Chronic use of inhaled corticosteroids in patients admitted for respiratory virus infections: a 6-year prospective multicenter study.

Inhaled corticosteroids (ICS) have been associated with increased risk of pneumonia. Their impact on respiratory virus infections is unclear. We performed a post-hoc analysis of the FLUVAC cohort, a multicenter prospective cohort study of adults hospitalized with influenza-like illness (ILI) during six consecutive influenza seasons (2012-2018). All patients were tested for respiratory virus infection by multiplex PCR on nasopharyngeal swabs and/or bronchoalveolar lavage. Risk factors were identified by logistic regression analysis. Among the 2658 patients included, 537 (20.2%) were treated with ICS before admission, of whom 282 (52.5%, 282/537) tested positive for at least one respiratory virus. Patients on ICS were more likely to test positive for non-influenza respiratory viruses (25.1% vs. 19.5%, P = 0.004), especially for adenovirus (aOR 2.36, 95% CI 1.18-4.58), and respiratory syncytial virus (aOR 2.08, 95% CI 1.39-3.09). Complications were reported in 55.9% of patients on ICS (300/537), primarily pneumonia (171/535, 32%). Among patients on chronic ICS who tested positive for respiratory virus, 14.2% (40/282) were admitted to intensive care unit, and in-hospital mortality rate was 2.8% (8/282). Chronic use of ICS is associated with an increased risk of adenovirus or RSV infections in patients admitted for ILI.

Prognostic performance of endothelial biomarkers to early predict clinical deterioration of patients with suspected bacterial infection and sepsis admitted to the emergency department.

BACKGROUND: The objective of this study was to evaluate the ability of endothelial biomarkers to early predict clinical deterioration of patients admitted to the emergency department (ED) with a suspected sepsis. This was a prospective, multicentre, international study conducted in EDs. Adult patients with suspected acute bacterial infection and sepsis were enrolled but only those with confirmed infection were analysed. The kinetics of biomarkers and organ dysfunction were collected at T0, T6 and T24 hours after ED admission to assess prognostic performances of sVEGFR2, suPAR and procalcitonin (PCT). The primary outcome was the deterioration within 72 h and was defined as a composite of relevant outcomes such as death, intensive care unit admission and/or SOFA score increase validated by an independent adjudication committee. RESULTS: After adjudication of 602 patients, 462 were analysed including 124 who deteriorated (27%). On admission, those who deteriorated were significantly older (73 [60-82] vs 63 [45-78] y-o, p < 0.001) and presented significantly higher SOFA scores (2.15 ± 1.61 vs 1.56 ± 1.40, p = 0.003). At T0, sVEGFR2 (5794 [5026-6788] vs 6681 [5516-8059], p < 0.0001), suPAR (6.04 [4.42-8.85] vs 4.68 [3.50-6.43], p < 0.0001) and PCT (7.8 ± 25.0 vs 5.4 ± 17.9 ng/mL, p = 0.001) were associated with clinical deterioration. In multivariate analysis, low sVEGFR2 expression and high suPAR and PCT levels were significantly associated with early deterioration, independently of confounding parameters (sVEGFR2, OR = 1.53 [1.07-2.23], p < 0.001; suPAR, OR = 1.57 [1.21-2.07], p = 0.003; PCT, OR = 1.10 [1.04-1.17], p = 0.0019). Combination of sVEGFR2 and suPAR had the best prognostic performance (AUC = 0.7 [0.65-0.75]) compared to clinical or biological variables. CONCLUSIONS: sVEGFR2, either alone or combined with suPAR, seems of interest to predict deterioration of patients with suspected bacterial acute infection upon ED admission and could help front-line physicians in the triage process.

Non-influenza respiratory viruses in adult patients admitted with influenza-like illness: a 3-year prospective multicenter study.

PURPOSE: To describe the burden, and characteristics, of influenza-like illness (ILI) associated with non-influenza respiratory viruses (NIRV). METHODS: We performed a prospective, multicenter, observational study of adults admitted with ILI during three influenza seasons (2012-2015). Patients were screened for picornavirus, respiratory syncytial virus (RSV), coronavirus, human metapneumovirus, adenovirus, bocavirus, parainfluenza virus, and influenza, by PCR on nasopharyngeal samples. We excluded patients coinfected with NIRV and influenza. RESULTS: Among 1421 patients enrolled, influenza virus was detected in 535 (38%), and NIRV in 215 (15%), mostly picornavirus (n = 61), RSV (n = 53), coronavirus 229E (n = 48), and human metapneumovirus (n = 40). In-hospital mortality was 5% (NIRV), 4% (influenza), and 5% (no respiratory virus). As compared to influenza, NIRV were associated with age (median, 73 years vs. 68, P = 0.026), chronic respiratory diseases (53% vs. 45%, P = 0.034), cancer (14% vs. 9%, P = 0.029), and immunosuppressive drugs (21% vs. 14%, P = 0.028), and inversely associated with diabetes (18% vs. 25%, P = 0.038). On multivariable analysis, only chronic respiratory diseases (OR 1.5 [1.1-2.0], P = 0.008), and diabetes (OR 0.5 [0.4-0.8], P = 0.01) were associated with NIRV detection. CONCLUSIONS: NIRV are common in adults admitted with ILI during influenza seasons. Outcomes are similar in patients with NIRV, influenza, or no respiratory virus.

Multi-centre evaluation of recent troponin assays for the diagnosis of NSTEMI.

OBJECTIVES: We aimed to compare the use of nine different cardiac troponin (cTn) assays (2 cTnT and 7 cTnI) for the diagnosis of NSTEMI in a single multi-centre population. DESIGN AND METHODS: One hundred and fifty-eight patients were included (mean age 60 years, SD 17 years), including 23 patients (14%) with NSTEMI. RESULTS: The analytical comparison highlighted a large heterogeneity of cTn assays, as reflected by percentages of patients with detectable cTn, correlation coefficients, Passing-Bablok comparisons and concordance coefficients. Correlations within cTnI assays were good and correlation within cTnT assays was excellent. Diagnostic performances demonstrated that each cTn assay has specific threshold values. Furthermore, some assays (HS-cTnI and T, cTnI-Pathfast and cTnI-Centaur) indicated high sensitivity and negative predictive value using the limit of detection (LoD) diagnostic strategy. For the latter assays, a significant increase in specificity was found when using the 99th percentile or the H0-H3 strategies, in comparison to the LoD strategy. When applying the European Society of Cardiology H0-H3 algorithm, comparable diagnostic performances were obtained. CONCLUSION: All 9 cTn assays indicated overall good diagnostic performances for the diagnosis of NSTEMI in emergency departments when the recommended algorithm based on the variation of cTn value between two measurements at admission and 3 h later was used.

[Misuse and adverse effects of new direct oral anticoagulants: A prospective observational study in patients admitted to an emergency unit of a French university hospital]. / Mésusage et iatrogénie des anticoagulants oraux directs (AOD) : étude observationnelle dans le service des urgences du CHU de Limoges.

INTRODUCTION: The use of direct oral anticoagulants (NOAC) is complex: indications, dosage adjustments and precautions. Emergency departments (ED) are increasingly faced with patients receiving NOAC. The aim of this study was to evaluate the misuse and the adverse effects (AE) of NOAC. METHODS: All subjects with NOAC admitted to the Limoges University Hospital ED from 1/8/2013 to 1/4/2014 were included in a prospective observational study. Misuse was identified from the NOAC summary of product characteristics and from the 2014 ANSM guideline (indication, dose, co-medications, age, hepatic and renal function); adverse effects were recorded. RESULTS: A total of 198 subjects were included receiving rivaroxaban (68.7 %), dabigatran (30.8 %) or apixaban (0.5 %). Main indications were embolic prevention in patients with non-valvular atrial fibrillation (78.7 %) and curative treatment of venous thromboembolism (17.2 %). In 16.2 % of the cases, the treatment was not in according to the guidelines: 78 % for prescribing errors (incorrect dosage according to age, renal function, co-medications) and 22 % for wrong initial indication. AE related to NOAC were encountered in 25.8 % patients. Hemorrhagic events were diagnosed in 36 patients with no according to the guidelines in 11.1 % of them. Hemorrhagic events resulted in 3 deaths (8.3 %). Thrombotic events occurred in 15 patients, all these patients were issued with appropriate guidelines. CONCLUSION: Through the view of an ED, this study confirms a part of misuse and highlights the risk of spontaneous bleeding of NOAC despite appropriate use.

Can an early diagnostic procedure of metformin-associated lactic acidosis in an emergency unit reduce mortality?

OBJECTIVE: Metformin-associated lactic acidosis (MALA) is a rare but serious adverse reaction with a mortality rate of up to 50%. Unfortunately, diagnosis and care management are often delayed. The objective was to assess the impact on the mortality rate and length of hospital stay of a MALA early diagnosis procedure in diabetic patients with metformin at emergency department (ED) admission. METHOD: From 1/7/2012, a new MALA diagnosis procedure (pH, lactate, metformin) was implemented in all diabetic patients with metformin just after their admission to the ED. The pharmacovigilance staff confirmed the MALA cases (defined as pH≤7.35, lactate concentration>5mmol/L) in patients exposed to metformin and after a causality assessment to eliminate other common causes of lactic acidosis. To assess the impact of this new diagnosis procedure, a before-after study was conducted between two groups: a series of cases with intervention (IG; 1/7/2012-30/6/2013) and a control series of past cases without intervention (CG; 1/1/2011-30/6/2012). The main outcome was the relative reduction of mortality rate and length of hospital stay between the two groups. RESULTS: Thirty-four MALA cases were confirmed in 745 subjects admitted with lactic acidosis, (IG: 12; CG: 22). A higher illness severity score in the IG vs. CG was observed: respectively arterial lactate (14.2±6.9 vs. 8.8±5.8mmol/L, P<0.05), arterial bicarbonate (7.8±4.3 vs. 14.3±6.3mmol/L, P<0.05). The median time up to MALA diagnosis was 20.5 (Q1-Q3: 11.3-38.5) minutes for IG and 55.0 (Q1-Q3: 33.0-132.0) minutes for CG. After procedure implementation, the mortality relative risk reduction was 26.7% (95% CI: -84.3%, 70.8%), and especially 54.2% (95% CI: -265.2%, 94.2%) in the ED. There was no difference in the hospital stay duration between the two groups. CONCLUSION: While the results were not significant, the study suggests that the implementation of a MALA early diagnosis procedure in all patients with metformin admitted to an ED tends to decrease mortality, especially for serious MALA cases detected earlier.

Determination of ethyl-glucuronide in hair for heavy drinking detection using liquid chromatography-tandem mass spectrometry following solid-phase extraction.

The detection of ethyl-beta-D-6-glucuronide (EtG), a stable phase II metabolite of ethanol, is of interest in both clinical and forensic contexts with the aim of monitoring alcohol abuse. We present a liquid chromatography-electrospray ionisation-tandem mass spectrometry method for the detection and quantification of EtG in hair. Thirty milligrams of washed and cut hair were cleaned up using solid-phase extraction graphite cartridges. Separation was then performed using an Uptisphere-3SI column, and the detection was operated in the negative mode. After validation, the method was applied to hair samples taken from four fatalities (F) with documented excessive drinking habits, 12 heavy drinkers (HD) and seven social drinkers (SD). The method exhibits limits of detection and quantification of 4 and 10 pg/mg, respectively. Intra- and inter-assay standard deviation and relative bias were less than 20% over the calibrating range (10 to 3,000 pg/mg). EtG hair concentrations in SD were <10 pg/mg and >50 pg/mg for F and HD (range, 54 to 497 pg/mg). The present assay appears convenient to carry out owing to the very small quantity of hair samples required to determine an effective heavy alcohol consumption (EtG hair concentration >50 pg/mg).