A mixed method review and quality criteria analysis : towards improving decision aids and informing care models in prenatal testing

Introduction: Les incertitudes des pronostics cliniques et les dilemmes moraux associés aux technologies des tests prénataux affectent les expériences et les processus décisionnels des femmes et des couples. D’une part, la validité des normes relatives au ‘consentement autonome’ et au conseil ‘non directif’ est remise en question. D’autre part, les aides à la décision sont prônées pour rehausser la prise de décision éclairée. L’objectif de ce mémoire est de construire un modèle de l’expérience des femmes et des couples qui font face aux tests prénataux afin d’identifier les facteurs qui amélioreraient les expériences, la prise de décision et le rôle des aides à la décision et informeraient le modèle de soin. Méthodologie: La modélisation et l’analyse des expériences des femmes et des couples qui affrontent les tests prénataux reposent sur une méta-ethnographie des études qualitatives et sur une analyse narrative thématique des études quantitatives. La critique d’un outil (PT) en matière de tests prénataux est également effectuée en ayant recours aux critères de qualité de l’International Patient Decision Aid Standards (IPDAS). Résultats: Un cadre conceptuel décrivant les expériences vécues est construit et l’analyse thématique le complète en soulignant que la prise de décision n’est que rarement éclairée. Les normes d’une ‘décision autonome’ et d’un ‘conseil non directif’ sont problématiques pour les femmes. Les aides à la décision amélioraient les scores de connaissances, sans pour autant modifier la perception du risque, ni les niveaux d'anxiété. L’outil PT favorise une prise de décision basée sur les préférences, mais les critères IPDAS sont difficilement applicables et leur rôle dans une décision de qualité est incertain. Discussion et conclusion: Les résultats éclairent les facteurs macro, méso et micro pouvant améliorer les expériences vécues des femmes et des couples et affecter la prise de décision et l’utilisation des aides à la décision. Un changement de paradigme préconisant le concept d’autonomie relationnelle dans le modèle de soins est suggéré. Dans le contexte des avancées en matière de test prénataux, une réévaluation des normes de pratique et de modèles de soin est requise. Le rôle des aides à la décision devra être élucidé.Introduction: The clinical prognostic uncertainties and moral dilemmas associated with technological advances of prenatal testing impact the experiences and decision-making of women and couples. While the validity of the norms of ‘autonomous consent’ and ‘non-directive’ counseling is being questioned, decision aids are promoted to enhance informed decision-making. The goals of this thesis are to develop a model of the experiences of women and couples in prenatal testing so as to identify factors that may improve experiences, decision-making, the role of decision aids and inform the care model. Methods: A model of the experiences of prenatal testing is developed through a meta-ethnography of qualitative studies and a narrative synthesis of the themes explored in quantitative studies. A prenatal testing (PT) decision tool is critically assessed using the International Patient Decision Aids Standards (IPDAS) quality criteria for decision aids. Results: A conceptual framework of the experiences of women and couples in prenatal diagnosis is constructed and complemented by a narrative thematic analysis showing that decision-making is rarely informed and that the norms of an ‘autonomous decision’ and a ‘non-directive’ counselling are problematic for women. Decision aids improve knowledge scores, but do no modify risk perception or anxiety levels. A PT tool increases preference based informed decision-making, but quality criteria are not always applicable and their role in quality decision-making is unclear. Discussion and conclusion: The results highlight macro, meso and micro-level factors that may improve the experiences of women and couples and inform decision-making processes as well as the use of decision aids. A paradigm shift towards the concept of relational autonomy in the prenatal diagnosis model of care is suggested. Advances in prenatal testing require a re-evaluation of the norms of practice and care model. The role of decision aids requires further elucidation

Potential brain language reorganization in a boy with refractory epilepsy; an fNIRS–EEG and fMRI comparison

As part of a presurgical investigation for a resection of a tumor located in the left temporal brain region, we evaluated pre- and postsurgical language lateralization in a right-handed boy with refractory epilepsy. In this study, we compared functional near infrared spectroscopy (fNIRS) results obtained while the participant performed expressive and receptive language tasks with those obtained using functional magnetic resonance imaging (fMRI). This case study illustrates the potential for NIRS to contribute favorably to the localization of language functions in children with epilepsy and cognitive or behavioral problems and its potential advantages over fMRI in presurgical assessment. Moreover, it suggests that fNIRS is sensitive in localizing an atypical language network or potential brain reorganization related to epilepsy in young patients

High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies

Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequencing (WGS) in 197 individuals with unexplained DEE and pharmaco-resistant seizures and in their unaffected parents. We focused our attention on de novo mutations (DNMs) and identified candidate genes containing such variants. We sought to identify additional subjects with DNMs in these genes by performing targeted sequencing in another series of individuals with DEE and by mining various sequencing datasets. We also performed meta-analyses to document enrichment of DNMs in candidate genes by leveraging our WGS dataset with those of several DEE and ID series. By combining these strategies, we were able to provide a causal link between DEE and the following genes: NTRK2, GABRB2, CLTC, DHDDS, NUS1, RAB11A, GABBR2, and SNAP25. Overall, we established a molecular diagnosis in 63/197 (32%) individuals in our WGS series. The main cause of DEE in these individuals was de novo point mutations (53/63 solved cases), followed by inherited mutations (6/63 solved cases) and de novo CNVs (4/63 solved cases). De novo missense variants explained a larger proportion of individuals in our series than in other series that were primarily ascertained because of ID. Moreover, these DNMs were more frequently recurrent than those identified in ID series. These observations indicate that the genetic landscape of DEE might be different from that of ID without epilepsy