The Moncton Hospital is a Canadian hospital in Moncton, New Brunswick.The Moncton Hospital operates as a tertiary care referral hospital for New Brunswick, as well as neighbouring regions of northeastern Nova Scotia (Cumberland County) and the province of Prince Edward Island. It has specialization in neurosurgery and trauma care services.Operated by Horizon Health Network, the Moncton Hospital traces its history to 1895. The Moncton Hospital is also a teaching hospital for the Faculty of Medicine at Dalhousie University in Halifax, Nova Scotia..
Background: Immune-oncology has revolutionized cancer treatment, but some patients fail to benefit due to primary resistance and tumour-immune evasion. Extracellular vesicles (EVs) are secreted by both tumour and immune cells and mediate communication between cancer cells and the immune system. Our study used proteomic profiling of circulating EVs collected from NSCLC patients treated with immune checkpoint inhibitors (ICI) to identify predictive biomarkers of response as well as immune evasion mechanisms related to treatment resistance. Methods: EVs were isolated from plasma collected prior to ICI treatment using peptide-affinity purification and high-throughput proteomics was performed using Proximal Extension Assay. Differentially expressed EV proteins between durable (DR) and non-durable responders (NDR) were identified and evaluated using Cox proportional hazards regression, survival analysis, sex-stratified analysis, as well as pathway and network analysis. Results: Proteomics analysis identified 116 differentially expressed EV proteins between DR and NDR. NDR was characterized by enrichment of inflammatory, angiogenic, and immune-suppressive EV proteins, such as IL1RL1, TFRC, IL6ST, galectins, TNF superfamily death receptors, chemokines, and PCSK9. Pathway analysis revealed enrichment of angiogenesis, chemotaxis, ECM remodeling, and neutrophil degranulation associated with poor progression-free survival (PFS). In contrast, DR to ICI treatment was associated with EV proteins related to T- and B-cell activation and adaptive immunity. Sex-related differences in abundance and association with PFS was observed for certain EV proteins, including IL1RL1 and TFRC. A six protein EV model (IL1RL1, TFRC, ERI1, CCN5, IGFBPL1, and TNFRSF13C) demonstrated good prognostic performance for identifying NDR (AUC = 0.907) and stratified patients into three discrete risk groups. Conclusions: High-plex EV proteomics revealed biologically coherent tumour-immune signaling programs that are associated with ICI treatment resistance. Profiling circulating EVs may improve our understanding of EV-mediated immune evasion mechanisms and identify protein signatures that reflect the tumour immune microenvironment and predict response to immune checkpoint blockade.
Background:Strong leaders are essential for driving progress in pharmacy practice, yet some professionals believe that pharmacy leadership in Canada is facing a crisis. While leadership training is important for developing the next generation of leaders, there is limited understanding of the skills most valued by current health care-systems pharmacy leaders, as well as uncertainty about the effectiveness of existing training pathways. Objectives:To identify the leadership skills most valued by Canadian health care-systems pharmacy leaders and to explore perceptions of existing leadership training. Methods:As part of a mixed-methods study, virtual focus groups, based on a semistructured interview guide, were conducted with health care-systems pharmacy leaders from across Canada. Data were analyzed using reflexive thematic analysis. Results:Three focus groups (involving a total of 17 participants) were held in July 2024. The leadership skills most valued by participants were strong interpersonal skills, systems thinking, relationship-building, ability to prioritize, ability to delegate, self-awareness, and ability to coach others. Most participants had learned leadership skills on the job or through workplace-based training programs; however, these methods were considered inadequate to meet development needs. Enablers for improving leadership development included pharmacy-focused leadership training programs, mentorship, peer-support networks, guidance from professional organizations on training resources, encouragement of leadership potential in others, and provision to staff members of projects that challenge them beyond their current level of knowledge or skill. Conclusion:Improving health care-systems pharmacists' preparedness for leadership appears to require a comprehensive strategy. Suggested key approaches include increasing access to formal pharmacy-specific leadership training programs, providing mentorship, offering "stretch" opportunities, and strengthening support from professional organizations to guide development of the next generation of pharmacy leaders.
The treatment landscape for human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (mBC) in Canada is rapidly evolving. This retrospective cohort study described real-world historical treatment patterns and clinical outcomes for patients with HER2− mBC. Adults enrolled in the pan-Canadian ‘Personalize My Treatment’ cancer registry and diagnosed with stage IV HER2− mBC (01/01/2015–03/01/2022) were eligible and followed until 03/01/2023. Hormone receptor-positive (HR+)/HER2− mBC and triple-negative mBC (mTNBC) were analyzed separately and further stratified by line of therapy. Main study outcomes included treatment patterns, PIK3CA/AKT1/PTEN alteration testing/positivity rates, and overall survival (OS), all analyzed descriptively. A total of 507 patients with HER2− mBC were included (HR+/HER2− mBC: 387; mTNBC: 120; median follow-up: 54.1 months). The most common HR+/HER2− mBC treatments were cyclin‑dependent kinase 4/6 inhibitors (CDK4/6is) plus endocrine therapy (ET) in first line (1L; 55.0
Background:The scope of pharmacy practice in Canada is expanding, as are the responsibilities of health care-systems pharmacy leaders. However, there is limited knowledge of the training pathways used by current pharmacy leaders and the leadership and managerial skills they value most. Objectives:To identify key leadership skills valued by Canadian pharmacy leaders and to determine the development pathways for these skills. Methods:An electronic survey on leadership and management competencies was distributed in spring 2024 to health care-systems pharmacy leaders across Canada. Descriptive statistics, one-way analysis of variance, and linear regression were used to assess the associations between the self-reported skill deficit and sociodemographic and employment-related factors in the quantitative data. Results:A total of 141 pharmacy leaders answered some or all of the survey questions. Respondents were predominantly midcareer leaders in academic hospitals with up to 10 years' experience, many of whom had prior clinical leadership training. Respondents expressed confidence in their clinical or operational management skills and identified finance and budgeting, human resource management, and leadership as areas requiring further development. Every mean 1-point increase in the skill deficit was associated with a 2-point decrease in job satisfaction score (95% confidence interval -3.4 to -0.90, p < 0.001). Conclusions:These findings suggest the need for further leadership and management training programs. It is recommended that a national pharmacy leadership and management competency framework be developed, along with leadership certification programs offering hands-on learning opportunities.
Objective:Neonatal late-onset sepsis is associated with increased mortality and morbidity, adversely impacting long-term outcome. The objective of this study was to examine neurodevelopmental (ND) outcomes at 18 to 24 months' corrected age (CA) in infants with late-onset bacterial sepsis (LOS) and to categorize outcomes based on type of bacterial pathogen in a cohort of preterm infants born less than 29 weeks gestation in Canada. Study Design:We conducted a retrospective cohort study of all non-anomalous infants born at <29 weeks gestational age (GA) who were admitted to Canadian NICUs, from January 1, 2010, to December 31, 2017, who had an ND assessment at 18 to 24 months' CA at Canadian Neonatal Follow-Up Network clinics. The primary outcome was the composite outcome of death or ND impairment (NDI). Secondary outcomes included significant NDI, and each component of primary outcome. We compared ND outcomes among infants with Gram-positive (GP) sepsis, Gram-negative (GN) sepsis, mixed sepsis, and no sepsis using bivariate and multivariate analyses after adjusting for potential confounders. Results:Of the 3,640 infants included, 823 (22.6%) developed LOS. Of the 823 infants, 569 (69.1%) had GP sepsis, 172 (20.9%) had GN sepsis, and 82 (10%) had mixed sepsis. Infants with LOS had significantly lower birth weight, GA, younger mothers, and significantly higher rates of major neonatal morbidities compared with the no-sepsis group. In multivariable logistic regression, infants with GN sepsis and mixed sepsis had significantly higher odds of death/NDI (GN sepsis, adjusted odds ratio [aOR] = 1.80; 95% CI: 1.27, 2.54; mixed LOS, aOR = 2.38, 95% CI: 1.41, 4.01) as compared with no sepsis. Conclusion:Late-onset bacterial sepsis, particularly Gram-negative and mixed sepsis, was associated with an increased risk of adverse outcomes including death or NDI at 18 to 24 months CA in infants born <29 weeks' GA in Canada. Key Points:· Late-onset sepsis is an important risk factor for morbidity and mortality in preterm infants.. · The clinical presentations vary depending on the causative bacteria.. · There is limited data on neurodevelopmental outcomes based on type of bacterial pathogen..
