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Costimulatory receptors such as glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) play key roles in regulating the effector functions of T cells. In human clinical trials, however, GITR agonist antibodies have shown limited therapeutic effect, which may be due to suboptimal receptor clustering-mediated signaling. To overcome this potential limitation, a rational protein engineering approach is needed to optimize GITR agonist-based immunotherapies. Here we show a bispecific molecule consisting of an anti-PD-1 antibody fused with a multimeric GITR ligand (GITR-L) that induces PD-1-dependent and FcγR-independent GITR clustering, resulting in enhanced activation, proliferation and memory differentiation of primed antigen-specific GITR+PD-1+ T cells. The anti-PD-1-GITR-L bispecific is a PD-1-directed GITR-L construct that demonstrated dose-dependent, immunologically driven tumor growth inhibition in syngeneic, genetically engineered and xenograft humanized mouse tumor models, with a dose-dependent correlation between target saturation and Ki67 and TIGIT upregulation on memory T cells. Anti-PD-1-GITR-L thus represents a bispecific approach to directing GITR agonism for cancer immunotherapy.

Background: The application of self-determination theory in explaining student achievement has been well-established in various contexts. However, its application to medical education, particularly in interprofessional education (IPE) remains underexplored. Understanding how students' motivation plays a role in students' engagement and achievement is essential to optimize efforts to improve learning and instruction. Objective: This two-stage study aims to contextualize the SDT framework to IPE through the adaptation of the Basic Psychological Need Satisfaction to IPE (Study 1) and to demonstrate how SDT can be applied in IPE by examining a model of SDT constructs (Study 2) in predicting outcomes (behavioral engagement, team effectiveness, collective dedication, goal achievement). Design: In Study 1 (n=996), we adapted and validated BPNS-IPE using confirmatory factor analysis and multiple linear regression using data from 996 IPE students (Chinese Medicine, Medicine, Nursing, and Pharmacy). In Study 2 (n=271), we implemented an IPE program where we integrated SDT approaches and examined the relationship of SDT constructs with IPE outcomes using multiple linear regression. Results: Our data supported the three-factor structure (autonomy, competence, and relatedness) of BPNS-IPE, meeting the required model fit. Autonomy predicted team effectiveness (F=51.290, p<.05, R²=.580); competence predicted behavioral engagement (F=55.181, p<.05, R²=.598); while relatedness predicted significantly four IPE outcomes: behavioral engagement (F=55.181, p<.01, R²=.598), team effectiveness (F=51.290, p<.01, R²=.580), collective dedication (F=49.858, p<.01, R²=.573), goal achievement (F=68.713, p<.01, R²=.649). Conclusions: The SDT motivational framework can be adapted and applied in the IPE context to understand and enhance student motivation in medical education. Potential studies with the use of the scale are provided to guide researchers. [ABSTRACT FROM AUTHOR]

Background Best practice recommendations support the implementation of perioperative geriatric care models that tailor to the specific needs of older adults undergoing surgery. The objective of this study was to describe the current proactive perioperative geriatric programs and pathways in Canadian hospitals. Methods A survey of geriatricians, surgeons, and anesthesiologists practicing in Canada combined with phone interviews of a subset of participants were used to determine characteristics of perioperative geriatric pathways or programs including eligibility, team composition, and intervention elements. Results Analysis of 132 survey respondents and 24 interviews showed 47% (40 out of 85) of hospitals described had elements of a perioperative geriatrics program and 20% had two or more elements. Eleven themes emerged including: how perioperative geriatric care programs built geriatric competencies in other health-care providers; geriatric assessment identified risks not captured in standard perioperative risk assessment; perceived value for patients and the health-care team; delirium prevention was addressed; most programs were reactive; most programs were informal; virtual care may be used to meet demand; successful implementation required system buy-in with collaboration across subspecialties; mechanisms to drive improvement were accountability and data evaluation; few clinicians with geriatric expertise; and other priorities limited program implementation. Conclusions There were few hospitals in Canada with perioperative geriatric care models and even fewer with elements spanning the entire perioperative pathway. Strengths, weaknesses, opportunities, and threats to inform the implementation and sustainability of perioperative geriatric care in the Canadian context were identified in this national environmental scan. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic has had deleterious impacts on pediatric patients and families, as well as the healthcare providers who have attended to their care needs. Methods: In this qualitative study, children with a cardiac transplant, as well as their families and healthcare providers were interviewed to explore the impact of the COVID‐19 pandemic on pediatric care, as well as on patients' and their families' daily lives. Participants were recruited from a children's hospital in western Canada. Fifteen caregiving parents of transplanted children, 2 young patients, and 8 healthcare providers participated in interviews. Results: Findings highlighted how families and their healthcare providers experienced pandemic‐related shifts. Themes highlighted experiences, which entailed (1) initially hearing about the COVID‐19 pandemic; (2) learning about their new reality; (3) adjusting to the pandemic; (4) adjusting to shifts in pediatric services; (5) evolving a view on the future, and (6) offering recommendations for cardiac care in a pandemic. Conclusions: Study implications emphasize the need to critically reflect on, and advance, methods of helping young patients and their families in pandemic circumstances, and supporting healthcare providers. [ABSTRACT FROM AUTHOR]