High clinical performance and quantitative assessment of antibody kinetics using a dual recognition assay for the detection of SARS-CoV-2 IgM and IgG antibodies

Objectives: Several serological SARS-CoV-2 immunoassays have been developed recently but require external validation before widespread use. This study aims at assessing the analytical and clinical performance of the iFlash® anti-SARS-CoV-2 chemiluminescence assay for the detection of both IgM and IgG antibodies. The kinetics of the antibody response was also evaluated. Design & Methods: The precision, carry-over, linearity, limit of blank, detection and quantification were assessed. Sensitivity analysis was performed by using 178 sera collected from 154 RT-PCR confirmed COVID-19 patients. The specificity analysis was performed from 75 selected non-SARS-CoV-2 sera with a potential cross-reaction to the SARS-CoV-2 immunoassay. Results: This iFlash® SARS-CoV-2 assay showed excellent analytical performance. After 2 weeks since symptom onset, the sensitivities for IgM and IgG were 62.2% (95% CI: 52.3–71.2%) and 92.9%% (95% CI: 85.7–96.7%), respectively by using the cut-off provided by the manufacturer. After cut-off optimization (i.e. >2.81 for IgM and >4.86 for IgG), the sensitivity for IgM and IgG were 81.6 (95% CI: 72.7–88.1%) and 95.9% (95% CI: 89.4–98.7%), respectively. Optimized cut-off for IgG improved the sensitivity to reach 100% (95%CI: 87.6–100) from 28 days since symptom onset. Conclusions: This study shows that the iFlash® SARS-CoV-2 assay from YHLO biotechnology, has satisfactory analytical performance. Nevertheless, the sensitivity of the IgM is limited for a proper clinical use compared to IgG. The determination of anti-SARS-CoV-2 IgG antibodies from 28 days since symptom onset was associated with high sensitivity, especially using optimized cut-offs (i.e. 100%).SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

L'activité physique des tout-petits

Activités gymniques du jeune enfant : l'aménagement de l'espace d'action favorise l'expérimentation nécessaire à la construction de leurs habiletés motrices. Suivi d'une fiche pédagogique 'J'explore, j'agis', présentant des situations pour explorer l'espace et éprouver des habiletés motrices variées induites par l'aménagement en cycle 1

Allergie aux venins d'insectes

Specific IgE-mediated allergic reactions to hymenoptera venoms (honey bee, wasp) can be systemic and life-threatening. The sting reactions can also be mild and restricted to the skin/mucosa. The prevalence of systemic sting reactions ranged from 0.3 to 7.5 % in adult population and from 14 to 43 % for beekeepers and less common among children (3.5 %). In the case of anaphylaxis, the patient should use quickly an adrenaline auto-injector. In case of severe systemic reaction, venom immunotherapy can be recommended and especially in patients with cardiovascular disease, asthma or mastocytosis. A careful personal history should be taken, venom specific IgE and allergenic molecules should be determined. Venom immunotherapy should be performed for at least five years, after discussion with the patients.SCOPUS: ar.jDecretOANoAutActifinfo:eu-repo/semantics/publishe

Réduction de la durée du travail et chômage : éléments de réflexion en forme de modèle

Mairesse Jacques, Charpin Jean-Michel. Réduction de la durée du travail et chômage : éléments de réflexion en forme de modèle. In: Revue économique, volume 29, n°1, 1978. pp. 189-206

L'activité physique des tout-petits

Activités gymniques du jeune enfant : l'aménagement de l'espace d'action favorise l'expérimentation nécessaire à la construction de leurs habiletés motrices. Suivi d'une fiche pédagogique 'J'explore, j'agis', présentant des situations pour explorer l'espace et éprouver des habiletés motrices variées induites par l'aménagement en cycle 1

Évaluation de l'impact d'un PDU : problématique de l'émission de polluants atmosphériques

The a priori assessment of the Urban Develop- ment Plans (PDU, currently implemented in the main French cities), or of measures aiming at reducing the air pollution from road traffic through travel and traffic management relies on traffic and pollutant emission simulation. The outputs of these simulations can be used thus for estimating air quality as well as health impacts. We examine here the approach for determining the pollutants emissions: involved phenomenon and pollutants, tools, knowledge limits, questions relating to traffic data or to the setting-up of assumptions for a case study. A plate-form for emission calculation (derived from the COPERT European methodology) is applied to the area of the Nantes-Metropole PDU, using simulated travel and traffic data. The estimations demonstrate that the city-left, the peak-hour, or the passenger cars do not represent the main of the emission quantities, according to different pollutants. Light duty vehicles, lorries and buses, which are badly taken into account by the approach, constitute a significant challenge. Cold start overemission is also significant and particulates emissions are uncertain because they are roughly estimated. The assessment of the actual in-use fleet composition is fundamental, as emissions are very sensitive to low differences in term of motorization or emission standards. However local specificities are not known, and the spatial affectation is uncertain. Driving data (speeds) are the other weak point of estimation, being likely overestimated by the traffic models. They should be improved through in situ observations. The identification of such uncertainties should enable improving the assessment approach, through data to reinforce assumptions, and through precautions in the methodology as well as in the results analysis.L'évaluation a priori des Plans de déplacements urbains (PDU) des agglomérations et plus généralement des mesures d'organisation et de gestion des déplacements et du trafic en vue de limiter leurs impacts sur la qualité de l'air repose sur une simulation des trafics et des émissions de polluants, dont les résultats peuvent ensuite être intégrés dans un calcul des concentrations ambiantes et des impacts sanitaires. On examine dans ce cadre la problématique de détermi- nation des émissions de polluants : phénomènes et polluants, outils de calculs, limites des connaissances, questions relatives aux données de trafic et à la transcription d'un cas d'étude en hypothèses. Une plate-forme de calcul des émissions de polluants (approche Computer Program to calculate Emissions from Road Transport (COPERT) 4) est appliquée au territoire du PDU de Nantes Métropole sur les données simulées des déplacements et des trafics. Les estimations montrent que le centre-ville, l'heure de pointe ou encore les voitures particulières ne représentent pas l'essentiel des quantités d'émission selon les polluants. Les véhicules utilitaires légers et camions/bus, relativement mal appréhendés par les modèles constituent un enjeu. Les surémissions de démar- rage à froid sont également très significatives et une grande part d'incertitude concerne les émissions de particules. La problématique du parc automobile est fondamentale, les émissions étant très sensibles à de faibles écarts de composition et d'âge, et cependant, on ne dispose pas de connaissance des parcs locaux ni de leur affectation spatiale précise (véhicules lourds). Les conditions de circulation sont l'autre point faible des approches, avec des estimations peu plausibles des vitesses de circulation, qu'il conviendrait d'améliorer par des données mesurées in situ