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Anna Bowers,1,2 Kristin Cleverley,1,2 Claudia Di Clemente,1 Joanna Henderson1 1Centre for Addiction and Mental Health, 2University of Toronto, Toronto, ON, Canada Abstract: There is an evident disparity between the number of youth who report experiencing problematic substance use and the number who seek treatment. To address this disparity, it is important to understand the reasons youth do and do not seek substance use treatment. Using qualitative data obtained from semistructured interviews with 31 youth aged 17–25 years presenting for treatment at a mental health hospital, the current study identifies themes in the factors that youth identify as having influenced them to seek or delay treatment. In alignment with self-determination theory, youth identified internal factors, such as wanting to better their academic, social, or financial situation, and external factors, such as familial pressure, as motivating them to seek treatment. Factors beyond those encompassed by self-determination theory were also revealed as having influenced youth decisions to seek treatment for substance abuse. These predominantly included structural factors, including satisfaction with previous treatment, accessibility of services, and availability of clinicians. These findings provide important insight for first-contact professionals and service providers looking to enhance youth motivation to seek and engage in treatment. Limitations and opportunities for future research are discussed. Keywords: substance use, mental health, youth, treatment seeking, motivation

Abstract Background Double chambered right ventricle (DCRV) is a relatively rare congenital heart disease, characterized by the abnormal division of the right ventricle into a high-pressure inlet and low-pressure outlet by anomalous muscle bundles. Extra-cardiac right-to-left shunts may present with clinical symptoms in adulthood and should be sought in patients with previous cavo-pulmonary shunt procedures. Case presentation We report a case of DCRV in a 29 year old Caucasian male presenting in adulthood with a right-to-left shunt secondary to venous collaterals, following cavopulmonary anastomosis for congenital pulmonary atresia and hypoplastic right ventricle. Conclusion Multimodality cardiac imaging using echocardiography, cardiac CT, cardiac MRI and cardiac catheterization is often required for complete characterization of complex congenital heart anomalies in adulthood.

Abstract Background Several studies have correlated elevations in cardiac biomarkers of injury post marathon with transient and reversible right ventricular (RV) systolic dysfunction as assessed by both transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR). Whether or not permanent myocardial injury occurs due to repeated marathon running in the aging population remains controversial. Objectives To assess the extent and severity of cardiac dysfunction after the completion of full marathon running in individuals greater than 50 years of age using cardiac biomarkers, TTE, cardiac computed tomography (CCT), and CMR. Methods A total of 25 healthy volunteers (21 males, 55 ± 4 years old) from the 2010 and 2011 Manitoba Full Marathons (26.2 miles) were included in the study. Cardiac biomarkers and TTE were performed one week prior to the marathon, immediately after completing the race and at one-week follow-up. CMR was performed at baseline and within 24 hours of completion of the marathon, followed by CCT within 3 months of the marathon. Results All participants demonstrated an elevated cTnT post marathon. Right atrial and ventricular volumes increased, while RV systolic function decreased significantly immediately post marathon, returning to baseline values one week later. Of the entire study population, only two individuals demonstrated late gadolinium enhancement of the subendocardium in the anterior wall of the left ventricle, with evidence of stenosis of the left anterior descending artery on CCT. Conclusions Marathon running in individuals over the age of 50 is associated with a transient, yet reversible increase in cardiac biomarkers and RV systolic dysfunction. The presence of myocardial fibrosis in older marathon athletes is infrequent, but when present, may be due to underlying occult coronary artery disease.

Background: Venezuela continues to face a humanitarian crisis, where healthcare is difficult to access and abortion is legally restricted. In response to a growing need for life-saving abortion and sexual and reproductive health (SRH) services, a digital application called Aya Contigo was co-developed with local partners to support self-managed medication abortion. We sought to evaluate this digital health tool among pregnant people seeking abortion in Venezuela., Methods: This is a mixed-methods pilot evaluation of Aya Contigo, a digital tool for pregnant people seeking abortion in Venezuela. From April to June of 2021, people in the first trimester of pregnancy were recruited via passive sampling. Once enrolled, participants accessed information and resources on the application and were supported by study team members over an encrypted chat. Following medication abortion, participants completed an online survey and a semi-structured interview. Descriptive statistics were used to evaluate the survey responses. Interviews were coded thematically and analyzed qualitatively with NVivo., Results: Forty participants seeking medication abortion in Venezuela were recruited to the study and given access to Aya Contigo. Seventeen completed the online survey (42.5%), with all participants identifying as women and a mean age of 28 (range 19-38; SD 5.55). Participants expressed confidence in Aya Contigo; 53% (9/17) felt "very supported" and the remaining 47% (8/17) felt "somewhat supported" by the app throughout the self-managed abortion process. The app was rated as highly usable, with an overall System Usability Scale score of 83.4/100. Thirteen respondents participated in a semi-structured phone interview, and qualitative analysis identified key themes relating to the experience of seeking abortion in Venezuela, the user experience with Aya Contigo, and the app's role in the existing ecosystem of abortion and contraceptive care in Venezuela., Discussion: This mixed-methods pilot study demonstrates that the Aya Contigo mobile application may support pregnant people seeking medication abortion and post-abortion contraceptive services in Venezuela. Participants valued the provision of evidence-based information, virtual accompaniment services, and locally-available sexual and reproductive health resources via the digital tool. Further research and interventions are needed to ensure that all pregnant people in Venezuela can access safe abortion and contraceptive resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Cleverley, Sergeant, Zamberlin, Medina, Tam and Gill.)

The transcriptional machinery is essential for gene expression and regulation; dysregulation of transcription can result in a range of pathologies, including neurodegeneration, cancer, developmental disorders and cardiovascular disease. A key component of RNA polymerase II-mediated transcription is the basal transcription factor IID, which is formed of the TATA box-binding protein (TBP) and 14 TBP-associated factors (TAFs), the largest of which is the TAF1 protein, encoded on the X chromosome (Xq13.1). TAF1 is dysregulated in X-linked dystonia-parkinsonism and congenital mutations in the gene are causative for neurodevelopmental phenotypes; TAF1 dysfunction is also associated with cardiac anomalies and cancer. However, how TAF1 contributes to pathology is unclear. Here, we highlight the key aspects of the TAF1 gene and protein function that may link transcriptional regulation with disorders of development, growth and adult-onset disorders of motor impairment. We highlight the need to experimentally investigate the full range of TAF1 messenger RNA variants and protein isoforms in human and mouse to aid our understanding of TAF1 biology. Furthermore, the X-linked nature of TAF1 -related diseases adds complexity to understanding phenotypes. Overall, we shed light on the aspects of TAF1 biology that may contribute to disease and areas that could be addressed for future research and targeted therapeutics., Competing Interests: We declare we have no competing interests., (© 2024 The Author(s).)

Down syndrome (DS), a prevalent cognitive disorder resulting from trisomy of human chromosome 21 (Hsa21), poses a significant global health concern. Affecting approximately 1 in 800 live births worldwide, DS is the leading genetic cause of intellectual disability and a major predisposing factor for early-onset Alzheimer's dementia. The estimated global population of individuals with DS is 6 million, with increasing prevalence due to advances in DS health care. Global efforts are dedicated to unraveling the mechanisms behind the varied clinical outcomes in DS. Recent studies on DS mouse models reveal disrupted neuronal circuits, providing insights into DS pathologies. Yet, translating these findings to humans faces challenges due to limited systematic electrophysiological analyses directly comparing human and mouse. Additionally, disparities in experimental procedures between the two species pose hurdles to successful translation. This review provides a concise overview of neuronal oscillations in human and rodent cognition. Focusing on recent DS mouse model studies, we highlight disruptions in associated brain function. We discuss various electrophysiological paradigms and suggest avenues for exploring molecular dysfunctions contributing to DS-related cognitive impairments. Deciphering neuronal oscillation intricacies holds promise for targeted therapies to alleviate cognitive disabilities in DS individuals., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The transition from pediatric to adult care poses a significant health system-level challenge impeding the delivery of quality health services for youth with chronic health conditions. In Canada and globally, the transition to adult care is regarded as a top priority in adolescent health in need of readily applicable, adaptable, and relevant national metrics to evaluate and benchmark transition success across disease populations and clinical care settings. Unfortunately, existing literature fails to account for the lack of engagement from youth and caregivers in developing indicators, and its applicability across chronic conditions, primary care involvement, and health equity considerations., Objective: Our proposed study aims to establish a consensus-driven set of quality indicators for the transition to adult care that are universally applicable across physical, developmental, and mental health conditions, clinical care settings, and health jurisdictions., Methods: Using an integrated knowledge translation (iKT) approach, a panel comprising youth, caregivers, interdisciplinary health care providers, and health system leaders will be established to collaborate with our research team to ensure that the study methodology, materials, and knowledge dissemination are suitable and reflect the perspectives of youth and their families. We will then conduct an iterative 3-round Online Modified Delphi (OMD) study (n=160) to (1) compare and contrast the perspectives of youth, caregivers, health care providers, and health system leaders on quality indicators for transition; and (2) prioritize a key set of quality indicators for transition applicable across disease populations that are the most important, useful, and feasible in the Canadian context. Using the RAND/UCLA Appropriateness Method (RAM) multistage analytic approach, data from each panel and stakeholder group will be examined separately and compared to establish a key set of indicators endorsed by both panels., Results: The study is funded by the Canadian Institutes of Health Research and Physicians Services Incorporated., Conclusions: This study will produce quality indicators to evaluate and inform action equitably to improve transition from pediatric to adult care for youth and their families in Canada., International Registered Report Identifier (irrid): PRR1-10.2196/60860., (©Alene Toulany, Dmitry Khodyakov, Sarah Mooney, Lisa Stromquist, Katherine Bailey, Claire EH Barber, Michelle Batthish, Kristin Cleverley, Gina Dimitropoulos, Jan Willem Gorter, Danijela Grahovac, Ruth Grimes, Beverly Guttman, Michèle L Hébert, Tomisin John, Lisha Lo, Dorothy Luong, Laura MacGregor, Geetha Mukerji, Jacklynn Pidduck, Vjura Senthilnathan, Rayzel Shulman, Patricia Trbovich, Sarah EP Munce. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 10.09.2024.)

Background: Youth engagement refers to the collaboration between researchers and youth to produce research. Youth engagement in health research has been shown to inform effective interventions aimed at improving health outcomes. However, limited evidence has identified promising practices to meaningfully engage youth. This synthesis aims to describe youth engagement approaches, frameworks, and barriers, as well as provide both evidence-based and youth-generated recommendations for meaningful engagement., Main Body: This review occurred in two stages: 1) a narrative review of existing literature on youth engagement and 2) a Youth Advisory Council (YAC) to review and supplement findings with their perspectives, experiences, and recommendations. The terms 'youth engagement' and 'health research' were searched in Google Scholar, PubMed, Web of Science, Scopus, and PsycINFO. Articles and non-peer reviewed research works related to youth engagement in health research were included, reviewed, and summarized. The YAC met with research team members and in separate youth-only forums to complement the narrative review with their perspectives. Types of youth engagement include participation as research participants, advisors, partners, and co-investigators. Barriers to youth engagement were organized into youth- (e.g., time commitments), researcher- (e.g., attitudes towards youth engagement), organizational- (e.g., inadequate infrastructure to support youth engagement), and system-level (e.g., systemic discrimination and exclusion from research). To enhance youth engagement, recommendations focus on preparing and supporting youth by offering flexible communication approaches, mentorship opportunities, diverse and inclusive recruitment, and ensuring youth understand the commitment and benefits involved., Conclusions: To harness the potential of youth engagement, researchers need to establish an inclusive and enabling environment that fosters collaboration, trust, and valuable contributions from youth. Future research endeavors should prioritize investigating the dynamics of power-sharing between researchers and youth, assessing the impact of youth engagement on young participants, and youth-specific evaluation frameworks., (© 2024. Crown.)

The TATA box-binding protein-associated factor 1 (TAF1) is a ubiquitously expressed protein and the largest subunit of the basal transcription factor TFIID, which plays a key role in initiation of RNA polymerase II-dependent transcription. TAF1 missense variants in human males cause X-linked intellectual disability, a neurodevelopmental disorder, and TAF1 is dysregulated in X-linked dystonia-parkinsonism, a neurodegenerative disorder. However, this field has lacked a genetic mouse model of TAF1 disease to explore its mechanism in mammals and treatments. Here, we generated and validated a conditional cre-lox allele and the first ubiquitous Taf1 knockout mouse. We discovered that Taf1 deletion in male mice was embryonically lethal, which may explain why no null variants have been identified in humans. In the brains of Taf1 heterozygous female mice, no differences were found in gross structure, overall expression and protein localisation, suggesting extreme skewed X inactivation towards the non-mutant chromosome. Nevertheless, these female mice exhibited a significant increase in weight, weight with age, and reduced movement, suggesting that a small subset of neurons was negatively impacted by Taf1 loss. Finally, this new mouse model may be a future platform for the development of TAF1 disease therapeutics., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Objectives: The purpose of this study was to examine sex-stratified independent predictors of patient-initiated discharge from an inpatient withdrawal management service and to determine whether those predictors differed by sex., Methods: This study compared people who had self-initiated versus planned discharges and used sex-stratified generalized estimating equations models to identify independent predictors of patient-initiated discharge. Predictors examined included age, ethnicity, substance of concern, tobacco use, mental health comorbidities, day of discharge, referral source, children, and social assistance funds., Results: Among females, there were 722 discharges, 116 of which were patient initiated. Among females, increasing age was associated with lower odds of patient-initiated discharge (OR = 0.97, 95% CI [0.95, 0.98]). Racialized females were nearly 2 times more likely to experience patient-initiated discharge compared with White females (OR = 1.8, 95% CI [1.09, 3.00]). Compared with weekdays, weekends were associated with over 4 times the odds of patient-initiated discharge (OR = 4.77, 95% CI [2.66, 8.56]). Having one or more mental health comorbidities was associated with lower odds of patient-initiated discharge compared with having no mental health comorbidities (OR = 0.51, 95% CI [0.32, 0.82]). Among males, there were 1,244 discharges, 185 of which were patient initiated. Among males, increasing age was associated with decreased odds of patient-initiated discharge (OR = 0.97, 95% CI [0.95, 0.98]). Compared with weekdays, weekends were associated with nearly 15 times the odds of patient-initiated discharge (OR = 14.9, 95% CI [9.11, 24.3])., Conclusions: Males and females have shared and unique predictors of patient-initiated discharge. Future studies should continue to examine the influence of sex and gender on engagement with addictions care., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article., (Copyright © 2024 International Nurses Society on Addictions.)

Introduction: Patient engagement and integrated knowledge translation (iKT) processes improve health outcomes and care experiences through meaningful partnerships in consensus-building initiatives and research. Consensus-building is essential for engaging a diverse group of experienced knowledge users in co-developing and supporting a solution where none readily exists or is less optimal. Patients and caregivers provide invaluable insights for building consensus in decision-making around healthcare, policy and research. However, despite emerging evidence, patient engagement remains sparse within consensus-building initiatives. Specifically, our research has identified a lack of opportunity for youth living with chronic health conditions and their caregivers to participate in developing consensus on indicators/benchmarks for transition into adult care. To bridge this gap and inform our consensus-building approach with youth/caregivers, this scoping review will synthesise the extent of the literature on patient and other knowledge user engagement in consensus-building healthcare initiatives., Methods and Analysis: Following the scoping review methodology from Joanna Briggs Institute, published literature will be searched in MEDLINE, EMBASE, CINAHL and PsycINFO databases from inception to July 2023. Grey literature will be hand-searched. Two independent reviewers will determine the eligibility of articles in a two-stage process, with disagreements resolved by a third reviewer. Included studies must be consensus-building studies within the healthcare context that involve patient engagement strategies. Data from eligible studies will be extracted and charted on a standardised form. Abstracted data will be analysed quantitatively and descriptively, according to specific consensus methodologies, and patient engagement models and/or strategies., Ethics and Dissemination: Ethics approval is not required for this scoping review protocol. The review process and findings will be shared with and informed by relevant knowledge users. Dissemination of findings will also include peer-reviewed publications and conference presentations. The results will offer new insights for supporting patient engagement in consensus-building healthcare initiatives., Protocol Registration: https://osf.io/beqjr., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The purpose of this study was to understand the needs of youth and young adults, current gaps around safeguarding social media, and factors affecting adoption of data-driven auto-detection or software tools., Methods: This qualitative study is the first step of a larger initiative that aims to use participatory action research and co-design principles to develop a digital tool that targets cyberbullying. Youth and young adults aged 16-21 years were recruited to participate in semistructured focus groups between March 2020 and November 2021. Thematic analysis was used to develop themes, with a member-checking process to validate the findings., Results: Six focus groups were completed with 39 participants and five themes were generated from the analysis. Participants described the mental health impacts of cyberbullying on young people, the stigma associated with it, and the need for more mental health resources. They felt that additional efforts are needed to improve the school environment, school-based interventions, and training protocols to ensure that youth feel safe reporting cyberbullying. Most participants were open to using a digital solution but raised concerns around the trustworthiness of artificial intelligence and wanted it to be co-designed with young people, integrated across platforms, informed by data-driven decisions, and transparent with users., Discussion: Youth and young adults are accepting of a low-risk digital cyberbullying solution as current interventions are not meeting their needs., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Our group developed an Integrated Care Pathway to facilitate the delivery of evidence-based care for adolescents experiencing depression called CARIBOU-2 (Care for Adolescents who Receive Information 'Bout OUtcomes, 2 nd iteration). The core pathway components are assessment, psychoeducation, psychotherapy options, medication options, caregiver support, measurement-based care team reviews and graduation. We aim to test the clinical and implementation effectiveness of the CARIBOU-2 pathway relative to treatment-as-usual (TAU) in community mental health settings., Methods and Analysis: We will use a Type 1 Hybrid Effectiveness-Implementation, Non-randomized Cluster Controlled Trial Design. Primary participants will be adolescents (planned n = 300, aged 13-18 years) with depressive symptoms, presenting to one of six community mental health agencies. All sites will begin in the TAU condition and transition to the CARIBOU-2 intervention after enrolling 25 adolescents. The primary clinical outcome is the rate of change of depressive symptoms from baseline to the 24-week endpoint using the Childhood Depression Rating Scale-Revised (CDRS-R). Generalized mixed effects modelling will be conducted to compare this outcome between intervention types. Our primary hypothesis is that there will be a greater rate of reduction in depressive symptoms in the group receiving the CARIBOU-2 intervention relative to TAU over 24 weeks as per the CDRS-R. Implementation outcomes will also be examined, including clinician fidelity to the pathway and its components, and cost-effectiveness., Ethics and Dissemination: Research ethics board approvals have been obtained. Should our results support our hypotheses, systematic implementation of the CARIBOU-2 intervention in other community mental health agencies would be indicated., (© 2024. The Author(s).)

Background: The Toronto Adolescent and Youth (TAY) Cohort Study will characterize the neurobiological trajectories of psychosis spectrum symptoms, functioning, and suicidality (i.e., suicidal thoughts and behaviors) in youth seeking mental health care. Here, we present the neuroimaging and biosample component of the protocol. We also present feasibility and quality control metrics for the baseline sample collected thus far., Methods: The current study includes youths (ages 11-24 years) who were referred to child and youth mental health services within a large tertiary care center in Toronto, Ontario, Canada, with target recruitment of 1500 participants. Participants were offered the opportunity to provide any or all of the following: 1) 1-hour magnetic resonance imaging (MRI) scan (electroencephalography if ineligible for or declined MRI), 2) blood sample for genomic and proteomic data (or saliva if blood collection was declined or not feasible) and urine sample, and 3) heart rate recording to assess respiratory sinus arrhythmia., Results: Of the first 417 participants who consented to participate between May 4, 2021, and February 2, 2023, 412 agreed to participate in the imaging and biosample protocol. Of these, 334 completed imaging, 341 provided a biosample, 338 completed respiratory sinus arrhythmia, and 316 completed all 3. Following quality control, data usability was high (MRI: T1-weighted 99%, diffusion-weighted imaging 99%, arterial spin labeling 90%, resting-state functional MRI 95%, task functional MRI 90%; electroencephalography: 83%; respiratory sinus arrhythmia: 99%)., Conclusions: The high consent rates, good completion rates, and high data usability reported here demonstrate the feasibility of collecting and using brain imaging and biosamples in a large clinical cohort of youths seeking mental health care., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Psychosis spectrum symptoms (PSSs) occur in a sizable percentage of youth and are associated with poorer cognitive performance, poorer functioning, and suicidality (i.e., suicidal thoughts and behaviors). PSSs may occur more frequently in youths already experiencing another mental illness, but the antecedents are not well known. The Toronto Adolescent and Youth (TAY) Cohort Study aims to characterize developmental trajectories in youths with mental illness and understand associations with PSSs, functioning, and suicidality., Methods: The TAY Cohort Study is a longitudinal cohort study that aims to assess 1500 youths (age 11-24 years) presenting to tertiary care. In this article, we describe the extensive diagnostic and clinical characterization of psychopathology, substance use, functioning, suicidality, and health service utilization in these youths, with follow-up every 6 months over 5 years, including early baseline data., Results: A total of 417 participants were enrolled between May 4, 2021, and February 2, 2023. Participants met diagnostic criteria for an average of 3.5 psychiatric diagnoses, most frequently anxiety and depressive disorders. Forty-nine percent of participants met a pre-established threshold for PSSs and exhibited higher rates of functional impairment, internalizing and externalizing symptoms, and suicidality than participants without PSSs., Conclusions: Initial findings from the TAY Cohort Study demonstrate the feasibility of extensive clinical phenotyping in youths who are seeking help for mental health problems. PSS prevalence is much higher than in community-based studies. Our early data support the critical need to better understand longitudinal trajectories of clinical youth cohorts in relation to psychosis risk, functioning, and suicidality., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Both cognition and educational achievement in youths are linked to psychosis risk. One major aim of the Toronto Adolescent and Youth (TAY) Cohort Study is to characterize how cognitive and educational achievement trajectories inform the course of psychosis spectrum symptoms (PSSs), functioning, and suicidality. Here, we describe the protocol for the cognitive and educational data and early baseline data., Methods: The cognitive assessment design is consistent with youth population cohort studies, including the NIH Toolbox, Rey Auditory Verbal Learning Test, Wechsler Matrix Reasoning Task, and Little Man Task. Participants complete an educational achievement questionnaire, and report cards are requested. Completion rates, descriptive data, and differences across PSS status are reported for the first participants (N = 417) ages 11 to 24 years, who were recruited between May 4, 2021, and February 2, 2023., Results: Nearly 84% of the sample completed cognitive testing, and 88.2% completed the educational questionnaire, whereas report cards were collected for only 40.3%. Modifications to workflows were implemented to improve data collection. Participants who met criteria for PSSs demonstrated lower performance than those who did not on numerous key cognitive indices (p < .05) and also had more academic/educational problems., Conclusions: Following youths longitudinally enabled trajectory mapping and prediction based on cognitive and educational performance in relation to PSSs in treatment-seeking youths. Youths with PSSs had lower cognitive performance and worse educational outcomes than youths without PSSs. Results show the feasibility of collecting data on cognitive and educational outcomes in a cohort of youths seeking treatment related to mental illness and substance use., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

While the COVID-19 pandemic has greatly exacerbated the mental health challenges of transition-aged youth (TAY) between 17 and 29 years old, it has also led to the rapid adoption of digital tools for mental health help-seeking and treatment. However, to date, there has been limited work focusing on how this shift has impacted perceptions, needs and challenges of this population in using digital tools. The current study aims to understand their perspectives on mental health help-seeking during the pandemic and emerging issues related to digital tools (e.g., digital health equity, inclusivity). A total of 16 TAY were invited from three post-secondary institutions in the Greater Toronto Area. A total of two streams of focus groups were held and participants were invited to share their perceptions, needs and experiences. Five main themes were identified: 1) Helpfulness of a centralized resource encompassing a variety of diverse mental health supports help-seeking; 2) The impact of the shift to online mental health support on the use of informal supports; 3) Digital tool affordability and availability; 4) Importance of inclusivity for digital tools; and 5) Need for additional support for mental health seeking and digital tool navigation. Future work should examine how these needs can be addressed through new and existing digital mental health help-seeking tools for TAY., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective: This systematic review examined the effectiveness of Emergency Department-based and initiated youth suicide prevention interventions for suicide attempts, suicidal ideation, hospitalization, family system functioning, and other mental health symptoms., Methods: We searched five databases for randomized controlled trial (RCT) studies that examined Emergency Department-based and initiated suicide prevention interventions among youth aged 10 to 18 years old between May 2020 to June 2022. Using Cohen's d and 95% confidence interval as our standardised metrics, we followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) and Synthesis Without Meta-Analysis in Systematic Reviews (SWiM) guidelines when synthesizing, interpreting, and reporting the findings of this review., Results: Five studies were included in this review. Findings were first synthesized according to the targeted population of the study intervention and this review's outcomes. Two interventions were effective for decreasing depressive symptoms, hospitalization recidivism, and/or increasing family empowerment. There were no interventions that reduced subsequent suicide attempts. A meta-analysis was not conducted due to the heterogeneity of the data., Conclusion: A need exists to develop and evaluate Emergency Department-based and initiated youth suicide prevention interventions that can be successfully and sustainably implemented in practice. Future research should focus on evaluating the components of interventions that effectively mitigate suicide risk among high-risk youth., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Balasa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Findings from the National College Health Assessment (2019) stated that anxiety and depression are the most prevalent diagnosed mental illnesses among Canadian postsecondary students with one-fifth of students self-reporting a lifetime diagnosis. Psychotropic medications can be an important component of a multifaceted approach to the management and treatment of mental illness and are the most commonly dispensed via community pharmacies. Community pharmacies provide an opportunity for pharmacists to have a prominent role in supporting patients' psychotropic medication management. However, there has been limited exploration of how pharmacists can address patients' psychotropic medication management needs, experiences and opportunities for improvements especially for emerging adults., Methods and Analysis: This qualitative study will incorporate Thorne's approach to interpretative description. Purposeful snowball sampling will be used to identify students (18-25 years) taking psychotropic medication(s) to manage their mental health. Participants will be interviewed one on one using a semistructured interview guide virtually. Inductive thematic analysis is underway with data analysis being iterative and reflexive using NVivo. Information provided from the interviews will be reviewed and summarised into key themes., Ethics and Dissemination: This study was approved by the University of Toronto Health Sciences Research Ethics Board (REB #43185). It is expected that there will be a very low risk for mild psychological and social harm for participants as they will have the ability to stop the interview at any time and will be aware of confidentiality. The results from this study will be used to create or adapt healthcare team services including the role of pharmacists within the healthcare ecosystem at the university and contribute to developing the next stage of research to evaluate feasibility and effectiveness of programmes at the university that help postsecondary students to manage psychotropic medication., Competing Interests: Competing interests: AM acknowledges her position as a woman currently studying at the university. There is a possibility the interviewer may encounter a participant who are known prior to the interview. If there is a participant with whom the interviewer shares a relationship, that participant will be excluded from the study to remove biases., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The economic shutdown and school closures associated with the COVID-19 pandemic have negatively influenced many young people's educational and training opportunities, leading to an increase in youth not in education, employment, or training (NEET) globally and in Canada. NEET youth have a greater vulnerability to mental health and substance use problems, compared to their counterparts who are in school and/or employed. There is limited evidence on the association between COVID-19 and NEET youth. The objectives of this exploratory study included investigating: longitudinal associations between the COVID-19 pandemic and the mental health and substance use (MHSU) of NEET youth; and MHSU among subgroups of NEET and non-NEET youth., Methods: 618 youth (14-28 years old) participated in this longitudinal, cohort study. Youth were recruited from four pre-existing studies at the Centre for Addiction and Mental Health. Data on MHSU were collected across 11 time points during the COVID-19 pandemic (April 2020-August 2022). MHSU were measured using the CoRonavIruS Health Impact Survey Youth Self-Report, the Global Appraisal of Individual Needs Short Screener, and the PTSD Checklist for DSM-5. Linear Mixed Models and Generalized Estimating Equations were used to analyze associations of NEET status and time on mental health and substance use. Exploratory analyses were conducted to investigate interactions between sociodemographic characteristics and NEET status and time., Results: At baseline, NEET youth were significantly more likely to screen positive for an internalizing disorder compared to non-NEET youth (OR = 1.92; 95%CI=[1.26-2.91] p = 0.002). No significant differences were found between youth with, and without, NEET in MHSU symptoms across the study time frame. Youth who had significantly higher odds of screening positive for an internalizing disorder included younger youth (OR = 1.06, 95%CI=[1.00-1.11]); youth who identify as Trans, non-binary or gender diverse (OR = 8.33, 95%CI=[4.17-16.17]); and those living in urban areas (OR = 1.35, 95%CI=[1.03-1.76]), compared to their counterparts. Youth who identify as White had significantly higher odds of screening positive for substance use problems (OR = 2.38, 95%CI=[1.72-3.23]) compared to racialized youth., Conclusions: Our findings indicate that sociodemographic factors such as age, gender identity, ethnicity and area of residence impacted youth MHSU symptoms over the course of the study and during the pandemic. Overall, NEET status was not consistently associated with MHSU symptoms over and above these factors. The study contributes to evidence on MHSU symptoms of NEET youth., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aim: The aim of this study is to explore nurses' experiences of seclusion or restraint use and their participation in immediate staff debriefing in inpatient mental health settings., Design: This research was conducted using a descriptive exploratory design and data were gathered through in-depth individual interviews., Methods: The experiences of nurses following seclusion or restraint use and their participation in immediate staff debriefing were explored via teleconference, using a semi-structured interview guide. Reflexive thematic analysis was used to identify prevalent themes from the data., Results: Interviews (n=10) were conducted with nurses from inpatient mental health wards in July 2020. Five themes emerged through the data analysis: (i) ensuring personal safety; (ii) grappling between the use of least-restrictive interventions and seclusion or restraint use; (iii) navigating ethical issues and personal reactions; (iv) seeking validation from colleagues and (v) attending staff debriefing based on previous experience. The themes were also analysed using Lazarus and Folkman's Transactional Model of Stress and Coping., Conclusion: Staff debriefing is a vital resource for nurses to provide and/or receive emotion- and problem-focused coping strategies. Mental health institutions should strive to establish supportive working environments and develop interventions based on the unique needs of nurses and the stressors they experience following seclusion or restraint use., Patient or Public Contribution: Nurses in both frontline and leadership roles were involved in the development and pilot test of the interview guide. The nurses who participated in the study were asked if they can be recontacted if clarification is needed during interview transcription or data analysis., (© 2023 John Wiley & Sons Ltd.)

Cathepsin B is a cysteine protease that is implicated in multiple aspects of Alzheimer's disease pathogenesis. The endogenous inhibitor of this enzyme, cystatin B (CSTB) is encoded on chromosome 21. Thus, individuals who have Down syndrome, a genetic condition caused by having an additional copy of chromosome 21, have an extra copy of an endogenous inhibitor of the enzyme. Individuals who have Down syndrome are also at significantly increased risk of developing early-onset Alzheimer's disease (EOAD). The impact of the additional copy of CSTB on Alzheimer's disease development in people who have Down syndrome is not well understood. Here we compared the biology of cathepsin B and CSTB in individuals who had Down syndrome and Alzheimer's disease, with disomic individuals who had Alzheimer's disease or were ageing healthily. We find that the activity of cathepsin B enzyme is decreased in the brain of people who had Down syndrome and Alzheimer's disease compared with disomic individuals who had Alzheimer's disease. This change occurs independently of an alteration in the abundance of the mature enzyme or the number of cathepsin B + cells. We find that the abundance of CSTB is significantly increased in the brains of individuals who have Down syndrome and Alzheimer's disease compared to disomic individuals both with and without Alzheimer's disease. In mouse and human cellular preclinical models of Down syndrome, three-copies of CSTB increases CSTB protein abundance but this is not sufficient to modulate cathepsin B activity. EOAD and Alzheimer's disease-Down syndrome share many overlapping mechanisms but differences in disease occur in individuals who have trisomy 21. Understanding this biology will ensure that people who have Down syndrome access the most appropriate Alzheimer's disease therapeutics and moreover will provide unique insight into disease pathogenesis more broadly., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Parents of children with autism spectrum disorder often report poorer sleep compared to parents of typically developing children. When parents do not obtain enough quality sleep, functioning may be compromised placing the onus of care on already stressed parents. However, improving sleep duration may not improve sleep quality and is not always feasible. This study aimed to measure sleep quality in parents of children with autism spectrum disorder, determine if stress and children's sleep are associated with sleep quality and whether resources, appraisals, and coping moderate these relationships., Materials and Methods: Multivariable regression was used to determine the effects of stress and children's sleep problems on sleep quality and test modifying effects., Results: Mean (SD) Pittsburgh Sleep Quality Index scores was 8.81 (3.76), with 77.6% of parents scoring above the clinical cut-off. Mean (SD) Children's Sleep Habits Questionnaire scores was 54.03 (8.32), with 96.3% of parents rating their child's sleep above the clinical cut-off. Children's sleep was the only significant predictor and none of the expected effect modifiers were significant., Conclusion: Children's sleep may be an important target to improve parent sleep quality but requires systematic assessment with interventional research. Implications for rehabilitationBoth parents and their 4-10-year-old children with ASD experience high levels of sleep disturbances.Clinicians can start the conversation early with parents about their children's sleep by providing them with information to increase awareness and recognize healthy sleep habits in their children.Clinicians are important in the assessment, management, and evaluation of pediatric sleep problems, which may have significant spillover effects on parents of children with ASD.There is a need for more resources and training to be available to clinicians to assess children and their parents for sleep problems, which could extend beyond the assessment of sleep and consider parent's daytime functioning and mental health.

Pediatric anxiety disorders (AD) are prevalent disorders with an impact on all aspects of a child's life and functioning. 1 Although evidence supports commonly used treatments, there are notable concerns with the research to date. 2 Heterogeneity in outcome selection, measurement, analysis, and reporting is a contributing factor to the hinderance of the translation of research into clinical practice. 3 Recognition for outcome standardization in pediatric mental health disorders is evolving and there are several initiatives of importance, including the International Consortium for Health Outcomes Measurement (ICHOM), which has developed standardized outcome sets for use in the routine clinical mental health treatment of children and adolescents. 4 Similarly, the International Alliance of Mental Health Research Funders 5 advocate for use of 1 specific outcome measurement instrument (OMI) in the youth mental health research that they fund. Development of a Core Outcome Set (COS), a minimal set of outcomes that should be measured and reported in clinical trials, has been a solution in other areas of medicine to address heterogeneity in outcome selection and measurement across trials. 6 The Core Outcomes and Measures in Pediatric Anxiety Clinical Trials (COMPACT) Initiative will develop a harmonized, evidence- and consensus-based COS that is meaningful to youth and families for use in future trials in pediatric AD., (Copyright © 2023 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this review is to provide an overview of the existing literature on psychosocial interventions aimed at addressing suicidality among adults in the context of an inpatient psychiatric admission., Introduction: For individuals admitted to a psychiatric inpatient unit, their risk of suicide in the period following discharge is significantly higher compared with the prevalence of death by suicide in the general population. During an inpatient admission, there is opportunity for supportive interventions that may lead to reduced risks of suicide. Yet, interventions that directly address suicidality have primarily been studied in outpatient settings. A broader understanding of inpatient interventions will assist clinicians in understanding key considerations when implementing suicide-related interventions in this setting., Inclusion Criteria: Studies involving adult patients (≥18 years) that describe psychosocial interventions aiming to address suicidality in the context of inpatient psychiatry will be considered. Studies that only describe pharmacological interventions will be excluded, as will studies that describe psychosocial interventions initiated in the context of an outpatient setting., Methods: We will search MEDLINE (Ovid), CINAHL (EBSCO), APA PsycINFO (EBSCOhost), the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Web of Science for studies in English and Spanish. Gray literature and materials will also be searched for using Google and websites relevant to the review topic. No date limit will be set. Two independent reviewers will screen titles and abstracts from studies that meet the inclusion criteria and review eligible studies at full text. Data will be extracted and synthesized and then presented in tabular and graphical formats accompanied by a narrative summary., Details of the Review Available at: Open Science Framework https://osf.io/5cwhx., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 JBI.)

Background: Among youth with psychiatric disorders, the transition from child to adult mental health services is a period of vulnerability to discontinuous care and service disengagement. Regular assessment of transition readiness has been identified as a core component of transition planning, contributing to successful care transitions. The Transition Readiness Assessment Questionnaire (TRAQ) 5.0 is a 20-item questionnaire that measures transition readiness in youth preparing to transition to adult care. Although the TRAQ has been validated and used across many health settings, it has not been validated in youth with primarily mental health concerns. The objective of this study was to validate the TRAQ for use among youth accessing mental health services., Methods: This study used the Longitudinal Youth in Transition Study baseline cohort, which consists of 237 clinically referred youth (aged 16-18 years) receiving outpatient mental health treatment. Psychometric evaluation of the TRAQ 5.0 included confirmatory factor analysis (CFA), assessment of internal consistency, testing convergent validity using the Dimensions of Emerging Adulthood (IDEAS) and Difficulty in Emotional Regulation (DERS) scales, criterion validity using a question on whether the participant had talked about transition with their clinician and known-group testing based on age., Results: The CFA indicated adequate fit of the five-factor TRAQ structure. The overall scale (=.86) and three of the subscales demonstrated adequate internal consistency. As hypothesized, overall TRAQ scores were higher for youth who had discussed transition and those aged 18. Small correlations were found between the overall TRAQ score and measures of developmental maturity (IDEAS) and emotional awareness (DERS); however, certain subscales did not demonstrate correlation with these constructs., Conclusions: The TRAQ 5.0 appears to be valid tool to assess the transition readiness of youth in outpatient mental health services. Additional work needs determine whether findings are similar among specific mental health conditions, including substance use disorders and psychotic disorders., (© 2022 The Authors. Child: Care, Health and Development published by John Wiley & Sons Ltd.)

The Dp(10)2Yey mouse carries a ∼2.3-Mb intra-chromosomal duplication of mouse chromosome 10 (Mmu10) that has homology to human chromosome 21, making it an essential model for aspects of Down syndrome (DS, trisomy 21). In this study, we investigated neuronal dysfunction in the Dp(10)2Yey mouse and report spatial memory impairment and anxiety-like behavior alongside altered neural activity in the medial prefrontal cortex (mPFC) and hippocampus (HPC). Specifically, Dp(10)2Yey mice showed impaired spatial alternation associated with increased sharp-wave ripple activity in mPFC during a period of memory consolidation, and reduced mobility in a novel environment accompanied by reduced theta-gamma phase-amplitude coupling in HPC. Finally, we found alterations in the number of interneuron subtypes in mPFC and HPC that may contribute to the observed phenotypes and highlight potential approaches to ameliorate the effects of human trisomy 21., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Objective: Traumatic brain injury (TBI) has been increasingly linked in population research to psychiatric problems as well as substance use and related harms, suggesting that individuals with TBI may also present more frequently to mental health and addictions (MHA) services. Little is known, however, about TBI history among MHA service users. The objectives of this review were to understand (i) the prevalence of TBI history among MHA service users; (ii) how TBI history is identified in MHA service settings; and (iii) predictors or outcomes of TBI that have been reported in MHA service users., Methods: A scoping review was conducted in accordance with PRISMA Scoping Review Extension guidelines. A search for relevant literature was conducted in MEDLINE, PsycINFO, SPORTDiscus, CINAHL, and Embase as well as various gray literature sources., Results: Twenty-eight relevant studies were identified. TBI was defined and operationalized heterogeneously between studies, and TBI history prevalence rates ranged considerably among the study samples. The included studies used varied methods to identify TBI history in MHA settings, such as clinical chart audits, single-item questions, or structured questionnaires (eg, Brain Injury Screening Questionnaire or Ohio State University TBI Identification Method). TBI history was most consistently associated with indicators of more severe substance use problems and mental health symptoms as well as increased aggression or risk to others. Studies reported less consistent findings regarding the relationship of TBI to physical health, cognitive impairment, functioning, risk to self, and type of psychiatric diagnosis., Conclusion: Screening for TBI history in MHA settings may contribute important information for risk assessment and care planning. However, to be clinically useful, assessment of TBI history will require consistent operationalization of TBI as well as use of validated screening methods., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Youth face numerous challenges in receiving coordinated and continuous mental health services, particularly as they reach the age of transition from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS). The Longitudinal Youth in Transition Study (LYiTS) follows youth prospectively as they cross this transition boundary to better understand their transition pathways and resulting symptoms and health service use outcomes. The current paper presents the baseline profile description for the LYiTS cohort and additionally examines differences in symptoms and functioning and health service utilization between youth receiving services at hospital- versus community-based CAMHS., Methods: A cross-sectional design was used. A sample of 237 16-18-year-old youth recruited from outpatient CAMHS at two hospitals and two community sites completed self-report measures at their first of four annual assessments. A latent profile analysis was conducted to identify symptomology profiles, and youth were compared on symptoms and health service use between hospital- and community-based sites., Results: Four distinct symptomology profiles were identified (subclinical, moderate internalizing, moderate externalizing, and high symptomology). Symptom profiles and functioning levels reported by youth were no different across both types of organization, although there were differences detected in health service utilization, such as type of provider seen and use of medications., Conclusions: These findings suggest that there is little difference in symptomology between youth accessing hospital versus community-based CAMHS. With growing interest in understanding the effectiveness and cost-effectiveness of different models of mental health care, these findings provide a new understanding of the clinical and service use profiles of transition-aged youth that will be explored further as this cohort is followed across the CAMHS to AMHS transition boundary.

Introduction: Mental health and/or addiction (MHA) concerns affect approximately 1.2 million children and youth in Canada, yet less than 20% receive appropriate treatment for these concerns. Youth who do not receive appropriate support may disengage from care and may experience lasting MHA issues. Families of these youth also support them in finding and accessing care. Thus, system supports are needed to help youth and their families find and equitably access appropriate care. Navigation is an innovation in MHA care, providing patient-centred support and care planning that helps individuals and families overcome barriers to care. Despite the increasing availability of navigation services for youth with MHA concerns, practices and models vary, and no single source has synthesised evidence regarding approaches and outcomes for this population into comprehensive standards., Methods and Analysis: The proposed research will bring together evidence in youth MHA navigation, to establish this important system support as a factor that can enhance the integration and continuity of care for these youth. Our team, which includes researchers, administrators, clinical leads, an MHA navigator and youth and caregivers with lived experience, will be involved in all project stages. Realist Review and Synthesis methodology will be used, the stages of which include: defining scope, searching for evidence, appraising studies and extracting data, synthesising evidence and developing conclusions, and disseminating findings., Ethics and Dissemination: Ethics approval is not required, as the study involves review of existing data. Dissemination plans include scientific publications and conferences and online products for stakeholders and the general public., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Youth accessing mental health care often experience a disruption in care as they attempt to transition between child and adolescent mental health services (CAMHS) and adult mental health services (AMHS). Few studies have evaluated interventions seeking to improve the experience and outcomes of CAMHS-AMHS transitions, in part due to lack of consensus on what constitutes best practices in intervention success. As such, the aim of this study was to engage patients, caregivers, and clinicians to prioritize core components of successful CAMHS-AMHS transitions which can be used in the design or evaluation of transition interventions. As such, a Delphi study was conducted to determine core components of successful CAMHS-AMHS transitions. Guided by the principles of patient-oriented research, three balanced expert panels consisting of youth, caregivers, and clinicians ranked and provided feedback on the importance and feasibility of core components of CAMHS-AMHS transitions. Components endorsed as feasible or important with ≥ 70% agreement from any panel moved to the next round. As a result, a list of 26 core components of CAMHS-AMHS transitions has been refined which can be used in the design, implementation, or evaluation of interventions intended to improve transition experiences and outcomes for youth in mental health care. Youth and families were engaged in an expert advisory role throughout the research process, contributing their important perspectives to the design and implementation of this study, as well as interpretation of the findings., (© 2021. The Author(s).)

Background: Youth mental health appears to have been negatively impacted by the COVID-19 pandemic. The impact on substance use is less clear, as is the impact on subgroups of youth, including those with pre-existing mental health or substance use challenges., Objective: This hypothesis-generating study examines the longitudinal evolution of youth mental health and substance use from before the COVID-19 pandemic to over one year into the pandemic among youth with pre-existing mental health or substance use challenges., Method: A total of 168 youth aged 14-24 participated. Participants provided sociodemographic data, as well as internalizing disorder, externalizing disorder, and substance use data prior to the pandemic's onset, then every two months between April 2020-2021. Linear mixed models and Generalized Estimating Equations were used to analyze the effect of time on mental health and substance use. Exploratory analyses were conducted to examine interactions with sociodemographic and clinical characteristics., Results: There was no change in internalizing or externalizing disorder scores from prior to the pandemic to any point throughout the first year of the pandemic. Substance use scores during the pandemic declined compared to pre-pandemic scores. Exploratory analyses suggest that students appear to have experienced more mental health repercussions than non-students; other sociodemographic and clinical characteristics did not appear to be associated with mental health or substance use trajectories., Conclusions: While mental health remained stable and substance use declined from before the COVID-19 pandemic to during the pandemic among youth with pre-existing mental health challenges, some youth experienced greater challenges than others. Longitudinal monitoring among various population subgroups is crucial to identifying higher risk populations. This information is needed to provide empirical evidence to inform future research directions.

Background: The association of diet quality with depression among the pediatric age group has been inconsistent. This may be due, in part, to varying dietary assessment methods. The current study sought to examine this association, and its reliability, using four dietary measures previously studied in children and adolescents., Methods: Dietary habits among 139 children and adolescents (10-18 years, 66% female) with major depressive disorder [MDD ( n  = 77)], non-MDD psychiatric conditions (PSYCH; n  = 31), or without psychiatric illness (healthy controls [HC]; n  = 31) were examined. Using self-reported dietary intake, diet quality was characterized using the Youth Healthy Eating Index (YHEI), Dietary Questionnaire (DQ), Health Behaviour of Teenagers (HBT), and the Healthy Eating Habits Scale (HEHS). Multivariate Analysis of Covariances examined the association between depression status and dietary habits across measures controlling for participant age., Results: The multivariate effect was significant by diet measures, F (16, 256) = 1.9, p  = .02, partial η 2  = 0.12, with significant differences across groups on consumption of healthy dietary practices and minimal variability across measures. In subgroup analyses, MDD children had decreased consumption of healthy foods compared with PSYCH and HC children on three out of four measures. There was no difference in consumption of unhealthy foods across diagnostic groups., Limitations: Cross-sectional design., Conclusions: Children with MDD consume fewer healthy foods than non-MDD children, with little variation by dietary measure. Research examining the directionality of this association and specific dietary deficits among MDD youth is needed to elucidate potential preventative targets for intervention.

Individuals who have Down syndrome (DS) frequently develop early onset Alzheimer's disease (AD), a neurodegenerative condition caused by the buildup of aggregated amyloid-β (Aβ) and tau proteins in the brain. Aβ is produced by amyloid precursor protein ( APP ), a gene located on chromosome 21. People who have DS have three copies of chromosome 21 and thus also an additional copy of APP ; this genetic change drives the early development of AD in these individuals. Here we use a combination of next-generation mouse models of DS (Tc1, Dp3Tyb, Dp(10)2Yey and Dp(17)3Yey) and a knockin mouse model of Aβ accumulation ( App NL-F ) to determine how chromosome 21 genes, other than APP , modulate APP/Aβ in the brain when in three copies. Using both male and female mice, we demonstrate that three copies of other chromosome 21 genes are sufficient to partially ameliorate Aβ accumulation in the brain. We go on to identify a subregion of chromosome 21 that contains the gene(s) causing this decrease in Aβ accumulation and investigate the role of two lead candidate genes, Dyrk1a and Bace2 Thus, an additional copy of chromosome 21 genes, other than APP , can modulate APP/Aβ in the brain under physiological conditions. This work provides critical mechanistic insight into the development of disease and an explanation for the typically later age of onset of dementia in people who have AD in DS, compared with those who have familial AD caused by triplication of APP SIGNIFICANCE STATEMENT Trisomy of chromosome 21 is a commonly occurring genetic risk factor for early-onset Alzheimer's disease (AD), which has been previously attributed to people with Down syndrome having three copies of the amyloid precursor protein ( APP ) gene, which is encoded on chromosome 21. However, we have shown that an extra copy of other chromosome 21 genes modifies AD-like phenotypes independently of APP copy number (Wiseman et al., 2018; Tosh et al., 2021). Here, we use a mapping approach to narrow down the genetic cause of the modulation of pathology, demonstrating that gene(s) on chromosome 21 decrease Aβ accumulation in the brain, independently of alterations to full-length APP or C-terminal fragment abundance and that just 38 genes are sufficient to cause this., (Copyright © 2022 the authors.)

Background and Objective: Transition from pediatric to adult care is associated with adverse health outcomes for many adolescents with chronic illness. We identified quality indicators for transition to adult care that are broadly applicable across chronic illnesses and health systems., Methods: Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature were searched, covering earliest available date to July 2021. The Gray Matters framework was used to search gray literature. Two independent reviewers screened articles by title and abstract, followed by full-text review. Disagreements were resolved by a third reviewer. Studies were included that identified quality indicators developed via consensus-building methods. Indicators were organized into a framework categorized by illness specificity, level of care, Donabedian model, and Institute of Medicine quality domain. Appraisal of Guidelines for Research and Evaluation tool was used for critical appraisal., Results: The search identified 4581 articles, of which 321 underwent full-text review. Eight peer-reviewed studies and 1 clinical guideline were included, identifying 169 quality indicators for transition. Of these, 56% were illness specific, 43% were at the patient level of care, 44% related to transition processes, and 51% were patient centered and 0% equity focused. Common indicator themes included education (12%), continuity of care (8%), satisfaction (8%), and self-management/self-efficacy (7%). The study was limited by quality indicators developed through consensus-building methodology., Conclusions: Although most quality indicators for transition were patient-centered outcomes, few were informed by youth and parents/caregivers, and none focused on equity. Further work is needed to prioritize quality indicators across chronic illness populations while engaging youth and parents/caregivers in the process.

Background: There are growing calls to engage service users in research about issues relevant to them. Youth and family members can make meaningful contributions to research projects, improving quality and relevance. However, more information is needed on the contributions that youth and family members can make to various study designs., Objective: This paper describes the contributions that youth and family members have made to a multi-site pragmatic randomized-controlled trial, YouthCan IMPACT, and the way project-based engagement learnings accelerated change at the institutional level and beyond., Results: Youth and family members were full members of the project team, including the project's core governance and working groups. They contributed to project leadership, as funding co-applicants and as equal members of the governance team. They were also engaged in study design. Youth defined the primary outcome measure and contributed to decisions on all secondary measures. The service pathway was co-designed with youth and family members; for example, they guided the inclusion of peer support and a family member intervention as core service components. Study implementation contributions included ensuring a youth- and family-friendly research process and training research staff on working with youth and family members. Knowledge translation activities have included youth and family members as co-presenters and manuscript co-authors. The learnings from this trial have been leveraged to expand youth and family engagement at the institution and beyond., Conclusions: Youth and family members make substantial contributions to complex research projects, including randomized-controlled trials, thereby improving project design, study implementation, associated interventions, and knowledge translation., (© 2021 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

The post-discharge period is an extremely vulnerable period for patients, particularly for those discharged from inpatient children and adolescent mental health services (CAMHS). Poor discharge practices and discontinuity of care can put children and youth at heightened risk for readmission, among other adverse outcomes. However, there is limited understanding of the structure and effectiveness of interventions to facilitate discharges from CAMHS. As such, a scoping review was conducted to identify the literature on discharge interventions. This scoping review aimed to describe key components, designs, and outcomes of existing discharge interventions from CAMHS. Nineteen documents were included in the final review. Discharge interventions were extracted and summarized for pre-discharge, post-discharge, and bridging elements. Results of this scoping review found that intervention elements included aspects of risk assessment, individualized care, discharge preparation, community linkage, psychoeducation, and follow-up support. Reported outcomes of discharge interventions were also extracted and included positive patient and caregiver satisfaction, improved patient health outcomes, and increased cost effectiveness. Literature on discharge interventions from inpatient CAMHS, while variable in structure, consistently underscore the role of such interventions in minimizing patient and family vulnerability post-discharge. However, findings are limited by inadequate reporting and heterogeneity across studies. There is a need for further research into the design, implementation, and evaluation of interventions to support successful discharges from inpatient child and adolescent mental health care., (© 2020. The Author(s).)

Individuals who have Down syndrome (trisomy 21) are at greatly increased risk of developing Alzheimer's disease, characterised by the accumulation in the brain of amyloid-β plaques. Amyloid-β is a product of the processing of the amyloid precursor protein, encoded by the APP gene on chromosome 21. In Down syndrome the first site of amyloid-β accumulation is within endosomes, and changes to endosome biology occur early in Alzheimer's disease. Here, we determine if primary mouse embryonic fibroblasts isolated from a mouse model of Down syndrome can be used to study endosome and APP cell biology. We report that in this cellular model, endosome number, size and APP processing are not altered, likely because APP is not dosage sensitive in the model, despite three copies of App., Competing Interests: F.K.W. has undertaken consultancy for Elkington and Fife Patent Lawyers unrelated to the work in the manuscript and is also a PLoS ONE Academic Editor. This does not alter our adherence to PLoS ONE policies on sharing data or materials

Introduction: An important consideration for determining the severity of mental health symptoms is their impact on youth's daily lives. Those wishing to assess 'life impact' face several challenges: First, various measurement instruments are available, including of global functioning, health-related quality of life and well-being. Existing reviews have tended to focus on one of these domains; consequently, a comprehensive overview is lacking. Second, the extent to which such instruments truly capture distinct concepts is unclear. Third, many available scales conflate symptoms and their impact, thus undermining much needed analyses of associations between the two., Methods and Analysis: A scoping umbrella review will examine existing reviews of life impact measures for use with children and youth aged 6-24 years in the context of mental health and well-being research. We will systematically search six bibliographic databases (MEDLINE, Embase, APA PsycINFO, CINAHL, Web of Science, and the COSMIN database of systematic reviews of outcome measurement instruments), and conduct systematic record screening, data extraction and charting based on methodological guidance by the Joanna Briggs Institute. Data synthesis will involve the tabulation of scale characteristics, feasibility and measurement properties, and the use of summary statistics to synthesise how these instruments operationalise life impact. The protocol was registered prospectively with the Open Science Framework (osf.io/ers48)., Ethics and Dissemination: This study will provide a comprehensive road map for researchers and clinicians seeking to assess life impact in youth mental health, providing guidance in navigating available measurement options. We will seek to publish the findings in a leading peer-reviewed journal in the field. Formal research ethics approval will not be required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pediatric nurses care for some of the most vulnerable patients in our healthcare system and are vulnerable to the impact of the stress of their work on their well-being. Burnout is a potential response to chronic interpersonal stressors and a negative work outcome linked to personal and professional consequences. A thorough understanding of the experience and factors associated with burnout in this population is an important part of developing interventions to mitigate or prevent this workplace outcome. Therefore, our study objectives were to: (1) explain and expand our understanding of pediatric critical care nurses experience of burnout in relation to their work environment and work engagement; (2) provide recommendations for nursing administrators to improve nurses' work environment, work attitudes, and work outcomes., Methods: A convenience sample of pediatric critical care nurses from a large pediatric quaternary care hospital in Ontario, Canada were invited to participate in this second phase of a sequential explanatory mixed-methods study. Semi-structured interviews were conducted, with and main themes and subthemes distilled through the method of interpretive description., Results: A total of 18 PICU/CCCU/NICU nurses participated. Derived themes included the experience and identification of burnout, including its prevalence and elusiveness. Their experiences of quality of work-life included themes such as compensation, emotional support at work, respect, their professional identity, and spill over into home life. They discussed components of work engagement, including the work itself, investment into their growth and development, and the meaning of their work. The self-care subthemes included the importance of preparation and recovery, and the use of physical and mental separation as a preservation strategy. The participants' recommendations for strategies to mitigate burnout were also summarized., Conclusion: Burnout is a complex and regularly occurring experience for pediatric critical care nurses. Although the experience may be difficult to self-identify, the impacts on the individuals are profound. Further research and organizational support are needed to test practical and evidence-based interventions to improve the well-being of this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Buckley, Berta, Cleverley and Widger.)

Background: There are no guidelines available for what assessment tools to use in a patient's self-completed online geriatric assessment (GA) with management recommendations. Therefore, we used a modified Delphi approach with Canadian expert clinicians to develop a consensus online GA plus recommendations tool., Methods: The panel consisted of experts in geriatrics, oncology, nursing, and pharmacy. Experts were asked to rate the importance and feasibility of assessments and interventions to be included in an online GA for patients. The items included in the first round were based on guidelines for in-person GA and literature review. The first two rounds were conducted using an online survey. A virtual 2 h meeting was held to discuss the items where no consensus was reached and then voted on in the final round., Results: 34 experts were invited, and 32 agreed to participate. In round 1, there were 85 items; in round 2, 50 items; and in round 3, 25 items. The final tool consists of fall history, assistive device use, weight loss, medication review, need help taking medication, social supports, depressive symptoms, self-reported vision and hearing, and current smoking status and alcohol use., Conclusion: This first multidisciplinary consensus on online GA will benefit research and clinical care for older adults with cancer.

Issues: Early discharges, also known as 'against medical advice' discharges, frequently occur in inpatient withdrawal management settings and can result in negative outcomes for patients. The purpose of this scoping review is to identify what is known about predictors of and reasons for the early discharge among adults accessing inpatient withdrawal management settings., Approach: MEDLINE, CINAHL, PsycINFO, ASSIA and EMBASE were searched, resulting in 2587 articles for screening. Title and abstract screening and full-text review were completed by two independent reviewers. Results were synthesised in quantitative and qualitative formats., Key Findings: Sixty-two studies were included in this scoping review. All studies focused on predictors of early discharge, except one which only described reasons for the early discharge. Forty-eight percent of studies involved retrospective review of health records data. The most frequently examined variables were demographics. Variables related to the treatment setting, such as referral source and treatment received, were examined less frequently but were more consistently associated with early discharge compared to demographics. Only six studies described patient reasons for the early discharge, which were retrieved via clinical documentation. The most common reasons for early discharge were dissatisfaction with treatment and family issues., Implications and Conclusions: Most demographic variables do not consistently predict early discharge, and reasons for early discharge are not well understood. Future studies should focus on the predictive value of non-patient-level variables, or conduct analyses to account for predictors of early discharge among different subgroups of people (e.g. by gender or ethnicity). Qualitative research exploring patient perspectives is needed., (© 2021 Australasian Professional Society on Alcohol and other Drugs.)