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Problématique. La thérapie cognitive comportementale (TCC) est la psychothérapie ayant le plus grand support empirique pour les troubles anxieux, et des protocoles de traitement éprouvés sont accessibles pour chaque trouble anxieux. Considérant les similarités tant dans les caractéristiques cliniques (p. ex., appréhension, évitement) que les stratégies d’intervention de TCC (p. ex., restructuration cognitive, exposition) associées aux divers troubles anxieux, la TCC transdiagnostique de groupe (TCCt) pourrait favoriser sa dissémination grâce à l’utilisation d’un protocole unique misant sur ces similarités. But et objectifs. Sur un horizon temporel de huit mois, le but de la thèse est de fournir les premières données quant à la rentabilité de l’ajout de la TCCt aux soins usuels (TCCt+SU) par rapport aux soins usuels seuls (SU) pour les adultes avec des troubles anxieux de la perspective du système de santé et sociétale limitée. Plus précisément, les travaux menés visent à : 1) évaluer les ratios coût-utilité et coût-efficacité incrémentaux (RCUI/RCEI) ; 2) évaluer la probabilité que l’intervention soit rentable selon différents seuils de volonté à payer (SVP) et 3) identifier les prédicteurs et modérateurs de la rentabilité. Méthodologie. Cette évaluation économique s’appuie sur l’essai contrôlé randomisé de Roberge et al. (2018, 2020). Les issues d’efficacité considérées sont le nombre d’années de vie ajustées pour la qualité (AVAQ) selon l’EQ-5D-5L et le nombre de jours sans anxiété (JSA) selon l’Inventaire d’anxiété de Beck. Des données autorapportées ont été collectées sur les coûts directs et indirects associés aux recours aux soins pour des raisons de santé mentale ainsi que sur les coûts déboursés par les personnes participantes. Les RCUI et RCEI ont été calculés pour l’objectif 1 puis le cadre de régression linéaire du bénéfice net a été employé pour répondre aux objectifs 2 et 3. Résultats. Le groupe TCCt+SU (n=117) avait en moyenne plus d’AVAQ et de JSA, ma, Background. Cognitive behavioral therapy (CBT) is the psychotherapy with the greatest empirical support for anxiety disorders, and evidence-based treatment protocols are available for each anxiety disorder. Given the similarities in both clinical features (e.g., apprehension, avoidance) and CBT intervention strategies (e.g., cognitive restructuring, exposure) associated with the various anxiety disorders, transdiagnostic group CBT (tCBT) can be used as a single protocol that builds on these similarities. Purpose and Objectives. The general goal of this thesis was to provide initial data on the cost-effectiveness of adding tCBT to treatment-as-usual (tCBT+TAU) versus treatment-as-usual alone (TAU) for adults with anxiety disorders from the health care system and limited societal perspective and this over an eight-month time horizon. More specifically, the work carried out aimed to: 1) assess the incremental cost-utility and cost-effectiveness ratios (ICUR/ICER); 2) assess the likelihood of the intervention to be cost-effective under different willingness-to-pay thresholds (WTP); and 3) identify predictors and moderators that could influence the cost-effectiveness of the intervention. Methodology. This economic evaluation is based on the randomized controlled trial by Roberge et al. (2018, 2020). The efficacy outcomes considered were quality-adjusted life years (QALYs) according to the EQ-5D-5L and included the number of anxiety-free days (AFD) according to the Beck Anxiety Inventory as an alternative measure. Self-reported data were collected on direct and indirect costs, and out-of-pocket costs, associated with health service use for mental health reasons. The ICUR and ICER were calculated for Objective 1 and then the net benefit regression framework was used to address Objectives 2 and 3. Results. The tCBT+TAU group (n=117) had on average more QALYs and AFDs, but also higher costs from the health system perspective compared with the TAU group (n=114). Th

Résumé : La prééclampsie (PE) est un désordre de la grossesse caractérisée par une dysfonction endothéliale faisant en sorte que l’endothélium devient moins sensible aux signaux de vasodilatation. La réponse provoquée par la liaison de la sérotonine au sous-type de récepteur S[indice inférieur 2] entraîne la libération de molécules aux propriétés vasoconstrictrices, qui, par une boucle de rétroaction positive, entraîne la libération de davantage de sérotonine par les plaquettes. Cette boucle amplifie la réponse et contribue ainsi à l’hypertension présente chez les femmes ayant une PE. Précédemment, il a été démontré par notre laboratoire que le Bisphénol A (BPA) s’accumulait davantage dans le placenta des femmes avec PE en comparaison aux femmes normotensives. Cette accumulation pourrait découler d’une perturbation de sa métabolisation qui impliquerait notamment la β-glucuronidase (GUSB). Des études chez les animaux ont quant à elles démontré que le BPA pouvait inhiber l’activité de la monoamine oxydase (MAO) à forte dose. Nous avons étudié l’effet du BPA à faible concentration (10 ng/ml) sur la MAO-A des cellules placentaires et démontré que le BPA inhibait la MAO-A de façon significative sans affecter son expression protéique. Afin d’expliquer l’accumulation particulière du BPA chez les femmes PE, nous avons comparé l’activité spécifique et l’expression protéique de la β-glucuronidase (GUSB) placentaire en utilisant un devis cas-témoins. Une tendance non significative suggère que la GUSB pourrait partiellement contribuer à l’accumulation du BPA chez les femmes PE. Nous avons étudié la relation entre la concentration sérique maternelle de BPA et la concentration à laquelle le fœtus est exposé par régression linéaire et corrélation de Spearman. Un tel modèle ne pourrait être utilisé pour déterminer de façon quantitative l’exposition fœtale. En revanche, en vue de la forte corrélation entre ces deux variables, une haute concentration sérique maternelle de BPA devrait, Preeclampsia (PE) is an hypertensive disorder of pregnancy characterized by a generalized endothelial dysfunction where the response to vasodilatation signals is compromised. The binding of serotonin to its S[subscript 2] receptor subtype 2 releases vasoconstrictor molecules which, by a positive retroaction loop, stimulates the release of more serotonin from platelets. This positive retroaction loop stimulates the vasoconstriction of blood vessels and contributes to the hypertension in women with PE. Previously, we showed that Bisphenol A (BPA) accumulates more in the placenta of women with PE than in normotensive women. This accumulation may be the result of an impaired metabolization due to the action of the β-Glucuronidase (GUSB). Animal studies showed that BPA at high dose could lower the activity of the monoamine oxidase A (MAO-A), an enzyme implicated in the metabolism of serotonin. We studied the impact of BPA at low dose (10 ng/ml) in trophoblastic primary cells and showed that even at low dose, BPA can lower its activity without affecting the protein expression. To determine if GUSB could be the cause of the BPA accumulation in women with PE, we studied its activity and protein expression in placental biopsies from women with and without PE. A nonsignificant tendency showed that the GUSB activity and protein expression were higher in women with PE. To study the impact of placental metabolism in the fetal exposure, we studied the relation between maternal and fetal concentrations of BPA with linear regression analysis and Spearman’s correlation. We showed that maternal BPA could not precisely predict the fetal exposure and that the placental metabolism is probably limited in light of the strong correlation between both variables. This strong correlation also implied that high maternal exposure would result in high fetal exposure. This study shows that the accumulation of BPA in preeclamptic women could contribute to maternal hypertension by intera

Aim: To assess the impact of sociodemographic factors and beliefs about medicine on the uptake of pharmacogenomic (PGx) testing in older adults in a public healthcare system. Methods: Data is based on a sample of 347 primary care older adults. Results: Most respondents (90%) were willing to provide a saliva sample and 47% were willing to pay for it. Increased age (OR:0.91; p=0.04) and negative beliefs about the harmfulness of medicines (OR: 0.68; p=0.02) were associated with a decreased willingness to provide a sample. Lower education (less than university, OR: 0.54; p=0.04) was associated with a decreased willingness to pay. Conclusions: Education and beliefs about medicines are important factors in the acceptability of PGx testing in older adults.

Background: This economic evaluation supplements a pragmatic randomized controlled trial conducted in community care settings, which showed superior improvement in the symptoms of adults with anxiety disorders who received 12 sessions of transdiagnostic cognitive-behavioural group therapy in addition to treatment as usual (tCBT+TAU) compared to TAU alone. Methods: This study evaluates the cost-utility and cost-effectiveness of tCBT+TAU over an 8-month time horizon. For the reference case, quality-adjusted life years (QALYs) obtained using the EQ-5D-5L, and the health system perspective were chosen. Alternatively, anxiety-free days (AFDs), derived from the Beck Anxiety Inventory, and the limited societal perspective were considered. Unadjusted incremental cost-effectiveness/utility ratios were calculated. Net-benefit regressions were done for a willingness-to-pay (WTP) thresholds range to build cost-effectiveness acceptability curves (CEAC). Sensitivity analyses were included. Results: Compared to TAU (n=114), tCBT+TAU (n=117) generated additional QALYs, AFDs, and higher mental health care costs from the health system perspective. From the health system and the limited societal perspectives, at a WTP of Can$50,000/QALY, the CEACs showed that the probability of tCBT+TAU vs TAU being cost-effective was 97% and 89%. Promising cost-effectiveness results using AFDs are also presented. The participation of therapists from the public health sector could increase cost-effectiveness. Conclusions: From the limited societal and health system perspectives, this first economic evaluation of tCBT shows favourable cost-effectiveness results at a WTP threshold of Can$50,000/QALY. Future research is needed to replicate findings in longer follow-up studies and different health system contexts to better inform decision-makers for a full-scale implementation.