Spectrum of somatic mutational features of colorectal tumors in ancestrally diverse populations.

Ancestrally diverse and admixed populations, including the Hispanic/Latino/a/x/e community, are underrepresented in cancer genetic and genomic studies. Leveraging the Latino Colorectal Cancer Consortium, we analyzed whole exome sequencing data on tumor/normal pairs from 718 individuals with colorectal cancer (128 Latino, 469 non-Latino) to map somatic mutational features by ethnicity and genetic ancestry. Global proportions of African, East Asian, European, and Native American ancestries were estimated using ADMIXTURE. Associations between global genetic ancestry and somatic mutational features across genes were examined using logistic regression. TP53 , APC , and KRAS were the most recurrently mutated genes. Compared to non-Latino individuals, tumors from Latino individuals had fewer KRAS (OR=0.64, 95%CI=0.41-0.97, p=0.037) and PIK3CA mutations (OR=0.55, 95%CI=0.31-0.98, p=0.043). Genetic ancestry was associated with presence of somatic mutations in 39 genes (FDR-adjusted LRT p<0.05). Among these genes, a 10% increase in African ancestry was associated with significantly higher odds of mutation in KNCN (OR=1.34, 95%CI=1.09-1.66, p=5.74×10 -3 ) and TMEM184B (OR=1.53, 95%CI=1.10-2.12, p=0.011). Among RMGs, we found evidence of association between genetic ancestry and mutation status in CDC27 (LRT p=0.0084) and between SMAD2 mutation status and AFR ancestry (OR=1.14, 95%CI=1.00-1.30, p=0.046). Ancestry was not associated with tumor mutational burden. Individuals with above-average Native American ancestry had a lower frequency of microsatellite instable (MSI-H) vs microsatellite stable tumors (OR=0.45, 95%CI=0.21-0.99, p=0.048). Our findings provide new knowledge about the relationship between ancestral haplotypes and somatic mutational profiles that may be useful in developing precision medicine approaches and provide additional insight into genomic contributions to cancer disparities. Significance: Our data in ancestrally diverse populations adds essential information to characterize mutational features in the colorectal cancer genome. These results will help enhance equity in the development of precision medicine strategies.

An Exploration of the Interplay Between Well-being and Quality and Safety.

PURPOSE: Quality improvement and patient safety (QIPS) and clinician well-being work are interconnected and impact each other. Well-being is of increased importance in the current state of workforce shortages and high levels of burnout. The Canadian Association of Emergency Physicians (CAEP) Academic Symposium sought to understand the interplay between QIPS and clinician well-being and to provide practical recommendations to clinicians and institutions on ensuring that clinician well-being is integrated into QIPS efforts. METHODS: A team of emergency physicians with expertise in well-being and QIPS performed a literature review, drafted goals and recommendations, and presented at the CAEP Academic Symposium in 2023 for feedback. Goals and recommendations were then further refined. RESULTS: Three goals and recommendations were developed as follows: QIPS leaders and practitioners must (1) understand the potential intersection of well-being and QIPS, (2) consider a well-being lens for all QIPS work, and (3) incorporate QIPS methodology in efforts to improve clinician well-being. CONCLUSION: QIPS and clinician well-being are often closely linked. By incorporating these recommendations, QIPS strategies can enhance clinician well-being.

RéSUMé: OBJECTIF: Le travail d'amélioration de la qualité et de la sécurité des patients (QIPS) et le bien-être des cliniciens sont interreliés et ont des répercussions les uns sur les autres. Le bien-être est d'une importance croissante dans l'état actuel des pénuries de main-d'œuvre et des niveaux élevés d'épuisement professionnel. Le symposium universitaire de l'Association canadienne des médecins d'urgence (ACMU) visait à comprendre l'interaction entre le SPQI et le bien-être des cliniciens et à fournir des recommandations pratiques aux cliniciens et aux établissements pour assurer le bien-être des cliniciens. . .Le programme QIPS est intégré aux efforts du QIPS. MéTHODES: Une équipe de médecins urgentistes ayant une expertise en bien-être et QIPS a effectué une revue de la littérature, rédigé des objectifs et des recommandations, et présenté au symposium académique de l'ACMU en 2023 pour obtenir une rétroaction. Les objectifs et les recommandations ont ensuite été affinés. RéSULTATS: Trois objectifs et recommandations ont été élaborés : les dirigeants et les praticiens du SPQI doivent (1) comprendre l'intersection potentielle du bien-être et du SPQI, (2) envisager une optique du bien-être pour tous les travaux du SPQI, et (3) intégrer la méthodologie QIPS dans les efforts visant à améliorer le bien-être des cliniciens. CONCLUSIONS: Le SPQI et le bien-être des cliniciens sont souvent étroitement liés. En intégrant ces recommandations, les stratégies QIPS peuvent améliorer le bien-être des cliniciens.

Recommendations for Choosing Wisely in Pediatric Emergency Medicine: Five Opportunities to Improve Value.

Unnecessary diagnostic tests and treatments in children cared for in emergency departments (EDs) do not benefit patients, increase costs, and may result in harm. To address this low-value care, a taskforce of pediatric emergency medicine (PEM) physicians was formed to create the first PEM Choosing Wisely recommendations. Using a systematic, iterative process, the taskforce collected suggested items from an interprofessional group of 33 ED clinicians from 6 academic pediatric EDs. An initial review of 219 suggested items yielded 72 unique items. Taskforce members independently scored each item for its extent of overuse, strength of evidence, and potential for harm. The 25 highest-rated items were sent in an electronic survey to all 89 members of the American Academy of Pediatrics PEM Committee on Quality Transformation (AAP COQT) to select their top ten recommendations. The AAP COQT survey had a 63% response rate. The five most selected items were circulated to over 100 stakeholder and specialty groups (within the AAP, CW Canada, and CW USA organizations) for review, iterative feedback, and approval. The final 5 items were simultaneously published by Choosing Wisely United States and Choosing Wisely Canada on December 1, 2022. All recommendations focused on decreasing diagnostic testing related to respiratory conditions, medical clearance for psychiatric conditions, seizures, constipation, and viral respiratory tract infections. A multinational PEM taskforce developed the first Choosing Wisely recommendation list for pediatric patients in the ED setting. Future activities will include dissemination efforts and interventions to improve the quality and value of care specific to recommendations.

Use of rational subgrouping to understand variation and opportunity for improvement in time to ultrasound.

OBJECTIVE: To understand factors that contribute to variation in time to abdominal and/or pelvic ultrasound in pediatric patients in an emergency department (ED) by utilizing rational subgrouping to assess opportunity for improvement. METHODS: All abdominal and pelvic ultrasounds conducted in the Alberta Children's Hospital ED from May 2019 to April 2021 were included. Time of study order and time of study completion were obtained from the electronic health record. Statistical process control (SPC) I-charts were used to analyze the quarterly median number of minutes from ultrasound order to completion. Rational subgrouping was used to stratify the data based on sex, age, and ED shift type, and identify special cause variation between groups. Findings were used to inform local decision-making. RESULTS: Special cause variation was detected among subgroups for sex, age group, and shift type. The median time from order of an abdominal and/or pelvic ultrasound to completion of study was 155 min. Females had a median order to completion time of 178 min, while males had a completion time of 131 min. From age 0 to 3, the median time was 110 min, compared to 149 min for ages 4 to 11 and 171 min for ages 12 and older. Day shifts had a median order to completion time of 145 min, compared to 129 min for evening shifts and 269 min for night shifts. CONCLUSIONS: Longer time to study completion was observed in female patients, older patients, and during night shifts. Use of rational subgrouping supported understanding of variation among subgroups of patients evaluated with abdominal and/or pelvic ultrasound. This allowed informed decision-making regarding opportunities for improvement. Rational subgrouping is a useful methodology in planning QI initiatives as it identifies sources of variation within a nonhomogeneous population and allows for judicious decision-making in a context of limited resources.

RéSUMé: OBJECTIF: Comprendre les facteurs qui contribuent à la variation dans le temps de l'échographie abdominale et/ou pelvienne chez les patients pédiatriques dans un service d'urgence (ED) en utilisant un sous-groupe rationnel pour évaluer la possibilité d'amélioration. MéTHODES: Toutes les échographies abdominales et pelviennes effectuées à l'urgence de l'Hôpital pour enfants de l'Alberta de mai 2019 à avril 2021 ont été incluses. L'ordre et l'heure de fin de l'étude ont été obtenus à partir du dossier médical électronique. Des diagrammes en I de contrôle statistique des processus (SPC) ont été utilisés pour analyser le nombre médian trimestriel de minutes entre la commande d'échographie et l'achèvement. Un sous-groupe rationnel a été utilisé pour stratifier les données en fonction du sexe, de l'âge et du type de quart de travail aux urgences, et pour déterminer la variation des causes spéciales entre les groupes. Les conclusions ont été utilisées pour éclairer la prise de décisions à l'échelle locale. RéSULTATS: Une variation de cause spéciale a été détectée parmi les sous-groupes pour le sexe, le groupe d'âge et le type de poste. Le temps médian entre la commande d'une échographie abdominale et/ou pelvienne et la fin de l'étude était de 155 minutes. Les femelles avaient un délai médian de 178 minutes, tandis que les mâles avaient un délai de 131 minutes. De 0 à 3 ans, le temps médian était de 110 minutes, comparativement à 149 minutes pour les 4 à 11 ans et 171 minutes pour les 12 ans et plus. L'ordre médian des quarts de jour était de 145 minutes, comparativement à 129 minutes pour les quarts de soir et 269 minutes pour les quarts de nuit. CONCLUSIONS: On a observé un délai plus long avant l'achèvement de l'étude chez les patientes, les patientes âgées et pendant les quarts de nuit. L'utilisation de sous-groupes rationnels a permis de comprendre la variation entre les sous-groupes de patients évalués par échographie abdominale et/ou pelvienne. Cela a permis de prendre des décisions éclairées sur les possibilités d'amélioration. Le sous-regroupement rationnel est une méthode utile pour planifier les initiatives d'AQ, car il permet de déterminer les sources de variation au sein d'une population non homogène et de prendre des décisions judicieuses dans un contexte de ressources limitées.

Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis.

Triple-negative breast cancers (TNBC) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early-stage localized TNBC, the rate of distant recurrence remains high, and long-term survival outcomes remain poor. In a search for new therapeutic targets for this disease, we observed that elevated expression of the serine/threonine kinase calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) is highly correlated with tumor invasiveness. In validation studies, genetic disruption of CaMKK2 expression or inhibition of its activity with small molecule inhibitors disrupted spontaneous metastatic outgrowth from primary tumors in murine xenograft models of TNBC. High-grade serous ovarian cancer (HGSOC), a high-risk, poor prognosis ovarian cancer subtype, shares many features with TNBC, and CaMKK2 inhibition effectively blocked metastatic progression in a validated xenograft model of this disease. Mechanistically, CaMKK2 increased the expression of the phosphodiesterase PDE1A, which hydrolyzed cyclic guanosine monophosphate (cGMP) to decrease the cGMP-dependent activity of protein kinase G1 (PKG1). Inhibition of PKG1 resulted in decreased phosphorylation of vasodilator-stimulated phosphoprotein (VASP), which in its hypophosphorylated state binds to and regulates F-actin assembly to facilitate cell movement. Together, these findings establish a targetable CaMKK2-PDE1A-PKG1-VASP signaling pathway that controls cancer cell motility and metastasis by impacting the actin cytoskeleton. Furthermore, it identifies CaMKK2 as a potential therapeutic target that can be exploited to restrict tumor invasiveness in patients diagnosed with early-stage TNBC or localized HGSOC. SIGNIFICANCE: CaMKK2 regulates actin cytoskeletal dynamics to promote tumor invasiveness and can be inhibited to suppress metastasis of breast and ovarian cancer, indicating CaMKK2 inhibition as a therapeutic strategy to arrest disease progression.

An evaluation of satisfaction with emergency department care in children and adolescents with mental health concerns.

OBJECTIVES: We hypothesized that an association exists between satisfaction with ED mental health care delivery and patient and system characteristics. Primary: To evaluate overall satisfaction with ED mental health care delivery. Secondary: To explore aspects of ED mental health care delivery associated with general satisfaction, and patient and ED visit characteristic associated with total satisfaction scores and reported care experience themes. METHODS: We enrolled patients < 18 years of age presenting with a mental health concern between February 1, 2020 and January 31, 2021, to two pediatric EDs in Alberta, Canada. Satisfaction data were collected using the Service Satisfaction Scale, a measure of global satisfaction with mental health services. Association of general satisfaction with ED mental health care was evaluated using Pearson's correlation coefficient and variables associated with total satisfaction score was assessed using multivariable regression analyses. Inductive thematic analysis of qualitative feedback identified satisfaction and patient experience themes. RESULTS: 646 participants were enrolled. 71.2% were Caucasian and 56.3% female. Median age was 13 years (IQR 11-15). Parents/caregivers (n = 606) and adolescents (n = 40) were most satisfied with confidentiality and respect in the ED and least satisfied with how ED services helped reduce symptoms and/or problems. General satisfaction was associated with perceived amount of help received in the ED (r = 0.85) and total satisfaction with evaluation by a mental health team member (p = 0.004) and psychiatrist consultation (p = 0.05). Comments demonstrated satisfaction with ED provider attitudes and interpersonal skills and dissatisfaction with access to mental health and addictions care, wait time, and the impact of COVID-19. CONCLUSIONS: There is a need to improve ED mental health care delivery, with a focus on timely access to ED mental health providers. Access to outpatient/community-based mental health care is needed to complement care received in the ED and to provide continuity of care for youth with mental health concerns.

RéSUMé: OBJECTIFS: Nous avons émis l'hypothèse qu'il existe un lien entre la satisfaction à l'égard de la prestation de soins de santé mentale aux urgences et les caractéristiques des patients et du système. Primaire : Évaluer la satisfaction globale à l'égard de la prestation des soins de santé mentale aux urgences. Secondaire : Explorer les aspects de la prestation des soins de santé mentale aux urgences associés à la satisfaction générale, et les caractéristiques du patient et de la visite aux urgences associées aux scores de satisfaction totale et aux thèmes d'expérience de soins signalés. MéTHODES: Nous avons inscrit des patients de moins de 18 ans présentant un problème de santé mentale entre le 1er février 2020 et le 31 janvier 2021 à deux services d'urgence pédiatriques en Alberta, au Canada. Les données relatives à la satisfaction ont été recueillies à l'aide de l'échelle de satisfaction du service, une mesure de la satisfaction globale à l'égard des services de santé mentale. L'association entre la satisfaction générale et les soins de santé mentale dispensés aux urgences a été évaluée à l'aide du coefficient de corrélation de Pearson et les variables associées au score total de satisfaction ont été évaluées à l'aide d'analyses de régression multivariables. L'analyse thématique inductive des commentaires qualitatifs a permis d'identifier des thèmes liés à la satisfaction et à l'expérience des patients. RéSULTATS: 646 participants ont été inscrits. 71,2 % étaient de race blanche et 56,3 % de sexe féminin. L'âge médian était de 13 ans (IQR, 11-15). Les parents/aidants (n = 606) et les adolescents (n = 40) étaient les plus satisfaits de la confidentialité et du respect à l'urgence et les moins satisfaits de la façon dont les services d'urgence ont contribué à réduire les symptômes et/ou les problèmes. La satisfaction générale était associée à la perception de l'aide reçue aux urgences (r = 0,85) et à la satisfaction totale à l'égard de l'évaluation par un membre de l'équipe de santé mentale (p = 0,004) et de la consultation d'un psychiatre (p = 0,05). Les commentaires ont fait état d'une satisfaction à l'égard des attitudes et des compétences interpersonnelles des prestataires de soins d'urgence et d'une insatisfaction à l'égard de l'accès aux soins de santé mentale et de toxicomanie, du temps d'attente et de l'impact de l'étude COVID-19. CONCLUSIONS: Il est nécessaire d'améliorer la prestation des soins de santé mentale aux urgences, en mettant l'accent sur l'accès en temps opportun aux fournisseurs de services de santé mentale des services d'urgence. L'accès à des soins de santé mentale en consultation externe ou en milieu communautaire est nécessaire pour compléter les soins reçus aux urgences et pour assurer la continuité des soins aux jeunes ayant des problèmes de santé mentale.

Ca 2+ /Calmodulin Dependent Protein Kinase Kinase-2 (CaMKK2) promotes Protein Kinase G (PKG)-dependent actin cytoskeletal assembly to increase tumor metastasis.

Triple-negative breast cancers (TNBCs) tend to become highly invasive early during cancer development. Despite some successes in the initial treatment of patients diagnosed with early-stage localized TNBC, the rate of metastatic recurrence remains high with poor long-term survival outcomes. Here we show that elevated expression of the serine/threonine-kinase, Calcium/Calmodulin (CaM)-dependent protein kinase kinase-2 (CaMKK2), is highly correlated with tumor invasiveness. We determined that genetic disruption of CaMKK2 expression, or inhibition of its activity, disrupted spontaneous metastatic outgrowth from primary tumors in murine xenograft models of TNBC. High-grade serous ovarian cancer (HGSOC), a high-risk, poor-prognosis ovarian cancer subtype, shares many genetic features with TNBC, and importantly, CaMKK2 inhibition effectively blocked metastatic progression in a validated xenograft model of this disease. Probing the mechanistic links between CaMKK2 and metastasis we defined the elements of a new signaling pathway that impacts actin cytoskeletal dynamics in a manner which increases cell migration/invasion and metastasis. Notably, CaMKK2 increases the expression of the phosphodiesterase PDE1A which decreases the cGMP-dependent activity of protein kinase G1 (PKG1). This inhibition of PKG1 results in decreased phosphorylation of Vasodilator-Stimulated Phosphoprotein (VASP), which in its hypophosphorylated state binds to and regulates F-actin assembly to facilitate contraction/cell movement. Together, these data establish a targetable CaMKK2-PDE1A-PKG1-VASP signaling pathway that controls cancer cell motility and metastasis. Further, it credentials CaMKK2 as a therapeutic target that can be exploited in the discovery of agents for use in the neoadjuvant/adjuvant setting to restrict tumor invasiveness in patients diagnosed with early-stage TNBC or localized HGSOC.

Use of quality improvement methods to enhance implementation of a mental health care bundle in a pediatric emergency department.

OBJECTIVES: We used quality improvement methods to implement a care bundle for children presenting to a pediatric emergency department (ED) with mental health concerns. A bundle novelty was that it included an option for assessment in a partnered clinic, not in the ED, to families of children assessed as having no medical or safety concerns. The primary aim of this study was to establish successful implementation of the bundle prior to studying its impact. METHODS: The bundle included the Ask Suicide-Screening Questions to standardize risk assessment at triage, the HEADS-ED (Home, Education, Activities/Peers, Drug/Alcohol, Suicidality, Emotions/Behavior, Discharge Resources) tool for brief, scored mental health assessments, and offering an urgent appointment within 96 h for low-risk children as an alternative to ED-based assessment or as a follow-up option for patients assessed in the ED. We developed aims, driver diagrams, and outcome measures for each bundle element. Each element was introduced with small tests of change using iterative plan-do-study-act cycles. Run charts were used to determine successful completion of aims. RESULTS: Rules for special cause were met through detection of shifts in performance 5 months after bundle implementation for the Ask Suicide-Screening Questions and HEADS-ED. These bundle elements were consistently used with ≥ 80% of eligible patients, representing aim achievement. During the 6 months of providing urgent appointments, 89.3% of 159 referred families received an appointment within 96 h. CONCLUSIONS: Using quality improvement methods, we were able to successfully ensure reliable implementation of a new care bundle for pediatric patients presenting to the ED with mental health concerns and allow eligible low-risk patients to receive full assessments in a partnered clinic instead of the ED.

RéSUMé: OBJECTIFS: Nous avons utilisé des méthodes d'amélioration de la qualité pour mettre en œuvre un ensemble de soins (bundle) pour les enfants qui se présentent à un service d'urgence pédiatrique avec des problèmes de santé mentale. Une nouveauté de ce bundle était qu'il comprenait une option d'évaluation dans une clinique partenaire, et non au service des urgences, pour les familles d'enfants évalués comme n'ayant aucun problème médical ou de sécurité. L'objectif premier de cette étude était d'assurer la réussite de la mise en œuvre du bundle avant d'en étudier l'impact. MéTHODES: Le bundle comprenait le questionnaire Ask Suicide-Screening Questions pour normaliser l'évaluation du risque au triage, l'outil HEADS-ED (Home, Education, Activities/Peers, Drug/Alcohol, Suicidality, Emotions/Behavior, Discharge Resources) pour des évaluations brèves et notées de la santé mentale, et l'offre d'un rendez-vous urgent dans les 96 heures pour les enfants à faible risque comme alternative à l'évaluation à l'urgence ou comme option de suivi pour les patients évalués à l'urgence. Nous avons élaboré des objectifs, des diagrammes de pilotage et des mesures de résultats pour chaque élément du bundle. Chaque élément a été introduit avec de petits tests de changement en utilisant des cycles itératifs planifier-faire-étudier-agir. Des diagrammes de progression ont été utilisés pour déterminer la réussite des objectifs. RéSULTATS: Les règles relatives à la cause spéciale ont été respectées grâce à la détection de changements dans les performances 5 mois après la mise en œuvre de bundle pour les questions de dépistage du suicide et HEADS-ED. Ces bundles ont été systématiquement utilisés avec plus de 80 % des patients éligibles, ce qui représente un objectif atteint. Au cours des six mois pendant lesquels des rendez-vous urgents ont été proposés, 89,3 % des 159 familles référées ont obtenu un rendez-vous dans les 96 heures. CONCLUSIONS: En utilisant des méthodes d'amélioration de la qualité, nous avons réussi à assurer une mise en œuvre fiable d'un nouveau bundle de soin pour les patients pédiatriques se présentant aux urgences avec des problèmes de santé mentale et à permettre aux patients à faible risque éligibles de recevoir des évaluations complètes dans une clinique partenaire plutôt qu'aux urgences.

Clinical features at diagnosis of sickle cell disease prior to universal newborn screening in Alberta.

Objectives: Sickle cell disease (SCD) is an inherited multisystem disorder with complications starting in the first year of life. Newborn screening (NBS) can identify infants with SCD and is associated with decreased morbidity and mortality. Variation in availability of NBS in Canada, and lack of standardized screening for immigrant children, may lead to delayed diagnosis. Methods: This was a retrospective cohort study of 126 children aged 0-18 years with SCD registered with the SCD clinic at the Alberta Children's Hospital between January 2003 and January 2018, prior to province-wide universal NBS for SCD. Patient demographic information, circumstances of diagnosis, and other contextual information were collected from patient health records. Descriptive statistics were used to summarize data, with Mood's median test used to compare medians between groups. Results: Forty-three (35%) patients were born in Alberta. Patients were mostly (95.3%) of African descent. Of patients born in Alberta, 63% (26/43) were diagnosed at >12 months of age, with a median age at diagnosis of 18 months (IQR = 4-39). This was significantly older (P < 0.001) than children born in the USA or in Canadian provinces with SCD NBS programs, where the median age at diagnosis was zero months (N = 36). Of the 42% of patients born outside North America, 64% were diagnosed following an acute complication. Conclusions: This study highlights the importance of NBS for early detection and management of SCD, and the importance of screening at-risk immigrants who may not have received NBS for SCD.

A widespread length-dependent splicing dysregulation in cancer.

Dysregulation of alternative splicing is a key molecular hallmark of cancer. However, the common features and underlying mechanisms remain unclear. Here, we report an intriguing length-dependent splicing regulation in cancers. By systematically analyzing the transcriptome of thousands of cancer patients, we found that short exons are more likely to be mis-spliced and preferentially excluded in cancers. Compared to other exons, cancer-associated short exons (CASEs) are more conserved and likely to encode in-frame low-complexity peptides, with functional enrichment in GTPase regulators and cell adhesion. We developed a CASE-based panel as reliable cancer stratification markers and strong predictors for survival, which is clinically useful because the detection of short exon splicing is practical. Mechanistically, mis-splicing of CASEs is regulated by elevated transcription and alteration of certain RNA binding proteins in cancers. Our findings uncover a common feature of cancer-specific splicing dysregulation with important clinical implications in cancer diagnosis and therapies.

Adaptive stress response genes associated with breast cancer subtypes and survival outcomes reveal race-related differences.

Aggressive breast cancer variants, like triple negative and inflammatory breast cancer, contribute to disparities in survival and clinical outcomes among African American (AA) patients compared to White (W) patients. We previously identified the dominant role of anti-apoptotic protein XIAP in regulating tumor cell adaptive stress response (ASR) that promotes a hyperproliferative, drug resistant phenotype. Using The Cancer Genome Atlas (TCGA), we identified 46-88 ASR genes that are differentially expressed (2-fold-change and adjusted p-value < 0.05) depending on PAM50 breast cancer subtype. On average, 20% of all 226 ASR genes exhibited race-related differential expression. These genes were functionally relevant in cell cycle, DNA damage response, signal transduction, and regulation of cell death-related processes. Moreover, 23% of the differentially expressed ASR genes were associated with AA and/or W breast cancer patient survival. These identified genes represent potential therapeutic targets to improve breast cancer outcomes and mitigate associated health disparities.

Evaluation of parent and youth experiences in advisory groups as part of a mental healthcare clinical trial: protocol for a mixed-method study.

INTRODUCTION: Patient engagement in healthcare research is a necessity to ensure that research objectives align with priorities, outcomes and needs of the population under study, and to facilitate ease of implementation and adoption of findings. In clinical trials, there is an increasing focus on patient engagement during the planning and conduct of clinical trials due to the potential for ethical and methodological benefits. As patient engagement in clinical trials increases, there is a need to evaluate the approaches of these activities to contribute evidence on what is most appropriate and successful. The purpose of this study is to evaluate patient engagement processes and the activities of patient partners during and after a paediatric mental healthcare trial. METHODS AND ANALYSIS: Using a mixed-methods study design, we will evaluate patient partners' engagement activities across set time-points during the trial and after trial completion. In this study, the term 'patient partner' is inclusive of two groups of people with lived experience: (1) caregivers (parents, formal/informal caregivers and family), and (2) youth (aged 15-24 years). Engagement will be evaluated using the participant and project questionnaires of the Public and Patient Engagement Evaluation Tool (PPEET), followed sequentially by semi-structured interviews. Quantitative data from the PPEET questionnaire will be analysed and reported using descriptive statistics. Data from open-ended questions from the PPEET questionnaires and semi-structured interviews will be analysed using thematic analysis. ETHICS AND DISSEMINATION: Approval from Athabasca University Research Ethics Board will be obtained for this project. Findings will be disseminated at both academic and public venues whether in-person or online, and using platforms that are caregiver and youth friendly. TRIAL REGISTRATION NUMBER: NCT04902391.

An Innovative Model of Pediatric Emergency Department Mental Health Care: Protocol for a Multicenter Type 1 Effectiveness-Implementation Cluster Randomized Trial.

Over the past decade, visits to American and Canadian emergency departments (EDs) for child and youth mental health care have increased substantially.1,2 Acute mental health crises can occur as a result of a variety of concerns, including those that are life threatening (eg, suicide attempts), pose safety concerns (eg, suicidal intentions, aggressive behaviors, alcohol and other drug use), and are physically distressing to the child or youth (eg, panic attacks). ED health care providers play a vital role in assessing the safety and well-being of the child or youth and referring them to services for ongoing care.3,4 During the ED visit, assessment and care should pinpoint risks, inform treatment, and consider family needs and preferences as part of a patient-centered approach. Yet, this approach to care is not widely adopted in EDs. Most EDs do not require the use of pediatric-specific mental health tools to guide assessments or have patient-centered procedures in place to guide the care of patients with mental health emergencies.5-7 Our team believes these limitations have led to the provision of acute mental health care that can lack sufficient quality and efficiency. This study protocol describes a trial designed to evaluate if a novel mental health care bundle that was co-designed with parents and youth results in greater improvements in the well-being of children and youth 30 days after seeking ED care for mental health and/or substance misuse concerns compared with existing care protocols. We hypothesize that the bundle will positively impact child and youth well-being, while also providing cost-effective health care system benefits.