Hazard estimation for censored data contaminated with additive measurement error: application to length of pregnancy

International audienceWe consider random variables which can be subject to both censoring and measurement errors. We focus on the case where the measurement errors affect both the variable of interest and the censoring variable, which is the case of the timing of spontaneous delivery among pregnant women. We propose an estimation strategy to estimate the hazard rate of the underlying variable of interest. We explain the model and this strategy and provide L2-risk bound for the data driven resulting estimator. Simulations illustrate the performances of the estimator. Lastly, the method is applied to a real data set of length of pregnanc

Deconvolution estimation of onset of pregnancy with replicate observations

International audienceExcept in the specific case of in vitro fertilization, the precise date of onset of pregnancy is unknown. In clinical practice, the date of pregnancy may only be estimated, and most commonly from ultrasound biometric measurements of the embryo. Denoting $X$ the interval between last menstrual period and true onset of pregnancy and $Y$ the interval between last menstrual period and the date estimated by ultrasound, we wish to estimate the density \fx of $X$. Only noisy observations $Y_{j}=X_{j}+\varepsilon_{j}, j=1,\dots,n$ are observed and the density $f_\varepsilon$ of $\varepsilon$ is unknown. Because the noise itself cannot be sampled for the estimation of its density, we consider the specific setting of replicate noisy observations $Y_{-j1}=X_{-j}+\varepsilon_{-j1}$ and $Y_{-j2}=X_{-j}+\varepsilon_{-j2}$, $j=1,\dots,M$. We suggest an adaptive non-parametric estimator of \fx built following a deconvolution device. Convergence rates are studied and compared to other settings that do not involve replicates. Lastly, we estimate the density \fx in spontaneous pregnancies with an estimation of the noise obtained from replicate observations in twin pregnancies

Maternal outcomes and risk factors for COVID-19 severity among pregnant women.

Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n = 53/75)], preterm delivery [62.7% (n = 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n = 31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Pronostic de la hernie de coupole diaphragmatique

La hernie de coupole diaphragmatique est une pathologie foetale grave touchant un enfant né vivant sur 3000. Elle est responsable d une mortalité et d une morbidité importante. Elle fait partie des rares pathologies foetales bénéficiant d un traitement in utéro. L un des enjeux majeurs de la prise en charge est l évaluation anténatale du pronostic de ces enfants. De nombreux facteurs pronostiques prénataux existent afin de prédire le taux de survie. L hypertension artérielle pulmonaire est la principale cause de mortalité et de morbidité chez ces enfants. La prédiction de manière fiable de l hypertension artérielle reste pour le moment difficile. Nous avons réalisé une étude rétrospective portant sur les cas de hernie de coupole diaphragmatique à la maternité de Necker entre 2004 et 2010. Nous avons montré qu il était possible de prédire l hypertension artérielle pulmonaire en combinant des marqueurs simples tel que le LHR o/a, le volume pulmonaire à l IRM et la position du foie.ST QUENTIN EN YVELINES-BU (782972101) / SudocSudocFranceF

Optimization of a Sequential Decision Making Problem for a Rare Disease Diagnostic Application

International audienc