Impact of the COVID-19 pandemic on lung cancer diagnoses and mortality: A nationwide study in France.

BACKGROUND: During the first wave of the COVID-19 pandemic, a reduction in the number of newly diagnosed cases of lung cancer has been reported worldwide, often associated with a higher proportion of cases diagnosed at an advanced stage compared with previous years. METHODS: Using the French National Hospital Database, we investigated incident lung cancer cases and their mortality during pandemic years 2020 and 2021, compared to predictions based on pre-pandemic years 2013-2019. Mortality was assessed up to 24 months following incidence date. Expected numbers of incident cases and all-cause deaths during the pandemic were estimated using Poisson regression models and survival was analyzed using Cox regressions. RESULTS: The database included 397,092 incident lung cancer cases in total, 20 % of whom underwent thoracic surgery. During the first pandemic wave (March-June 2020), there were 12 % i.e., 1940 fewer incident lung cancer cases than the expected figure (16,325), while no significant difference was found thereafter. Survival at 6 and 24 months improved steadily from 2013 to 2019 and continued to improve during pandemic years 2020-2021. However, during the first wave, a slight excess mortality was observed compared with predictions based on pre-pandemic trends. CONCLUSIONS: The lower incidence observed during the first wave with no catch-up in the following periods could be explained by deaths among yet undiagnosed patients, either from COVID-19 or as a result of barriers to accessing healthcare. The excess mortality observed for both operated and non-operated patients may be attributable to delayed diagnosis, as well as to COVID-19-related deaths.

Human metapneumovirus infection is associated with a substantial morbidity and mortality burden in adult inpatients.

Background: Human metapneumovirus (hMPV) is one of the leading respiratory viruses. This prospective observational study aimed to describe the clinical features and the outcomes of hMPV-associated lower respiratory tract infections in adult inpatients. Methods: Consecutive adult patients admitted to one of the 31 participating centers with an acute lower respiratory tract infection and a respiratory multiplex PCR positive for hMPV were included. A primary composite end point of complicated course (hospital death and/or the need for invasive mechanical ventilation) was used. Results: Between March 2018 and May 2019, 208 patients were included. The median age was 74 [62-84] years. Ninety-seven (47 %) patients were men, 187 (90 %) had at least one coexisting illness, and 67 (31 %) were immunocompromised. Median time between first symptoms and hospital admission was 3 [2-7] days. The two most frequent symptoms were dyspnea (86 %) and cough (85 %). The three most frequent clinical diagnoses were pneumonia (42 %), acute bronchitis (20 %) and acute exacerbation of chronic obstructive pulmonary disease (16 %). Among the 52 (25 %) patients who had a lung CT-scan, the most frequent abnormality was ground glass opacity (41 %). While over four-fifths of patients (81 %) received empirical antibiotic therapy, a bacterial coinfection was diagnosed in 61 (29 %) patients. Mixed flora (16 %) and enterobacteria (5 %) were the predominant documentations. The composite criterion of complicated course was assessable in 202 (97 %) patients, and present in 37 (18 %) of them. In the subpopulation of pneumonia patients (42 %), we observed a more complicated course in those with a bacterial coinfection (8/24, 33 %) as compared to those without (5/60, 8 %) (p = 0.02). Sixty (29 %) patients were admitted to the intensive care unit. Among them, 23 (38 %) patients required invasive mechanical ventilation. In multivariable analysis, tachycardia and alteration of consciousness were identified as risk factors for complicated course. Conclusion: hMPV-associated lower respiratory tract infections in adult inpatients mostly involved elderly people with pre-existing conditions. Bacterial coinfection was present in nearly 30 % of the patients. The need for mechanical ventilation and/or the hospital death were observed in almost 20 % of the patients.

Ventilator-associated pneumonia related to extended-spectrum beta-lactamase producing Enterobacterales during severe acute respiratory syndrome coronavirus 2 infection: risk factors and prognosis.

BACKGROUND: Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring mechanical ventilation suffer from a high incidence of ventilator associated pneumonia (VAP), mainly related to Enterobacterales. Data regarding extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E) VAP are scarce. We aimed to investigate risk factors and outcomes of ESBL-E related VAP among critically ill coronavirus infectious disease-19 (COVID-19) patients who developed Enterobacterales related VAP. PATIENTS AND METHODS: We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU) that included 4929 COVID-19 critically ill patients. For the present analysis, only patients with complete data regarding resistance status of the first episode of Enterobacterales related VAP (ESBL-E and/or carbapenem-resistant Enterobacterales, CRE) and outcome were included. RESULTS: We included 591 patients with Enterobacterales related VAP. The main causative species were Enterobacter sp (n = 224), E. coli (n = 111) and K. pneumoniae (n = 104). One hundred and fifteen patients (19%), developed a first ESBL-E related VAP, mostly related to Enterobacter sp (n = 40), K. pneumoniae (n = 36), and E. coli (n = 31). Eight patients (1%) developed CRE related VAP. In a multivariable analysis, African origin (North Africa or Sub-Saharan Africa) (OR 1.7 [1.07-2.71], p = 0.02), time between intubation and VAP (OR 1.06 [1.02-1.09], p = 0.002), PaO2/FiO2 ratio on the day of VAP (OR 0.997 [0.994-0.999], p = 0.04) and trimethoprim-sulfamethoxazole exposure (OR 3.77 [1.15-12.4], p = 0.03) were associated with ESBL-E related VAP. Weaning from mechanical ventilation and mortality did not significantly differ between ESBL-E and non ESBL-E VAP. CONCLUSION: ESBL-related VAP in COVID-19 critically-ill patients was not infrequent. Several risk factors were identified, among which some are modifiable and deserve further investigation. There was no impact of resistance of the first Enterobacterales related episode of VAP on outcome.

Estimating SARS-CoV-2 infection probabilities with serological data and a Bayesian mixture model.

The individual results of SARS-CoV-2 serological tests measured after the first pandemic wave of 2020 cannot be directly interpreted as a probability of having been infected. Plus, these results are usually returned as a binary or ternary variable, relying on predefined cut-offs. We propose a Bayesian mixture model to estimate individual infection probabilities, based on 81,797 continuous anti-spike IgG tests from Euroimmun collected in France after the first wave. This approach used serological results as a continuous variable, and was therefore not based on diagnostic cut-offs. Cumulative incidence, which is necessary to compute infection probabilities, was estimated according to age and administrative region. In France, we found that a "negative" or a "positive" test, as classified by the manufacturer, could correspond to a probability of infection as high as 61.8% or as low as 67.7%, respectively. "Indeterminate" tests encompassed probabilities of infection ranging from 10.8 to 96.6%. Our model estimated tailored individual probabilities of SARS-CoV-2 infection based on age, region, and serological result. It can be applied in other contexts, if estimates of cumulative incidence are available.

Impact of the COVID-19 Pandemic on COPD Patient Mortality: A Nationwide Study in France.

Objectives: We investigated the mortality patterns of chronic obstructive pulmonary disease (COPD) patients in France relative to a control population, comparing year 2020 to pre-pandemic years 2017-2019. Methods: COPD patient and sex, age and residence matched control cohorts were created from the French National Health Data System. Survival was analyzed using Cox regressions and standardized rates. Results: All-cause mortality increased in 2020 compared to 2019 in the COPD population (+4%), but to a lesser extent than in the control population (+10%). Non-COVID-19 mortality decreased to a greater extent in COPD patients (-5%) than in the controls (-2%). Death rate from COVID-19 was twice as high in the COPD population relative to the control population (547 vs. 279 per 100,000 person-years). Conclusion: The direct impact of the pandemic in terms of deaths from COVID-19 was much greater in the COPD population than in the control population. However, the larger decline in non-COVID-19 mortality in COPD patients could reflect a specific protective effect of the containment measures on this population, counterbalancing the direct impact they had been experiencing.

Direct and indirect impact of the COVID-19 pandemic on the survival of kidney transplant recipients: A national observational study in France.

During the pandemic period, health care systems were substantially reorganized for managing COVID-19 cases. Corresponding consequences on persons with chronic diseases remain insufficiently documented. This observational cohort study investigated the direct and indirect impact of the pandemic period on the survival of kidney transplant recipients (KTR). Using the French National Health Data System, incident persons with end-stage kidney disease between 2015 and 2020, and who received a kidney transplant during this period were included and followed up from their transplantation date to December 31, 2021. The survival of KTR during the prepandemic and pandemic periods was investigated using Cox models with time-dependent covariates. There were 10 637 KTR included in the study, with 324 and 430 deaths observed during the prepandemic and pandemic periods, respectively. The adjusted risk of death during the pandemic period was similar to that observed during the prepandemic period (hazard ratio [HR] [95% confidence interval]: 0.92 [0.77-1.11]), COVID-19-related hospitalization was associated with an increased risk of death (HR: 10.62 [8.46-13.33]), and a third vaccine dose was associated with a lower risk of death (HR: 0.42 [0.30-0.57]). The pandemic period was not associated with an indirect higher risk of death in KTR with no COVID-19-related hospitalization.

In-hospital outcomes after acute myocardial infarction with obstructive coronary artery disease in critically ill patients hospitalized for non-cardiac disease.

BACKGROUND: Acute myocardial infarction (AMI) is one of the major cardiac complications in patients hospitalized in the intensive care unit (ICU) for non-cardiac disease. A better knowledge of ischemic and bleeding risks in these patients is needed to identify those most likely to benefit from specific cardiac management. We therefore assessed the incidence and predictors of a composite outcome of severe ischemic event (AMI recurrence, ischemic stroke), major bleeding, or all-cause death in this setting. METHODS: In this multicenter retrospective study, all consecutive adult patients admitted for non-cardiac disease to four French university hospital ICUs between January 2012 and December 2018 who had an AMI with obstructive coronary artery disease (OCAD) during the ICU stay were considered for inclusion. AMI with OCAD was defined as an elevated cardiac troponin value associated with at least one sign (clinical, electrocardiographic, or echocardiographic) suggestive of myocardial ischemia and presence of OCAD on coronary angiography. The primary endpoint was in-hospital occurrence of the composite outcome. RESULTS: Ninety-six patients [median age 69 years, 22 women (23%), 59 with sepsis (61%), 35 with ST elevation (37%), median sequential organ failure assessment (SOFA) of 8 on the day of AMI] were included. The median peak cardiac troponin value was 131 (IQR 44-303) times the upper reference limit. Dual antiplatelet, therapeutic anticoagulation, and early mechanical reperfusion therapies were administered in 61 (64%), 68 (71%), and 47 (49%) patients, respectively. The composite outcome occurred in 48 (50%) patients. Severe ischemic events occurred in 17 (18%) patients and major bleeding in 26 (27%) patients; 26 patients (27%) died in the hospital. AMI management was not significantly different in patients with and without the composite outcome. A history of arterial hypertension (HR 2.05, 95% CI 1.01-4.16) and high SOFA score at the time of AMI (HR 1.07, 95% CI 1.00-1.15) were independent risk factors for the composite outcome. CONCLUSIONS: Patients who have an AMI with OCAD during an ICU stay for non-cardiac disease are at risk of a composite outcome of severe ischemia, major bleeding, and death. A history of arterial hypertension and high SOFA scores were independent hazards for poor prognosis.

Risk factors and prognostic significance of infection of totally implantable vascular access port in solid tumor patients: A prospective cohort study.

OBJECTIVES: Totally implantable venous access ports (TIVAP) are devices mainly used to deliver antineoplastic chemotherapies, of which the insertion may be complicated by TIVAP-related infection (TIVAP-RI). This study aims to provide data on the risk factors for TIVAP-RI and its influence on patient prognosis. PATIENTS AND METHODS: Prospective observational study including adult patients with solid tumors, in whom a TIVAP was inserted to deliver antineoplastic chemotherapy between January 2018 and October 2019. Factors associated with TIVAP-RI and one-year mortality were determined using multiple logistic regressions. RESULTS: More than a thousand (1014) patients were included, among whom 48 (4.7%) presented with TIVAP-RI. Gram-positive cocci and Gram-negative bacilli represented 51% and 41% of the pathogens isolated, respectively. Young age (odds ratio [OR] 0.67; 95% Confidence Interval [0.53-0.83] per 10-year increase), WHO performance status ≥ 1 (OR 3.24 [1.52-7.79]), chemotherapy administration in the month before TIVAP placement (OR 2.26 [1.17-4.26]), and radiation therapy of the homolateral chest wall (OR 3.28 [1.51-6.67]) were independently associated with TIVAP-RI occurrence. During the year following TIVAP insertion, 287 (28%) patients died. TIVAP-RI was not associated with one-year mortality (OR 1.56 [0.75-3.19]). CONCLUSION: TIVAP insertion in adult patients with solid tumors is associated with a low infection rate, which did not influence one-year mortality. In addition to young age and impaired health status, TIVAP insertion in the month following initiation of the antineoplastic chemotherapy and TIVAP insertion in an irradiated area are two newly reported preventable TIVAP-RI risk factors.

Updating mortality risk estimation in intensive care units from high-dimensional electronic health records with incomplete data.

BACKGROUND: The risk of mortality in intensive care units (ICUs) is currently addressed by the implementation of scores using admission data. Their performances are satisfactory when complications occur early after admission; however, they may become irrelevant in the case of long hospital stays. In this study, we developed predictive models of short-term mortality in the ICU from longitudinal data. METHODS: Using data collected throughout patients' stays of at least 48 h from the MIMIC-III database, several statistical learning approaches were compared, including deep neural networks and penalized regression. Missing data were handled using complete-case analysis or multiple imputation. RESULTS: Complete-case analyses from 19 predictors showed good discrimination (AUC > 0.77 for several approaches) to predict death between 12 and 24 h onward, yet excluded 75% of patients from the initial target cohort, as data was missing for some of the predictors. Multiple imputation allowed us to include 70 predictors and keep 95% of patients, with similar performances. CONCLUSION: This proof-of-concept study supports that automated analysis of electronic health records can be of great interest throughout patients' stays as a surveillance tool. Although this framework relies on a large set of predictors, it is robust to data imputation and may be effective early after admission, when data are still scarce.

The NAFLD burden on mortality and morbidities in general population: A community-based longitudinal study (NASH-CO study).

BACKGROUND: The impact of non-alcoholic fatty liver disease (NAFLD) on morbidity and mortality has yet to be documented at the general population level. This study aimed to assess whether NAFLD was associated with morbidities and mortality and to estimate its impact on health status and mortality. METHODS: The study population consisted of 137 206 participants from Constances cohort. Non-invasive diagnosis of NAFLD and advanced fibrosis was performed using the fatty liver index and Forns index, respectively. Constances data were linked to health care and hospitalization data to identify liver-related events, cardiovascular diseases (CVD), extrahepatic cancers (EHC), chronic kidney disease (CKD) and all-cause mortality. RESULTS: The prevalence of NAFLD was 18.3% in subjects without other chronic liver diseases, among whom 2.7% had fibrosis. NAFLD after IPTW-weighted remained associated with an increased risk of death (HR 1.26, 95% CI 1.01-1.57), hepatic-related complications (HR 2.48, 95% CI 1.99-3.29), CVD (HR 1.42, 95% CI 1.30-1.55), EHC (HR 1.11, 95% CI 1.01-1.28) and CKD (HR 1.81, 95% CI 1.53-2.07) compared to those without chronic liver diseases risk factors (Non-NAFLD). In the trend analysis over the study period of inclusion and compared to Non-NAFLD, NAFLD has shown a fastest growing cause of hepatic events (HR 1.38, 95% CI 1.07-1.76 per year), CVD (HR 1.08, 95% CI 1.03-1.12), CKD (HR 1.16, 95% CI 1.07-1.25), and death (HR 1.39, 95% CI 1.39-1.50). CONCLUSION: This large community-based cohort showed that NAFLD was associated with excess morbidity and mortality and demonstrated a fastest-growing trend.

Cost-effectiveness analysis of direct admission to acute geriatric unit versus admission after an emergency department visit for elderly patients.

BACKGROUND: Elderly individuals represent an increasing proportion of emergency department (ED) users. In the Greater Paris University Hospitals (APHP) direct-admission study, direct admission (DA) to an acute geriatric unit (AGU) was associated with a shorter hospital length of stay (LOS), lower post-acute care transfers, and lower risk of an ED return visit in the month following the AGU hospitalization compared with admission after an ED visit. Until now, no economic evaluation of DA has been available. METHODS: We aimed to evaluate the cost-effectiveness of DA to an AGU versus admission after an ED visit in elderly patients. This was conducted alongside the APHP direct-admission study which used electronic medical records and administrative claims data from the Greater Paris University Hospitals (APHP) Health Data Warehouse and involved 19 different AGUs. We included all patients ≥ 75 years old who were admitted to an AGU for more than 24 h between January 1, 2013 and December 31, 2018. The effectiveness criterion was the occurrence of ED return visit in the month following AGU hospitalization. We compared the costs of an AGU stay in the DA versus the ED visit group. The perspective was that of the payer. To characterise and summarize uncertainty, we used a non-parametric bootstrap resampling and constructed cost-effectiveness accessibility curves. RESULTS: At baseline, mean costs per patient were €5113 and €5131 in the DA and ED visit groups, respectively. ED return visit rates were 3.3% (n = 81) in the DA group and 3.9% (n = 160) in the ED group (p = 0.21). After bootstrap, the incremental cost-effectiveness ratio was €-4249 (95%CI= -66,001; +45,547) per ED return visit averted. Acceptability curves showed that DA could be considered a cost-effective intervention at a threshold of €-2405 per ED return visit avoided. CONCLUSION: The results of this cost-effectiveness analysis of DA to an AGU versus admission after an ED visit for elderly patients argues in favor of DA, which could help provide support for public decision making.

Antibody response, associated symptoms and profile of patients presumably infected by SARS-CoV-2 with taste or smell disorders in the SAPRIS multicohort study.

BACKGROUND: Taste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and antibody response intensity associated with taste or smell disorders. METHODS: We used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave. RESULTS: The analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05-1.58] for women), smoking (OR = 1.54 [95% CI 1.13-2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06-1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26-1.36], OR = 1.37 [95% CI 1.33-1.42] and OR = 1.34 [95% CI 1.29-1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea. CONCLUSIONS: Among patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with an antibody response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms.

Association of preoperative COVID-19 and postoperative respiratory morbidity during the Omicron epidemic wave: the DROMIS-22 multicentre prospective observational cohort study.

Background: Preoperative COVID-19 has been associated with excess postoperative morbi-mortality. Consequently, guidelines were developed that recommended the postponement of surgery for at least 7 weeks after the infection. We hypothesised that vaccination against the SARS-CoV-2 and the large predominance of the Omicron variant attenuated the effect of a preoperative COVID-19 on the occurrence of postoperative respiratory morbidity. Methods: We conducted a prospective cohort study in 41 French centres between 15 March and 30 May 2022 (ClinicalTrials NCT05336110), aimed at comparing the postoperative respiratory morbidity between patients with and without preoperative COVID-19 within 8 weeks prior to surgery. The primary outcome was a composite outcome combining the occurrence of pneumonia, acute respiratory failure, unexpected mechanical ventilation, and pulmonary embolism within the first 30 postoperative days. Secondary outcomes were 30-day mortality, hospital length-of-stay, readmissions, and non-respiratory infections. The sample size was determined to have 90% power to identify a doubling of the primary outcome rate. Adjusted analyses were performed using propensity score modelling and inverse probability weighting. Findings: Of the 4928 patients assessed for the primary outcome, of whom 92.4% were vaccinated against the SARS-CoV-2, 705 had preoperative COVID-19. The primary outcome was reported in 140 (2.8%) patients. An 8-week preoperative COVID-19 was not associated with increased postoperative respiratory morbidity (odds ratio 1.08 [95% CI 0.48-2.13]; p = 0.83). None of the secondary outcomes differed between the two groups. Sensitivity analyses concerning the timing between COVID-19 and surgery, and the clinical presentations of preoperative COVID-19 did not show any association with the primary outcome, except for COVID-19 patients with ongoing symptoms the day of surgery (OR 4.29 [1.02-15.8]; p = 0.04). Interpretation: In our Omicron-predominant, highly immunised population undergoing general surgery, a preoperative COVID-19 was not associated with increased postoperative respiratory morbidity. Funding: The study was fully funded by the French Society of Anaesthesiology and Intensive Care Medicine (SFAR).

Lean individuals with NAFLD have more severe liver disease and poorer clinical outcomes (NASH-CO Study).

BACKGROUND AND AIMS: The severity of liver injury and clinical outcomes in lean individuals with NAFLD is a subject of debate and very few studies have been performed in the general population. The aim of this study was to compare subject characteristics and mortality between lean and nonlean NAFLD in a community setting. APPROACH AND RESULTS: The study population included 169,303 participants from the nationwide Constances cohort. Subjects with excessive alcohol consumption, viral hepatitis, or other liver diseases were excluded and 137,206 subjects were analyzed. The diagnosis of NAFLD and fibrosis was performed using the Fatty Liver Index and the Forns Index. The median follow-up was 3.58 years. The prevalence of NAFLD was 5.3% (95% CI: 5.2-5.4) in lean subjects, while 16.3% (95% CI: 15.7-16.8) of NAFLD subjects were lean. Despite their better metabolic profile, the prevalence of advanced fibrosis was significantly higher in lean than in nonlean NAFLD (3.7% vs. 1.7%, respectively, p < 0.01). Among NAFLD subjects and after adjustment for demographics, metabolic risk factors and lifestyle, lean status was associated with advanced fibrosis (OR=1.26, 95% CI: 1.20-1.65, p = 0.005), an increased risk of liver-related events (adjusted HR=5.84, 95% CI: 4.03-8.46), chronic kidney disease (adjusted HR=2.49, 95% CI: 1.49-4.16), and overall mortality (adjusted HR=3.01, 95% CI: 2.21-4.11). Liver-related events and overall mortality were related to the severity of fibrosis, both in lean and nonlean NAFLD subjects, whatever the usual risk factors. CONCLUSION: This study in a large community-based cohort confirms that NAFLD in lean subjects is more severe for fibrosis, the progression of liver disease, chronic kidney disease, and overall mortality.

Performance of algorithms for identifying patients with chronic hepatitis B or C infection in the french health insurance claims databases using the ANRS CO22 HEPATHER cohort.

The validity of algorithms for identifying patients with chronic hepatitis B or C virus (HBV or HCV) infection in claims databases has been little explored. The performance of 15 algorithms was evaluated. Data from HBV- or HCV-infected patients enrolled between August 2012 and December 2015 in French hepatology centres (ANRS CO22 HEPATHER cohort) were individually linked to the French national health insurance system (SNDS). The SNDS covers 99% of the French population and contains healthcare reimbursement data. Performance metrics were calculated by comparing the viral status established by clinicians with those obtained with the algorithms identifying chronic HBV- and HCV-infected patients. A total of 14 751 patients (29% with chronic HBV and 63% with chronic HCV infection) followed-up until December 2018 were selected. Despite good specificity, the algorithms relying on ICD-10 codes performed poorly. By contrast, the multi-criteria algorithms combining ICD-10 codes, antiviral dispensing, laboratory diagnostic tests (HBV DNA or HCV RNA detection and quantification, HCV genotyping), examinations for the assessment of liver fibrosis and long-term disease registrations were the most effective (sensitivity 0.92, 95% CI, 0.91-0.93 and specificity 0.96, 95% CI, 0.95-0.96 for identifying chronic HBV-infected patients; sensitivity 0.94, 95% CI, 0.94-0.94 and specificity 0.85, 95% CI, 0.84-0.86 for identifying chronic HCV-infected patients). In conclusion, the multi-criteria algorithms perform well in identifying patients with chronic hepatitis B or C infection and can be used to estimate the magnitude of the public health burden associated with hepatitis B and C in France.

Epidemiology, risk factors and prognosis of ventilator-associated pneumonia during severe COVID-19: Multicenter observational study across 149 European Intensive Care Units.

BACKGROUND: COVID-19 patients requiring mechanical ventilation are particularly at risk of developing ventilator-associated pneumonia (VAP). Risk factors and the prognostic impact of developing VAP during critical COVID-19 have not been fully documented. METHODS: Patients invasively ventilated for at least 48 h from the prospective multicentre COVID-ICU database were included in the analyses. Cause-specific Cox regression models were used to determine factors associated with the occurrence of VAP. Cox-regression multivariable models were used to determine VAP prognosis. Risk factors and the prognostic impact of early vs. late VAP, and Pseudomonas-related vs. non-Pseudomonas-related VAP were also determined. MAIN FINDINGS: 3388 patients were analysed (63 [55-70] years, 75.8% males). VAP occurred in 1523/3388 (45.5%) patients after 7 [5-9] days of ventilation. Identified bacteria were mainly Enterobacteriaceae followed by Staphylococcus aureus and Pseudomonas aeruginosa. VAP risk factors were male gender (Hazard Ratio (HR) 1.26, 95% Confidence Interval [1.09-1.46]), concomitant bacterial pneumonia at ICU admission (HR 1.36 [1.10-1.67]), PaO2/FiO2 ratio at intubation (HR 0.99 [0.98-0.99] per 10 mmHg increase), neuromuscular-blocking agents (HR 0.89 [0.76-0.998]), and corticosteroids (HR 1.27 [1.09-1.47]). VAP was associated with 90-mortality (HR 1.34 [1.16-1.55]), predominantly due to late VAP (HR 1.51 [1.26-1.81]). The impact of Pseudomonas-related and non-Pseudomonas-related VAP on mortality was similar. CONCLUSION: VAP affected almost half of mechanically ventilated COVID-19 patients. Several risk factors have been identified, among which modifiable risk factors deserve further investigation. VAP had a specific negative impact on 90-day mortality, particularly when it occurred between the end of the first week and the third week of ventilation.

Impact of direct-acting antiviral treatment for hepatitis C on cardiovascular diseases and extrahepatic cancers.

PURPOSE: The impact of direct-acting antivirals (DAAs) on extrahepatic complications in chronic hepatitis C (CHC) patients remains poorly described. We estimated the association of DAAs with cardiovascular events and extrahepatic cancers. METHODS: The prospective ANRS CO22 HEPATHER cohort was enriched with individual data until December 2018 from the French Health Insurance Database (SNDS). CHC patients were enrolled between August 2012 and December 2015 in 32 French hepatology centers. A total of 8148 CHC adults were selected. Cardiovascular events (stroke, acute coronary syndrome, pulmonary embolism, heart failure, arrhythmias and conduction disorders [ACD], peripheral arterial disease [PAD]) and extrahepatic solid cancers were derived from the SNDS. Associations between DAAs and extrahepatic events were estimated using marginal structural models, with adjustments for clinical confounders. RESULTS: Analyses of 12 905 person-years of no DAA exposure and 22 326 person-years following DAA exposure showed a decreased risk of PAD after DAA exposure (hazard ratio [HR], 0.54; 95% CI, 0.33-0.89), a beneficial effect of DAAs on overall cardiovascular outcomes in patients with advanced fibrosis (aHR, 0.58; 95% CI, 0.42-0.79), and an increased risk of ACD (hazard ratio [HR], 1.46; 95% CI, 1.04-2.04), predominant after the first year following DAA initiation. There was no association between DAAs and extrahepatic cancer risk (HR, 1.23; 95% CI, 0.50-3.03). CONCLUSIONS: DAAs were not associated with extrahepatic cancer development or reduction. They were associated with a decreased risk of PAD and an increased risk of ACD, supporting long-term cardiac monitoring after DAA therapy.

Orthopoxvirus Seroprevalence and Infection Susceptibility in France, Bolivia, Laos, and Mali.

To determine a demographic overview of orthopoxvirus seroprevalence, we tested blood samples collected during 2003-2019 from France (n = 4,876), Bolivia (n = 601), Laos (n = 657), and Mali (n = 255) for neutralizing antibodies against vaccinia virus. In addition, we tested 4,448 of the 4,876 samples from France for neutralizing antibodies against cowpox virus. We confirmed extensive cross-immunity between the 2 viruses. Seroprevalence of antibodies was <1% in Bolivia, <5% in Laos, and 17.25% in Mali. In France, we found low prevalence of neutralizing antibodies in persons who were unvaccinated and vaccinated for smallpox, suggesting immunosenescence occurred in vaccinated persons, and smallpox vaccination compliance declined before the end of compulsory vaccination. Our results suggest that populations in Europe, Africa, Asia, and South America are susceptible to orthopoxvirus infections, which might have precipitated the emergence of orthopoxvirus infections such as the 2022 spread of monkeypox in Europe.