56.1%, p=0.01). Prognostic factors as well as HR estimates varied across groups. CONCLUSION: When derived from samples mixing patients admitted directly and those referred to tertiary hospitals, validity of characteristics description, survival estimates, and HRs is threatened by referral bias

Data Brief

This article describes supplementary tables and figures associated with the research paper entitled "Impact of referral bias on prognostic studies outcomes: insights from a population-based cohort study on infective endocarditis". The aforementioned paper is a secondary analysis of data from the EI 2008 cohort on infective endocarditis and aimed at characterising referral bias. A total of 497 patients diagnosed with definite infective endocarditis between January 1(st) and December 31(st) 2008 were included in EI 2008. Data were collected from hospital medical records by trained clinical research assistants. Patients were divided into three groups: admitted to a tertiary hospital (group T), admitted to a non-tertiary hospital and referred secondarily to a tertiary hospital (group NTT) or admitted to a non-tertiary hospital and not referred (group NT). The pooled (NTT+T) group mimicked studies recruiting patients in tertiary hospitals only. Two different starting points were considered for follow up: date of first hospital admission and date of first admission to a tertiary hospital if any (hereinafter referred to as "referral time"). Referral bias is a type of selection bias which can occur due to recruitment of patients in tertiary hospitals only (excluding those who are admitted to non-tertiary hospitals and not referred to tertiary hospitals). This bias may impact the description of patients' characteristics, survival estimates as well as prognostic factors identification. The six tables presented in this paper illustrate how patients' selection (population-based sample [pooled (NT+NTT+T) group] versus recruitment in tertiary hospitals only [pooled (NTT+T) group]) might impact Hazards Ratios values for prognostic factors. Crude and adjusted Cox regression analyses were first performed to identify prognostic factors associated with 3-month and 1-year mortality in the whole sample using inclusion as the starting point. Analyses were then performed in the pooled (NTT+T) group first using inclusion as the starting point and finally using referral time as the starting point. Figures 1 to 3 illustrate how HR increase with time for covariates that were considered as time-varying covariates (covariate*time interaction)

Clin Infect Dis

BACKGROUND: The 2023 Duke-ISCVID Criteria for infective endocarditis (IE) were proposed as an updated diagnostic classification of IE. Using an open prospective multicenter cohort of patients treated for IE, we compared the performance of these new criteria to that of the 2000 Modified Duke and 2015 ESC criteria. METHODS: Cases of patients treated for IE between January 2017 and October 2022 were adjudicated as certain IE or not. Each case was also categorized as either definite or possible/rejected within each classification. Sensitivity, specificity, and accuracy were estimated, with 95% confidence intervals. RESULTS: Of the 1194 patients analyzed (mean age 66.1 years, 71.2% men), 414 (34.7%) had a prosthetic valve and 284 (23.8%) had a cardiac implanted electronic device (CIED); 946 (79.2%) were adjudicated as certain IE; 978 (81.9%), 997 (83.5%), and 1057 (88.5%) were classified as definite IE in the 2000 modified Duke, 2015 ESC, and 2023 Duke-ISCVID criteria, respectively. The sensitivity of each set of criteria was 93.2% [91.6-94.8], 95.0% [93.7-96.4], and 97.6% [96.6-98.6], respectively (p<.001 for all 2-by-2 comparisons). Corresponding specificity rates were 61.3% [55.2-67.4), 60.5% [54.4-66.6], and 46.0% [39.8-52.2], respectively. In patients without CIED, sensitivity rates were 94.8% [93.2-96.4], 96.5% [95.1-97.8], and 97.7% [96.6-98.8] and specificity rates were 59.0% [51.6-66.3], 56.6% [49.3-64.0], and 53.8% [46.3-61.2], respectively. CONCLUSION: Overall, the 2023 Duke-ISCVID criteria had a significantly higher sensitivity but a significantly lower specificity, compared to older criteria. This decreased specificity was mainly attributable to patients with CIED

Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

International audienceFor the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences

Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): A phase 3, randomized, double-blind, placebo-controlled trial

International audienc

Oropharyngeal and intestinal concentrations of opportunistic pathogens are independently associated with death of SARS-CoV-2 critically ill adults

International audienceBackground The composition of the digestive microbiota may be associated with outcome and infections in patients admitted to the intensive care unit (ICU). The dominance by opportunistic pathogens (such as Enterococcus ) has been associated with death. However, whether this association remains all throughout the hospitalization are lacking. Methods We performed a single-center observational prospective cohort study in critically ill patients admitted with severe SARS-CoV-2 infection. Oropharyngeal and rectal swabs were collected at admission and then twice weekly until discharge or death. Quantitative cultures for opportunistic pathogens were performed on oropharyngeal and rectal swabs. The composition of the intestinal microbiota was assessed by 16S rDNA sequencing. Oropharyngeal and intestinal concentrations of opportunistic pathogens, intestinal richness and diversity were entered into a multivariable Cox model as time-dependent covariates. The primary outcome was death at day 90. Results From March to September 2020, 95 patients (765 samples) were included. The Simplified Acute Physiology Score 2 ( SAPS 2) at admission was 33 [24; 50] and a Sequential Organ Failure Assessment score (SOFA score) at 6 [4; 8]. Day 90 all-cause mortality was 44.2% (42/95). We observed that the oropharyngeal and rectal concentrations of Enterococcus spp., Staphylococcus aureus and Candida spp. were associated with a higher risk of death. This association remained significant after adjustment for prognostic covariates (age, chronic disease, daily antimicrobial agent use and daily SOFA score). A one-log increase in Enterococcus spp . , S. aureus and Candida spp. in oropharyngeal or rectal swabs was associated with a 17% or greater increase in the risk of death. Conclusion We found that elevated oropharyngeal/intestinal Enterococcus spp. S. aureus and Candida spp. concentrations, assessed by culture, are associated with mortality, independent of age, organ failure, and antibiotic therapy, opening prospects for simple and inexpensive microbiota-based markers for the prognosis of critically ill SARS-CoV-2 patients

Cardiac Adverse Events and Remdesivir in Hospitalized Patients with Coronavirus Disease 2019 (COVID-19): A Post Hoc Safety Analysis of the Randomized DisCoVeRy Trial

International audienceBackground We aimed to evaluate the cardiac adverse events (AEs) in hospitalized patients with Coronavirus Disease 2019 (COVID-19) receiving remdesivir plus standard of care (SoC) compared to SoC alone (control), as an association was noted in some cohort studies and disproportionality analyses of safety databases. Methods This post-hoc safety analysis is based on data from the multicenter, randomized, open-label, controlled DisCoVeRy trial in hospitalized patients with COVID-19 (NCT04315948). Any first AE occurring between randomization and day 29 in the modified intention-to-treat (mITT) population randomized to either remdesivir or control group was considered. Analysis was performed using Kaplan-Meier survival curves and Kaplan-Meier estimates were calculated for event rates. Results Cardiac AEs were reported in 46 (11.2%) of 410 and 48 (11.3%) of 423 patients in the mITT population (n = 833) enrolled in the remdesivir and control groups, respectively. The difference between both groups was not significant (HR 1.0, 95% CI 0.7-1.5, p = 0.98), even when evaluating serious and non-serious cardiac AEs separately. The majority of reports in both groups were of arrhythmic nature (remdesivir, 84.8%; control, 83.3%) and were associated with a favorable outcome. There was no significant difference between remdesivir and control groups in the occurrence of different cardiac AE subclasses, including arrhythmic events (HR 1.1, 95% CI: 0.7-1.7, p = 0.68). Conclusions Remdesivir treatment was not associated with an increased risk of cardiac AEs, whether serious or not, and regardless of AE severity, compared to control, in patients hospitalized with moderate or severe COVID-19. This is consistent with the results of other randomized controlled trials and meta-analyses

Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial

International audienc

Final results of the DisCoVeRy trial of remdesivir for patients admitted to hospital with COVID-19

International audienc