Beijing City Beijing, China

Predicting Psychotic Relapse Using Speech-Based Early Detection

OBJECTIVES: The primary goal of this study is to develop and validate a speech-based digital model to predict psychotic relapses in individuals with early psychosis. The study specifically aims to: Test the hypothesis that within-subject changes in speech coherence, connectedness, and complexity, as measured by natural language processing (NLP) tools, will accurately identify imminent relapse, up to four weeks before clinical relapse in individuals receiving care in Early Psychosis Intervention (EPI) programs. Investigate whether these speech-based relapse prediction models generalize across different languages (English and French) and are equally predictive in both males and females, addressing potential sociodemographic and linguistic influences on model performance. Explore whether combining acoustic and prosodic features with core NLP-based speech measures improves the model's sensitivity and specificity for relapse prediction. METHODS: This study will employ a longitudinal, prospective design involving 250 first-episode psychosis (FEP) patients recruited from three Early Psychosis Intervention (EPI) clinics in Ontario and Quebec. The study aims to develop and evaluate a speech-based relapse prediction model, with a particular focus on generalizing results across different languages (English and French) and genders. Participant Recruitment and Stratification: Participants: A total of 250 FEP patients, including both English- and French-speaking individuals, will be enrolled to ensure linguistic diversity. The sample will be stratified by sex to evaluate model performance across genders. Language groups: Approximately 60% of the participants will be English speakers and 40% French speakers, reflecting the population served by the EPI clinics. Gender representation: The study aims to ensure that at least 40% of participants are female to assess gender-based differences in model prediction performance. Baseline Assessments: At baseline, participants will undergo a comprehensive in-person assessment to collect a detailed profile for each patient. This will include psychiatric symptomatology using the Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale and the Personal and Social Performance (PSP) scale, and cognitive functioning. Additionally, socioeconomic variables, historical and current medication usage, substance use (e.g., cannabis), and treatment adherence will also be recorded to provide a full clinical and treatment profile for each participant. Speech Sampling and Data Collection: Monthly Speech Samples: After the baseline assessment, participants will provide monthly speech samples over the course of 24 months. These speech samples will be collected using web-based prompts that include open-ended tasks, such as picture description or recall narratives, designed to elicit spontaneous speech. Attrition and Speech Sample Estimates: Given an expected attrition rate of 35-50%, it is estimated that by the end of the study, 840-960 speech samples will be obtained from English-speaking participants and 660-870 speech samples from French-speaking participants. Speech Analysis: The collected speech samples will be analyzed using natural language processing (NLP) methods to extract key features associated with psychosis, including coherence (Measured by lexical predictability), Connectedness (Assessed using speech graph analysis) and Complexity (evaluated using the Analytic Thinking Index (ATI)). These NLP-derived speech metrics will be tracked over time to predict imminent psychotic relapses and compared across subgroups to assess the impact of language and gender on the predictive accuracy of the relapse model. Data Analysis and Generalization: The primary objective is to determine whether speech-based relapse prediction models generalize across different languages and genders. To achieve this, model performance will be evaluated across subgroups: Linguistic subgroup analysis will compare the model's performance in English- and French-speaking participants. Gender-based analysis will assess whether the predictive power of the speech-based model varies between male and female participants. This analysis will ensure that the final model can be generalized across diverse populations and adapted for use in different clinical settings.

PROPULSION SANTE: Inflammometry to Improve the Diagnostic Trajectory in Situations of Suspected Asthma in Children and Adults

BACKROUND : Asthma is one of the most prevalent chronic diseases worldwide. In Canada, it affects 11% of the population. In Quebec, an estimated 900,000 people suffer from asthma, including 300,000 children. Type 2 eosinophilic inflammation is present in 50% of asthma cases and in 95% of individuals with severe disease, who consume more healthcare resources. This type of inflammation is clinically identified through non-invasive measurements of exhaled nitric oxide (FeNO) and blood eosinophil count (BEC). Asthmatic patients with Type 2 inflammation are at higher risk of asthma attacks and appear to be at risk of accelerated lung function decline, both in adults and children. The presence of Type 2 inflammation predicts a strong response to inhaled corticosteroids (ICS). Currently, post-bronchodilator reversibility and/or bronchial hyperresponsiveness documented via spirometry are the two main approved methods for diagnosing asthma. Bronchial provocation testing is required in 80% of suspected asthma cases, but our population faces a severe lack of access to this test.The average wait time for this 1-2 hour procedure exceeds one year in our three centers. Currently, prioritization is based on the order in which requests are received, with internal referrals given priority over external ones. In Europe, FeNO is already used as a complementary diagnostic tool in primary care, while in Quebec, it is only accessible in severe asthma clinics. Type 2 eosinophilic inflammation is present in 50% of asthma cases and in 95% of severe asthma cases. This inflammation can be identified through non-invasive biomarkers, such as FeNO and blood eosinophil count. Individuals with type 2 inflammation are at higher risk for asthma attacks and are more likely to experience accelerated decline in respiratory function, both in adults and children. However, type 2 inflammation also predicts a strong response to inhaled corticosteroids (ICS).The identification of these markers represents a treatable trait. HYPOTHESIS As a prognostic procedure that identifies a treatable trait, early measurement of inflammatory biomarkers could: 1. Prioritize highly inflamed patients for bronchial provocation testing. 2. Provide personalized therapy based on the inflammation type, with evidence-based recommendations included in the medical reports. 3. Improve the management of asthmatic patients who do not respond to initial treatment, ensuring better access to specialized care. OBJECTIVES For patients ≥6 years old with suspected asthma, referred by non-pulmonologists for diagnostic testing, the study aims to use inflammometry to: 1. Reduce diagnostic delays for high-risk patients with probable asthma and exacerbation risk. 2. Enhance test result interpretation by incorporating inflammometry findings, asthma probability assessment, exacerbation risk, and expected response to anti-inflammatory therapies. 3. Alleviate waiting lists across our three centers. 4. Analyze and optimize the diagnostic pathway for suspected asthma cases in Quebec by generating real-world evidence on the clinical, economic, and environmental benefits of inflammometry. METHODOLOGY For one year, an additional respiratory therapist at each center will conduct diagnostic tests for suspected asthma (spirometry with pre/post-bronchodilator testing or methacholine challenge) requested by non-pulmonologists at the Sherbrooke University Hospital Center (CHUS), CHU Sainte-Justine, and the Montreal Children's Hospital. All patients ≥6 years old on the waiting list will be invited to a clinic visit, where a complementary assessment will be offered. This innovative approach includes: 1. FeNO measurement (exhaled air) 2. Blood eosinophil count (capillary or venous sample) 3. Questionnaires on asthma control and quality of life, completed at baseline and at 4, 8, and 12 months If spirometry is non-diagnostic, bronchial provocation will be prioritized based on inflammatory profile: 1. if ≥1 biomarker is elevated (for those ≥12 years old, FeNO ≥25 ppb or blood eosinophils ≥300 cells/µL; for those aged 6-<12 years, FeNO ≥20 ppb or eosinophils ≥300 cells/µL), the bronchial provocation test will be prioritized (<2-4 weeks). 2. If both biomarkers are low, the scheduling of the provocation test will follow the usual timelines. If spirometry or provocation confirms asthma, additional biomarker data will inform the physician about the risk of asthma attacks. OUTCOMES The primary outcome will be diagnostic delay evolution for high- vs. low-risk asthma patients, analyzed before, during, and after the project. Receiver Operating Characteristic (ROC) curves will be used to assess the diagnostic performance of inflammometry as a potential diagnostic tool, including determining thresholds that could eliminate the need for provocation test. The analyses will be completed by questionnaires evaluating user satisfaction, economic efficiency measures (cost-effectiveness, cost-utility, budget impact), and an environmental impact assessment (measured in kgCO2 emitted by inhalers used when asthma is not diagnosed). IMPACT 1/ Implementation of an evidence-based prioritization system for primary care referrals, substituting the current chronological approach, to reduce wait times for high-risk patients. 2/ Integrating biomarker results with pulmonary function test outcomes will refine their interpretation and better assess the likelihood of an asthma diagnosis, exacerbation risk, and response to anti-inflammatory treatments. 3/The resources allocated by this project will help reduce waitlists. 4/ Real-world evidence from Quebec will be used to improve the asthma diagnostic algorithm, facilitating the integration of inflammometry into asthma diagnosis in the province. This could potentially eliminate 20% of bronchial provocation tests, reducing costs with net-zero financial impact.

HYEEG Discourse in Psychosis: A Neurobehavioural Study

INTRODUCTION Schizophrenia, often associated with psychosis, is a severe mental disorder that profoundly impacts individuals, families, and society, diminishing quality of life and well-being globally. Disorganized communication-a hallmark feature of schizophrenia-is characterized by impairments in speech production, gesture-speech coordination, and motor behaviours that disrupt the ability to convey and interpret meaning in social contexts. These deficits profoundly undermine interpersonal relationships and social connectedness, creating barriers to meaningful social engagement. The impact of these challenges is particularly acute among marginalized populations, who face additional systemic obstacles such as stigma, reduced access to healthcare, and limited social support networks. The early onset of psychosis, typically during late adolescence or early adulthood, coincides with a critical developmental period marked by heightened neuroplasticity. Social preferences, communication patterns, and adaptive behaviours are formed during this period. This developmental window is particularly vulnerable to disruptions in social interactions, which can derail neurobehavioural trajectories and contribute to long-term social dysfunction. Understanding how disorganized communication emerges and persists during this critical window is essential for designing early interventions to mitigate its effects. Social disconnection-the breakdown of interpersonal connectivity and adaptability-is likely rooted in disruptions to the underlying neurobehavioural dynamics that facilitate coordinated interpersonal interactions. These dynamics include synchrony in speech, movement, and neural activity, which are crucial for effective social functioning. Despite significant advancements in mental health research, the specific neural and behavioural underpinnings of disorganized communication remain poorly understood, particularly in their relationship to broader social dysfunction in schizophrenia. Addressing these challenges requires advanced tools capable of capturing the dynamic and reciprocal processes underlying social interactions. Real-time electroencephalogram (EEG) hyperscanning offers a robust method for studying interbrain synchrony, a critical interpersonal dynamic essential for coordinated social behaviour. This technique allows for the simultaneous recording of brain activity from two individuals engaged in reciprocal sensorimotor interactions, such as cooperative imitation. By analyzing patterns of synchrony and desynchrony in interbrain activity and associated bodily dynamics, EEG hyperscanning provides a detailed framework for examining the mechanisms underlying nonverbal communication and its disruptions. This study integrates a speech elicitation protocol with standardized transcription methods and natural language processing (NLP) techniques developed by the Diverse International Scientific Consortium for Research in Thought, Language and Communication in Psychosis group. Additionally, it incorporates a validated motor imitation protocol from prior research with healthy participants. By combining EEG hyperscanning data with detailed analyses of verbal and nonverbal behaviours, the study seeks to identify disruptions in cooperative imitation and their links to speech disorganization, providing new insights into the mechanisms of disorganized communication. This research aims to elucidate the mechanisms underlying disorganized communication by linking neural synchrony to verbal coherence, motor synchrony, and other neurobehavioural responses. These findings aim to inform the development of targeted early interventions that address both the behavioural and neural dimensions of disorganized communication in individuals with psychosis. RATIONALE The frontal and temporoparietal brain regions play critical roles in selective attention, inhibitory control, and social cognition. In schizophrenia, disruptions in neural synchronization between these regions-particularly within the alpha (8-12 Hz), beta (13-30 Hz), and gamma (30-100 Hz) frequency bands-are well-documented. Impaired functional connectivity between the prefrontal cortex and temporoparietal regions may contribute to maladaptive, self-focused attention, impairing the processing and integration of external social cues. Specific dysregulations are hypothesized to underlie these deficits: alpha-band disruptions weaken attentional filtering, beta-band abnormalities impair sustained cognitive control, and gamma-band deficits disrupt the integration of social and perceptual information. These disruptions are expected to create an imbalance between internal and external processing, reducing neural coherence and phase synchronization during social exchanges. This breakdown in neural and behavioural coordination is hypothesized to manifest as neurobehavioural markers of disorganized communication-a hallmark feature of schizophrenia. SPECIFIC HYPOTHESES 1. Impairments in Inhibition-Based Imitation: Patients with schizophrenia will exhibit significant impairments in inhibition-based imitation compared to automatic imitation, as the former requires higher cognitive control. These impairments are expected to reflect deficits in executive function, particularly the ability to selectively suppress automatic responses. 2. Correlation Between Imitation and Speech Disorganization: Difficulties in inhibition-based imitation will positively correlate with the severity of speech disorganization. Speech disorganization will be measured through clinical evaluations, structured interviews, and natural language processing (NLP) analyses, highlighting shared neural mechanisms underlying executive function and social communication. 3. Reduced Interbrain Synchrony: Interbrain synchrony during interpersonal coordination, assessed using EEG hyperscanning and behavioural analysis, will be significantly reduced in patients compared to healthy controls. This reduction is expected to reflect disruptions in neural oscillations critical for effective social interaction. MULTIMODAL ANALYSES AND FUTURE DIRECTIONS This research employs multimodal exploratory analyses to investigate the relationships between interbrain synchrony, bodily activity measures, and conversational speech variables, such as verbal coherence and semantic similarity. These analyses will also explore how these measures relate to symptom severity, providing a comprehensive understanding of their interplay. By quantifying the effect sizes of these relationships, the study aims to establish foundational evidence for the development of larger-scale research. The results are expected to inform the refinement of experimental protocols, identify robust biomarkers of social dysfunction, and guide the design of targeted early interventions for individuals with psychosis.

Behavioural Development, Long-term Outcomes and Opportunities to Optimize Youth Mental Health Trajectories

We propose an accelerated longitudinal study design that allows covering a long developmental period (9 to 25 years) in a short study time (5 years follow-up). Youth and family caregivers will be recruited from various sources and followed-up annually for the first five years. Beyond this 5-year period, further follow-ups will depend on continued study funding and may be either annual or less frequent (e.g. every 3-4 years), and either interview-based or restricted to administrative data. The present study includes assessment of antecedents, opportunities and outcomes that will establish eligibility for preventive interventions; any randomised intervention studies based on this cohort will be based on the outcome for specific REB submissions in the future. Predicting the onset of DMDs using a set of readily accessible antecedents We hypothesise that youth who develop DMDs will have higher severity and frequency of antecedents compared to those who do not develop this outcome. We anticipate that a clinically meaningful prediction (i.e., with accuracy 80% or more said to be good or excellent, while less than 60% is deemed not meaningful; many existing predictors perform at 60-80% range9) of DMDs can be made with the set of readily measurable antecedents. We will estimate the strength of antecedent-outcome relationship separately in the two (help-seeking or non help-seeking) subgroups. While we expect variations in the rates of outcomes (help-seeking > non-help seeking), we hypothesise that the relationship between antecedents and DMDs will be similar across the groups with no major drop in the ability to predict outcome in any subgroup (i.e. >60% accuracy in each, below which prediction is unlikely to be of any clinical benefit59). Relationship between predictive antecedents, resilience and biobehavioural markers In the consenting subsample, we will assess if the polygenic risk of individual disorders/pathways and summary measures of brain health (age-appropriate structure, chemisty, function) differ between those who develop DMDs and those who do not. We will subsequently test if measures with highest effect size differences, if any, will improve the accuracy (discrimination index) for outcome prediction by at least 10% to assess their suitability for routine clinical implementation. Of note, we propose this study as a part of a longer program whose first phase will be for 5 years duration. We anticipate following up this cohort for a longer period in phase 2, and embedding clinical trials in the cohort in future (not described here).

A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7759065 as a Single Agent and in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

Study to Assess Efficacy Safety and Tolerability of Remibrutinib in Adult Patients With Moderate to Severe Hidradenitis Suppurativa

The total duration of the study is 76 weeks and consists of: Screening (up to 4 weeks), Treatment Period 1 (16 weeks, double-blind treatment with remibrutinib (Dose A or Dose B) or placebo, Treatment Period 2 (52 weeks, treatment with remibrutinib (Dose A or Dose B) and Safety Follow-Up (treatment-free follow-up for 4 weeks). Participants who prematurely discontinue study treatment (either during Treatment Period 1 or Treatment Period 2) are encouraged to remain in the study. Participants who do not wish to remain in the study will enter a 4-week Safety Follow-Up period.

A Phase 3 Study to Assess the Efficacy, Safety, and Tolerability of Itepekimab (Anti-IL-33 mAb) in Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps

A Study of BGB-16673 Compared to Investigator's Choice in Participants With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Both Bruton Tyrosine Kinase (BTK) and B-cell Leukemia/Lymphoma 2 Protein (BCL2) Inhibitors

Chronic lymphocytic leukemia is a type of blood cancer that affects people around the world. People with CLL suffer from enlarged lymph nodes, spleen, or liver, or have symptoms like night sweats, weight loss and fever. They have shorter life expectancy compared to healthy people. There is an urgent need for new treatment to prolong life and control disease-related symptoms. In this study, participants with relapsed/refractory (R/R) CLL who were previously exposed to a BTKi and a BCL2i will receive BGB-16673 or the investigator's choice of idelalisib plus rituximab (for CLL only) or bendamustine plus rituximab or venetoclax plus rituximab retreatment. The main purpose of this study is to compare the length of time that participants live without their CLL or SLL worsening between those participants who receive BGB-16673 versus the investigator's choice of treatment (idelalisib plus rituximab or bendamustine plus rituximab, or venetoclax plus rituximab). Approximately 250 participants will be included in this study around the world. Participants will be randomly allocated to receive either BGB-16673 or the investigator's choice of treatment.

VY7523-102: Randomized, Placebo-Controlled, Double-Blind, Multiple Ascending Dose Study in Participants with Early Alzheimer's Disease

Impact of PEG Bowel Preparation on Gut Microbiome Composition Recovery

Based on the limited literature that PEG does not significantly impact the microbiome, certain investigators ascertain that administration of PEG without any subsequent FMT would represents the gold-standard control group. On the other hand, other investigators raised their concern that perturbation of the microbiome with PEG without subsequent replacement with FMT might negatively impact immune checkpoint inhibitor efficacy. Therefore, there is an unmet need to conduct a study using the metagenomic shotgun sequencing to precisely understand the impact of bowel preparation on gut microbiome composition and on the dynamics of recovery of the gut microbiome after bowel preparation to better design microbiome-centered trials.