Potent P2Y12 Inhibitor Selection and De-escalation Strategies in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention: Systematic Review and Meta-analysis.

Background: Balancing the effects of dual antiplatelet therapy (DAPT) in the era of potent purinergic receptor type Y, subtype 12 (P2Y12) inhibitors remains a challenge in the management of acute coronary syndrome (ACS). Methods: We conducted a systematic review and meta-analysis following a 2-stage process consisting of searching for systematic reviews published between 2019 and November 2022. We included randomized controlled trials (RCTs) of ACS patients treated with percutaneous coronary intervention comparing (i) ticagrelor- vs prasugrel-based DAPT and (ii) P2Y12 inhibitor de-escalation strategies. Outcomes of interest were major adverse cardiovascular events (MACE), all-cause death, stent thrombosis, and major bleeding. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model. Results: Eight RCTs (n = 5571) compared ticagrelor to prasugrel. Ticagrelor was associated with an increased risk of MACE compared to prasugrel (RR 1.23, 95% CI 1.01-1.49, moderate certainty), without significant differences in death, stent thrombosis, or major bleeding. In 2 RCTs (n = 3343) comparing clopidogrel-based DAPT de-escalation after 1 month to potent P2Y12 inhibitor-based DAPT continuation, clopidogrel de-escalation did not significantly alter the incidence of MACE, death, or stent thrombosis, but reduced that of major bleeding (RR 0.51, 95% CI 0.28-0.92, high certainty). The effect of prasugrel dose de-escalation was inconclusive for all outcomes based on one trial. Conclusions: Ticagrelor was associated with an increase in MACE compared with prasugrel, based on low-certainty evidence, whereas de-escalation to clopidogrel after 1 month of potent P2Y12 inhibitor was associated with a decrease in incidence of major bleeding without increasing thrombotic outcomes in ACS patients post-percutaneous coronary intervention.

Contexte: Équilibrer les effets de la bithérapie antiplaquettaire (BTAP) à l'ère des puissants inhibiteurs du récepteur purinergique de type Y, sous-type 12 (P2Y12) demeure un défi dans la prise en charge du syndrome coronarien aigu (SCA). Méthodologie: Nous avons procédé à un examen systématique et à une méta-analyse, tout d'abord en recherchant les revues systématiques publiées entre 2019 et 2022, puis en mettant à jour la recherche la plus complète de ces revues jusqu'en novembre 2022. Nous avons inclus des essais contrôlés randomisés (ECR) menés chez des patients ayant subi un SCA traité par intervention coronarienne percutanée qui comparaient i) une BTAP comportant du ticagrélor à une BTAP à base de prasugrel, et ii) les stratégies de réduction graduelle de la dose de l'inhibiteur de P2Y12. Les résultats d'intérêt comprenaient les événements cardiovasculaires indésirables majeurs (ECIM), les décès toutes causes confondues, les thromboses de l'endoprothèse et les saignements majeurs. Nous avons estimé les rapports de risques (RR) et les intervalles de confiance (IC) à 95 % à l'aide d'un modèle à effets aléatoires. Résultats: Huit ECR (n = 5 571) ont comparé le ticagrélor au prasugrel. Le ticagrélor était associé à un risque accru d'ECIM comparativement au prasugrel (RR de 1,23, IC à 95 % de 1,01 à 1,49, certitude modérée), sans différence significative quant au décès, à la thrombose de l'endoprothèse ou au saignement majeur. Dans deux ECR (n = 3 343) comparant la réduction graduelle de la BTAP à base de clopidogrel après 1 mois à la poursuite de la BTAP comportant un inhibiteur puissant de P2Y12, la réduction graduelle de la dose de clopidogrel n'a pas modifié de manière significative la fréquence des ECIM, des décès ou des thromboses de l'endoprothèse, mais a réduit celle des saignements majeurs (RR de 0,51, IC à 95 % de 0,28 à 0,92, certitude élevée). L'effet de la réduction graduelle de la dose de prasugrel n'a pas été concluant pour tous les résultats sur la base d'un seul essai. Conclusions: Si l'on se fie aux données probantes de faible certitude, le ticagrélor a été associé à une augmentation des ECIM comparativement au prasugrel, tandis que la réduction graduelle de la dose de clopidogrel après 1 mois d'administration d'un puissant inhibiteur de P2Y12 a été associée à une diminution de la fréquence des saignements majeurs sans augmentation des événements thrombotiques chez les patients ayant subi une intervention coronarienne percutanée pour traiter un SCA.

Middle Childhood Sport Participation Predicts Timely Long-Term Chances of Academic Success in Boys and Girls by Late Adolescence.

INTRODUCTION: School age children experience successive academic demands which increase over time. Extracurricular sport develops skills which involve physical movement, social rules, formal practice, and rational competition. This may facilitate success. PURPOSE: Using a prospective-longitudinal birth cohort of 746 girls/721 boys, we examined prospective associations between middle childhood sport participation with subsequent indicators of academic success in adolescence. We hypothesized that persistent participation would promote long-term achievement indicators. METHODS: Mothers reported on whether the child participated in sporting activities with a coach/instructor from ages 6 to 10 years. Developmental trajectories of participation were generated using longitudinal latent class analysis and then used to predict outcomes. From ages 12 to 17 years, youth self-reported on academic indicators of success over the last 6 months. These were linearly regressed on trajectories of participation in sport, while controlling for pre-existing and concurrent child/family confounds. RESULTS: Children's sport participation from kindergarten to fourth grade predicted long-term chances of academic success in boys and girls, above and beyond individual/family confounders. Consistent participation predicted increments indicators of future success and reductions in academic failure and dropout risk through to the senior year of secondary school, ranging from 9.1% to 21.3% for girls and 11.7% to 22.9% for boys. CONCLUSIONS: We provide compelling and timely evidence of long-term associations between children's sport participation and subsequent indicators of academic success in typically developing boys and girls by late adolescence. Persistent sport involvement in sport increased educational prospects by late adolescence, potentially improving opportunities for success in emerging adulthood.

GABA and Glx predict EEG responses of visual sensitivity in autism.

The mechanisms underlying atypical sensory processing in autism remain to be elucidated, but research points toward a role of the glutamatergic/GABAergic balance. To investigate the potential relationships between visual sensitivity and its molecular correlates in autism, we combined data from electroencephalography (EEG) and magnetic resonance spectroscopy (MRS) studies. Twenty autistic adults and sixteen neurotypical adults (NT) participated in both an EEG study assessing visual sensitivity (Sapey-Triomphe et al., Autism Research, 2023) and in an MRS study measuring Glx and GABA+ concentrations in the occipital cortex (Sapey-Triomphe et al., Molecular Autism, 2021). These studies revealed no group differences in neural detection thresholds or in Glx/GABA levels in the occipital cortex. Neural detection thresholds for contrast and spatial frequency (SF) were determined using fast periodic visual stimulations and neural frequency tagging. In the present study, Glx/GABA+ concentrations in the occipital cortex and neural detection thresholds did not differ between groups. Interestingly, lower Glx/GABA+ ratios were associated with lower contrast detection thresholds and higher SF detection thresholds. These correlations were also significant within the neurotypical and autistic groups. This report suggests that the Glx/GABA balance regulates visual detection thresholds across individuals. In both autistic and NTs, lower Glx/GABA ratios in the occipital cortex allow for better detection of visual inputs at the neural level. This study sheds light on the neurochemical underpinnings of visual sensitivity in autism and warrants further investigation.

Pathophysiology of Myocardial Infarction With Nonobstructive Coronary Artery Disease: A Contemporary Systematic Review.

Background: Myocardial infarction with nonobstructive coronary artery disease (MINOCA) is defined as acute myocardial infarction (AMI) with angiographically nonobstructive coronary artery disease. MINOCA represents 6% of all AMI cases and is associated with increased mortality and morbidity. However, the wide array of pathophysiological factors and causes associated with MINOCA presents a diagnostic conundrum. Therefore, we conducted a contemporary systematic review of the pathophysiology of MINOCA. Methods: A comprehensive systematic review of MINOCA was carried out through the utilization of the PubMed database. All systematic reviews, meta-analyses, randomized controlled trials, and cohort studies available in English or French that reported on the pathophysiology of MINOCA published after January 1, 2013 were retained. Results: Of the 600 identified records, 80 records were retained. Central to the concept of MINOCA is the definition of AMI, characterized by the presence of myocardial damage reflected by elevated cardiac biomarkers in the setting of acute myocardial ischemia. As a result, a structured approach should be adopted to thoroughly assess and address clinically overlooked obstructive coronary artery disease, and cardiac and extracardiac mechanisms of myocyte injury. Once these options have been ruled out, a diagnosis of MINOCA can be established, and the appropriate multimodal assessment can be conducted to determine its specific underlying cause (plaque disruption, epicardial coronary vasospasm, coronary microvascular dysfunction, and coronary embolism and/or spontaneous coronary dissection or supply-demand mismatch). Conclusions: Integrating a suitable definition of AMI and understanding the pathophysiological mechanisms of MINOCA are crucial to ensure an effective multimodal diagnostic evaluation and the provision of adequate tailored therapies.

Contexte: L'infarctus du myocarde sans obstruction des artères coronaires (MINOCA) est défini comme un infarctus aigu du myocarde (IAM) en présence d'une coronaropathie non obstructive confirmée par angiographie. Le MINOCA représente 6 % de tous les cas d'IAM et est associé à une hausse des taux de mortalité et de morbidité. Cependant, le large éventail de facteurs physiopathologiques et de causes associés au MINOCA représente une énigme diagnostique. C'est pourquoi nous avons réalisé une analyse systématique des publications contemporaines sur la physiopathologie du MINOCA. Méthodologie: Une analyse exhaustive des publications sur le MINOCA a été menée au moyen de la base de données PubMed. L'ensemble des analyses systématiques, des méta-analyses, des essais contrôlés randomisés et des études de cohorte publiés en anglais ou en français après le 1er janvier 2013 qui faisaient état de la physiopathologie du MINOCA ont été retenus. Résultats: Parmi les 600 dossiers relevés, 80 ont été retenus. La définition de l'IAM était centrale au concept de MINOCA et était caractérisée par la présence d'une lésion myocardique attestée par des taux élevés de biomarqueurs cardiaques en contexte d'ischémie myocardique aiguë. Par conséquent, une approche structurée devrait être adoptée pour évaluer pleinement et traiter les coronaropathies obstructives qui passent inaperçues en clinique ainsi que les mécanismes cardiaques et extracardiaques des lésions aux myocytes. Une fois ces options exclues, un diagnostic de MINOCA peut être établi et l'évaluation multimodale appropriée peut être menée pour déterminer la cause sous-jacente précise (rupture de plaque, vasospasme d'une artère coronaire épicardique, dysfonction microvasculaire coronarienne et embolie coronarienne et/ou dissection spontanée d'une artère coronaire ou déséquilibre entre apports et besoins). Conclusions: Il est crucial d'intégrer une définition convenable de l'IAM et de comprendre les mécanismes physiopathologiques du MINOCA pour assurer une évaluation diagnostique multimodale efficace et une prestation de traitements adaptés et adéquats.

The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 9: Summary of Current Status, Challenges, Opportunities, and Recommendations.

This final chapter of the Canadian Women's Heart Health Alliance "ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women" presents ATLAS highlights from the perspective of current status, challenges, and opportunities in cardiovascular care for women. We conclude with 12 specific recommendations for actionable next steps to further the existing progress that has been made in addressing these knowledge gaps by tackling the remaining outstanding disparities in women's cardiovascular care, with the goal to improve outcomes for women in Canada.

Dans ce chapitre final de l'ATLAS sur l'épidémiologie, le diagnostic et la prise en charge de la maladie cardiovasculaire chez les femmes de l'Alliance canadienne de santé cardiaque pour les femmes, nous présentons les points saillants de l'ATLAS au sujet de l'état actuel des soins cardiovasculaires offerts aux femmes, ainsi que des défis et des occasions dans ce domaine. Nous concluons par 12 recommandations concrètes sur les prochaines étapes à entreprendre pour donner suite aux progrès déjà réalisés afin de combler les lacunes dans les connaissances, en s'attaquant aux disparités qui subsistent dans les soins cardiovasculaires prodigués aux femmes, dans le but d'améliorer les résultats de santé des femmes au Canada.

Antithrombotic Management and Outcomes of Anterior ST-Elevation Myocardial Infarction With New-Onset Wall Motion Abnormalities in Men and Women.

Background: In patients with anterior ST-elevation myocardial infarction (STEMI) and new-onset antero-apical wall motion abnormalities (WMAs), whether the rate of prophylaxis against left ventricular thrombus and outcomes differ between men and women is unknown. Methods: A multicentre retrospective cohort study of patients with STEMI and new-onset antero-apical WMAs treated with primary percutaneous coronary intervention was conducted. Patients with an established indication of oral anticoagulation (OAC) were excluded. The rates of triple therapy (double antiplatelet therapy + OAC) at discharge were compared for women vs men. The rates of net adverse clinical events, a composite of mortality, myocardial infarction, stroke or transient ischemic attack, systemic thromboembolism or Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at 6 months were compared across sex using a multivariate logistic regression model. Results: A total of 1664 patients were included in the primary analysis, of whom 402 (24.2%) were women and 1262 (75.8%) were men. A total of 138 women (34.3%) and 489 men (38.7%) received a triple therapy prescription at discharge (P = 0.11). At 6 months, 33 women (8.2%) and 96 men (7.6%) experienced a net adverse clinical event (adjusted odds ratio 0.82; 95% confidence interval 0.49-1.37). No difference occurred in the risk of bleeding events and ischemic events between men and women, when these were analyzed separately. Conclusions: The rates of OAC prescription for left ventricular thrombus prophylaxis and clinical outcomes at 6 months were similar in women and men following anterior STEMI with new-onset antero-apical WMAs.

Contexte: On ignore si le taux de prophylaxie contre le thrombus ventriculaire gauche et les résultats thérapeutiques diffèrent entre les hommes et les femmes qui ont subi un infarctus du myocarde avec élévation du segment ST (STEMI) antérieur et ont des anomalies du mouvement pariétal (AMP) antéroapical d'apparition récente. Méthodes: Nous avons mené une étude de cohorte rétrospective multicentrique auprès de patients qui ont subi un STEMI et ont des AMP d'apparition récente traitées par une intervention coronarienne percutanée primaire. Nous avons exclu les patients chez lesquels il existait une indication établie à l'anticoagulation orale (ACO). Nous avons comparé les taux de trithérapie (bithérapie antiplaquettaire + ACO) à la sortie de l'hôpital entre les femmes et les hommes. Nous avons comparé les taux d'événements indésirables cliniques nets, le critère composite de mortalité, d'infarctus du myocarde, d'accident vasculaire cérébral ou d'accident ischémique transitoire, la thromboembolie systémique ou l'hémorragie de type 3 ou 5 selon le Bleeding Academic Research Consortium (BARC) après 6 mois entre les sexes au moyen du modèle de régression logistique multivariée. Résultats: Au sein des 1 664 patients de l'analyse principale, 402 (24,2 %) étaient des femmes et 1262 (75,8 %) étaient des hommes. Un total de 138 femmes (34,3 %) et de 489 hommes (38,7 %) ont reçu une ordonnance de trithérapie à la sortie de l'hôpital (P = 0,11). Après 6 mois, 33 femmes (8,2 %) et 96 hommes (7,6 %) ont subi un événement indésirable net (rapport de cotes ajusté 0,82 ; intervalle de confiance à 95 % 0,49-1,37). Aucune différence n'a été notée dans le risque d'événements hémorragiques et d'événements ischémiques entre les hommes et les femmes lorsque ces événements étaient analysés séparément. Conclusions: Les taux d'ordonnances d'ACO en prophylaxie du thrombus ventriculaire gauche et les résultats cliniques après 6 mois étaient similaires entre les femmes et les hommes à la suite du STEMI antérieur et des AMP antéroapicale d'apparition récente.

Partners with a Highly Favorable Attitude Toward Breastfeeding Contribute to Promoting Initiation and Length of Breastfeeding for More than 5 Months in a Population-Based Canadian Study.

Introduction: Promoting maternal breastfeeding for at least 6 months is important to improve children physical health during infancy and neurodevelopmental outcomes in childhood. For this guideline to be followed, it is paramount to identify what factors best support the initiation and length of breastfeeding. This study estimates the contribution of various child- and parent-level factors, as well as the sociodemographic context in predicting maternal breastfeeding initiation and duration. Methods: This study draws on data from the Quebec Longitudinal Study of Child Development. Mothers who never breastfed when the infant was 5 months old (n = 630, 28.3%) were compared to mothers who breastfed for less than 5 months (n = 844, 38.0%) and mothers breastfeeding for more than 5 months (n = 749, 33.7%), using multivariable multinomial regression models. Results: Mothers with a partner showing a positive attitude toward breastfeeding were up to 13 times more likely to breastfeed their infant for more than 5 months. The positive attitude of partners toward breastfeeding was the strongest predictor of breastfeeding duration, followed by the maternal educational attainment and timing she returns to work. Most prenatal and perinatal child-level factors and the sociodemographic context predicted breastfeeding duration, but to a lesser extent. Discussion: This finding underscores the role of the partner's attitude in promoting initiation and length of breastfeeding. As such, educational campaigns and health practitioners could target both the mother and their partner in promoting breastfeeding.

Cognitive and Motor Function Effects of Antipsychotics in Traumatic Brain Injury: A Systematic Review of Pre-Clinical Studies.

Traumatic brain injury (TBI) survivors often suffer from agitated behaviors and will most likely receive pharmacological treatments. Choosing an optimal and safe treatment that will not interfere with neurological recovery remains controversial. By interfering with dopaminergic circuits, antipsychotics may impede processes important to cognitive recovery. Despite their frequent use, there have been no large randomized controlled studies of antipsychotics for the management of agitated behaviors during the acute TBI recovery period. We conducted a systematic review and meta-analysis of pre-clinical studies evaluating the effects of antipsychotics post-TBI on both cognitive and motor recovery. MEDLINE and Embase databases were searched up to August 2, 2023. Pre-clinical studies evaluating the effects of antipsychotics on cognitive and motor functions post-TBI were considered. Risk of bias was evaluated with the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. We identified 15 studies including a total of 1188 rodents, mostly conducted in male Sprague-Dawley rats using cortical impact injury. The analysis revealed no consistent effect of haloperidol on motor functions, but risperidone was associated with a significant impairment in motor function on day 5 post-injury (7.05 sec; 95% confidence interval [CI]: 1.47, 12.62; I2 = 92%). Other atypical antipsychotics did not result in impaired motor function. When evaluating cognitive function, haloperidol- (23.00 sec; 95% CI: 17.42-28.59; I2 = 7%) and risperidone-treated rats (24.27 sec; 95% CI: 16.18-32.36; I2 = 0%) were consistently impaired when compared to controls. In studies evaluating atypical antipsychotics, no impairments were observed. Clinicians should avoid the regular use of haloperidol and risperidone, and future human studies should be conducted with atypical antipsychotics.

Antipsychotics and Risks of Cardiovascular and Cerebrovascular Diseases and Mortality in Dwelling Community Older Adults.

This study aims to investigate the effect of antipsychotic agents on cardiovascular and cerebrovascular diseases (CVD/CEV) and mortality risks in the older population living in a community. A cohort of 42,650 new users of antipsychotic agents was built using Quebec healthcare databases (1998-2011). The outcomes were CVD/CEV and mortality incidence in 5 years of follow-up in the total cohort, sub-cohort of patients with no schizophrenia/dementia, sub-cohort with schizophrenia, and sub-cohort with dementia. Comparisons were made between the new users who continued the treatment (adherent level ≥ 60%) vs. those ceasing treatment (adherence level < 60%) using inverse probability of treatment weighting and Cox models. Comparing high adherence vs. low levels, CVD/CEV risk was increased by 36% in the sub-cohort with schizophrenia for atypical antipsychotic users and by 25% in the sub-cohort with dementia for typical antipsychotic users. An increasing mortality risk of 2- to 3-fold was linked with the typical antipsychotic use in all cohorts except the sub-cohort with schizophrenia; in addition, mortality risk is linked with the use of high vs. low doses. Antipsychotics were not linked with CVD/CEV risk, except for atypical antipsychotics in patients with schizophrenia and typical antipsychotics in patients with dementia. The mortality risk was linked with the use of typical antipsychotics and the dose used.

Hyperventilation testing in the diagnosis of vasospastic angina: A clinical review and meta-analysis.

BACKGROUND: Given the limited access to invasive vasospastic reactivity testing in Western Countries, there is a need to further develop alternative non-invasive diagnostic methods for vasospastic angina (VSA). Hyperventilation testing (HVT) is defined as a class IIa recommendation to diagnose VSA by the Japanese Society of Cardiology. METHODS: In this systematic review and meta-analysis reported according to the PRISMA statement, we review the mechanisms, methods, modalities and diagnostic accuracy of non-invasive HVT for the diagnostic of VSA. RESULTS: A total of 106 articles published between 1980 and 2022 about VSA and HVT were included in the systematic review, among which 16 were included in the meta-analysis for diagnostic accuracy. Twelve electrocardiogram-HVT studies including 804 patients showed a pooled sensitivity of 54% (95% confidence intervals [CI]; 30%-76%) and a pooled specificity of 99% (95% CI; 88%-100%). Four transthoracic echocardiography-HVT studies including 197 patients revealed a pooled sensitivity of 90% (95% CI; 82%-94%) and a pooled specificity of 98% (95% CI; 86%-100%). Six myocardial perfusion imaging-HVT studies including 112 patients yielded a pooled sensitivity of 95% (95% CI; 63%-100%) and a pooled specificity of 78% (95% CI; 19%-98%). Non-invasive HVT resulted in a low rate of adverse events, ventricular arrhythmias being the most frequently reported, and were resolved with the administration of nitroglycerin. CONCLUSIONS: Non-invasive HVT offers a safe alternative with high diagnostic accuracy to diagnose VSA in patients with otherwise undiagnosed causes of chest pain.

Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology 2023 Focused Update of the Guidelines for the Use of Antiplatelet Therapy.

Antiplatelet therapy (APT) is the foundation of treatment and prevention of atherothrombotic events in patients with atherosclerotic cardiovascular disease. Selecting the optimal APT strategies to reduce major adverse cardiovascular events, while balancing bleeding risk, requires ongoing review of clinical trials. Appended, the focused update of the Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology guidelines for the use of APT provides recommendations on the following topics: (1) use of acetylsalicylic acid in primary prevention of atherosclerotic cardiovascular disease; (2) dual APT (DAPT) duration after percutaneous coronary intervention (PCI) in patients at high bleeding risk; (3) potent DAPT (P2Y12 inhibitor) choice in patients who present with an acute coronary syndrome (ACS) and possible DAPT de-escalation strategies after PCI; (4) choice and duration of DAPT in ACS patients who are medically treated without revascularization; (5) pretreatment with DAPT (P2Y12 inhibitor) before elective or nonelective coronary angiography; (6) perioperative and longer-term APT management in patients who require coronary artery bypass grafting surgery; and (7) use of APT in patients with atrial fibrillation who require oral anticoagulation after PCI or medically managed ACS. These recommendations are all on the basis of systematic reviews and meta-analyses conducted as part of the development of these guidelines, provided in the Supplementary Material.

Disentangling sensory precision and prior expectation of change in autism during tactile discrimination.

Predictive coding theories suggest that core symptoms in autism spectrum disorders (ASD) may stem from atypical mechanisms of perceptual inference (i.e., inferring the hidden causes of sensations). Specifically, there would be an imbalance in the precision or weight ascribed to sensory inputs relative to prior expectations. Using three tactile behavioral tasks and computational modeling, we specifically targeted the implicit dynamics of sensory adaptation and perceptual learning in ASD. Participants were neurotypical and autistic adults without intellectual disability. In Experiment I, tactile detection thresholds and adaptation effects were measured to assess sensory precision. Experiments II and III relied on two-alternative forced choice tasks designed to elicit a time-order effect, where prior knowledge biases perceptual decisions. Our results suggest a subtler explanation than a simple imbalance in the prior/sensory weights, having to do with the dynamic nature of perception, that is the adjustment of precision weights to context. Compared to neurotypicals, autistic adults showed no difference in average performance and sensory sensitivity. Both groups managed to implicitly learn and adjust a prior that biased their perception. However, depending on the context, autistic participants showed no, normal or slower adaptation, a phenomenon that computational modeling of trial-to-trial responses helped us to associate with a higher expectation for sameness in ASD, and to dissociate from another observed robust difference in terms of response bias. These results point to atypical perceptual learning rather than altered perceptual inference per se, calling for further empirical and computational studies to refine the current predictive coding theories of ASD.

Functional and pharmacological analyses of visual habituation learning in larval zebrafish.

Habituation allows animals to learn to ignore persistent but inconsequential stimuli. Despite being the most basic form of learning, a consensus model on the underlying mechanisms has yet to emerge. To probe relevant mechanisms, we took advantage of a visual habituation paradigm in larval zebrafish, where larvae reduce their reactions to abrupt global dimming (a dark flash). We used Ca2+ imaging during repeated dark flashes and identified 12 functional classes of neurons that differ based on their rate of adaptation, stimulus response shape, and anatomical location. While most classes of neurons depressed their responses to repeated stimuli, we identified populations that did not adapt or that potentiated their response. These neurons were distributed across brain areas, consistent with a distributed learning process. Using a small-molecule screening approach, we confirmed that habituation manifests from multiple distinct molecular mechanisms, and we have implicated molecular pathways in habituation, including melatonin, oestrogen, and GABA signalling. However, by combining anatomical analyses and pharmacological manipulations with Ca2+ imaging, we failed to identify a simple relationship between pharmacology, altered activity patterns, and habituation behaviour. Collectively, our work indicates that habituation occurs via a complex and distributed plasticity processes that cannot be captured by a simple model. Therefore, untangling the mechanisms of habituation will likely require dedicated approaches aimed at sub-component mechanisms underlying this multidimensional learning process.

Association between cardiovascular diseases and dementia among various age groups: a population-based cohort study in older adults.

The link between cardiovascular (CV) risk factors or diseases and dementia is documented. There is conflicting evidence whether age moderates the association. We need to study this gap so that research and clinical initiatives target appropriate age groups. A cohort of 320,630 adult patients without dementia was built using Quebec healthcare databases (1998-2010). The CV risk factors were hypertension, diabetes and dyslipidemia, while diseases included stroke, myocardial infarction (MI), chronic heart failure (HF), and atrial fibrillation (AF). Dementia risk and CV risk factors or diseases were assessed using incidence rate ratios and Cox regression across age groups. The cohort presented by mainly female sex (67.7%) and mean age of 74.1 years. Incident rate of dementia increased with age, ranging from 4.1 to 93.5 per 1000 person-years. Diabetes, stroke, HF and AF were significantly associated with dementia risk, hazard ratios ranged from 1.08 to 3.54. The strength of association decreased in advanced age for diabetes, stroke and HF. The results suggest that prevention of diabetes, stroke, HF and AF are crucial to mitigate dementia risk. The pathophysiology of dementia in younger and older populations seems to differ, with less impact of CV risk factors in advanced age.

Intact predictive processing in autistic adults: evidence from statistical learning.

Impairment in predictive processes gained a lot of attention in recent years as an explanation for autistic symptoms. However, empirical evidence does not always underpin this framework. Thus, it is unclear what aspects of predictive processing are affected in autism spectrum disorder. In this study, we tested autistic adults on a task in which participants acquire probability-based regularities (that is, a statistical learning task). Twenty neurotypical and 22 autistic adults learned a probabilistic, temporally distributed regularity for about 40 min. Using frequentist and Bayesian methods, we found that autistic adults performed comparably to neurotypical adults, and the dynamics of learning did not differ between groups either. Thus, our study provides evidence for intact statistical learning in autistic adults. Furthermore, we discuss potential ways this result can extend the scope of the predictive processing framework, noting that atypical processing might not always mean a deficit in performance.

Neural correlates of hierarchical predictive processes in autistic adults.

Bayesian theories of autism spectrum disorders (ASD) suggest that atypical predictive mechanisms could underlie the autistic symptomatology, but little is known about their neural correlates. Twenty-six neurotypical (NT) and 26 autistic adults participated in an fMRI study where they performed an associative learning task in a volatile environment. By inverting a model of perceptual inference, we characterized the neural correlates of hierarchically structured predictions and prediction errors in ASD. Behaviorally, the predictive abilities of autistic adults were intact. Neurally, predictions were encoded hierarchically in both NT and ASD participants and biased their percepts. High-level predictions were following activity levels in a set of regions more closely in ASD than NT. Prediction errors yielded activation in shared regions in NT and ASD, but group differences were found in the anterior cingulate cortex and putamen. This study sheds light on the neural specificities of ASD that might underlie atypical predictive processing.

Determinants of motivation and adherence to a web application for health behaviour change: A qualitative study with cancer survivors.

BACKGROUND: Given the increasing number of cancer survivors, eHealth may be an effective means to improve lifestyle-related behaviours. Limited data are available on the use of eHealth by post-cancer patients. The present study aimed to analyse the contexts of use to identify the determinants of cancer survivors' adherence and motivation to use a web application offering nutrition and physical activity coaching. METHODS: Individual semi-structured interviews were conducted with cancer survivors who participated in an 8-week online program for health behaviour change. The interviews were analysed using thematic analysis. RESULTS: Fifteen patients with a mean (SD) age of 62 (4.2) years completed the interview. Four themes relating to the environment and context of use were identified: digital use, social relations, health, and digital health interventions. Participants were familiar with digital tools through their professional work. Their motivation and adherence to the program improved through social relations; notably, a supportive family in addition to a trusted prescriber, continuity in the care pathway, and an appropriate choice of design features in the digital health intervention. With cancer survivorship, individuals no longer define themselves as sick but still need support to envisage the future more serenely. CONCLUSIONS: Cancer survivorship plays a special role in people's adherence to online interventions for health behaviour change in addition to the influence of their social relations and health environment.

A multilevel investigation of sensory sensitivity and responsivity in autistic adults.

Atypical sensory processing is a core symptom of autism spectrum disorders (ASD). We aimed at better characterizing visual sensitivity and responsivity in ASD at the self-reported, behavioral and neural levels, and at describing the relationships between these levels. We refer to sensory sensitivity as the ability to detect sensory stimuli and to sensory responsivity as an affective response to sensory stimuli. Participants were 25 neurotypical and 24 autistic adults. At the self-reported level, autistic participants had higher scores of sensory sensitivity and responsivity than neurotypicals. The behavioral and neural tasks involved contrast-reversing gratings which became progressively (in)visible as their contrast or spatial frequency evolved. At the behavioral level, autistic participants had higher detection and responsivity thresholds when gratings varied in spatial frequency, but their thresholds did not differ from neurotypicals when gratings varied in contrast. At the neural level, we used fast periodic visual stimulations and electroencephalography to implicitly assess detection thresholds for contrast and spatial frequency, and did not reveal any group difference. Higher self-reported responsivity was associated with higher behavioral responsivity, more intolerance of uncertainty and anxiety, in particular in ASD. At the self-reported level, higher sensitivity was associated with more responsivity in both groups, contrary to the behavioral level where these relationships were not found. These heterogeneous results suggest that sensitivity and responsivity per se are not simply increased in ASD, but may be modulated by other factors such as environmental predictability. Multi-level approaches can shed light on the mechanisms underlying sensory issues in ASD.

Canadian Cardiovascular Society-Canadian Heart Failure Society Focused Clinical Practice Update of Patients With Differing Heart Failure Phenotypes.

A number of societies produce heart failure (HF) management guidelines, comprising official recommendations on the basis of recent research discoveries, but their applicability to specific situations encountered in daily practice might be difficult. In this clinical practice update we aim to provide responses to fundamental questions that face health care providers, like appropriate timing for the introduction and optimization of different classes of medication according to specific patient phenotypes, when second-line therapies and valvular interventions should be considered, and management of difficult clinical scenarios such as cardiorenal syndrome and frailty. A consensus-based methodology was used. Approaches to 5 different phenotypes are presented: (1) The wet HF phenotype is the easiest to manage, decongestion being performed alongside introduction of guideline-directed medical therapy (GDMT); (2) The de novo HF phenotype requires the introduction of the 4 pillars of GDMT, personalizing the order on the basis of the individuals' biological and physiological characteristics; (3) The worsening HF phenotype is a marker of poor prognosis, and therefore should motivate optimization of GDMT, start second-line therapies, and/or reevaluate goals of care/advanced HF therapies; (4) The cardiorenal phenotypes require correct volume assessment, because renal function usually improves with decongestion; and (5) The frail HF phenotype require special attention, careful drug titration, and consideration of cardiac rehabilitation programs. In conclusion, specific common HF phenotypes call for a personalized approach to improve adoption of the HF guidelines into clinical practice.