Engaging with peers to integrate community care: Knowledge synthesis and conceptual map.

CONTEXT: Engaging with peers is gaining increasing interest from healthcare systems in numerous countries. Peers are people who offer support by drawing on lived experiences of significant challenges or 'insider' knowledge of communities. Growing evidence suggests that peers can serve as a bridge between underserved communities and care providers across sectors, through their ability to build trust and relationships. Peer support is thus seen as an innovative way to address core issues of formal healthcare, particularly fragmentation of care and health inequalities. The wide body of approaches, goals and models of peer support speaks volumes of such interest. Navigating the various labels used to name peers, however, can be daunting. Similar terms often hide critical differences. OBJECTIVES/BACKGROUND: This article seeks to disentangle the conceptual multiplicity of peer support, presenting a conceptual map based on a 3-year knowledge synthesis project involving peers and programme stakeholders in Canada, and international scientific and grey literature. SYNTHESIS/MAIN RESULTS: The map introduces six key questions to navigate and situate peer support approaches according to peers' roles, pathways and settings of practice, regardless of the terms used to label them. As a tool, it offers a broad overview of the different ways peers contribute to integrating health and community care. DISCUSSION: We conclude by discussing the map's potential and limitations to establish a common language and bridge models, in support of knowledge exchange among practitioners, policymakers and researchers. PATIENT OR PUBLIC CONTRIBUTION: Our team includes one experienced peer support worker. She contributed to the design of the conceptual map and the production of the manuscript. More than 10 peers working across Canada were also involved during research meetings to validate and refine the conceptual map.

Molecular pathology for cholangiocarcinoma: a review of actionable genetic targets and their relevance to adjuvant & neoadjuvant therapy, staging, follow-up, and determination of minimal residual disease.

Cholangiocarcinoma (CCA) represents a group of epithelial cell tumors classified based on their anatomic location along the biliary tree. This rare malignancy is often diagnosed at an advanced stage and deemed unresectable. Even for those patients who are surgical candidates, recurrence rates are high and survival rates low. The mainstay of therapy for advanced CCA remains cisplatin plus gemcitabine, with a median overall survival (mOS) under 12 months, although the TOPAZ-1 trial showed a survival benefit with the addition of programmed cell death ligand 1 (PD-L1) blockade. In recent years, molecular profiling has revealed a wealth of potentially targetable genetic alterations, including fibroblast growth factor receptor (FGFR) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, human epidermal growth factor receptor 2 (HER2) amplification and overexpression, and microsatellite instability (MSI). These discoveries have prompted numerous clinical trials employing drugs against these specific genetic changes. The foundation laid by early clinical studies and the landscape of ongoing trials are both summarized here. While the role of adjuvant therapy has yet to be defined in this disease, we emphasize the importance of employing targeted therapies in trials in the adjuvant and neoadjuvant spaces and discuss ways to overcome challenges due to low incidence of targetable mutations. Personalized medicine for this disease promises significant clinical benefit to patients, but further investigation is needed.

How compassionate communities are implemented and evaluated in practice: a scoping review.

BACKGROUND: Compassionate communities are rooted in a health promotion approach to palliative care, aiming to support solidarity among community members at the end of life. Hundreds of compassionate communities have been developed internationally in recent years. However, it remains unknown how their implementation on the ground aligns with core strategies of health promotion. The aim of this review is to describe the practical implementation and evaluation of compassionate communities. METHODS: We undertook a scoping review of the empirical peer-reviewed literature on compassionate communities. Bibliographic searches in five databases were developed with information specialists. We included studies in English describing health promotion activities applied to end-of-life and palliative care. Qualitative analysis used inductive and deductive strategies based on existing frameworks for categorization of health promotion activities, barriers and facilitators for implementation and evaluation measures. A participatory research approach with community partners was used to design the review and interpret its findings. RESULTS: Sixty-three articles were included for analysis. 74.6% were published after 2011. Health services organizations and providers are most often engaged as compassionate community leaders, with community members mainly engaged as target users. Adaptation to local culture and social context is the most frequently reported barrier for implementation, with support and external factors mostly reported as facilitators. Early stages of compassionate community development are rarely reported in the literature (stakeholder mobilization, needs assessment, priority-setting). Health promotion strategies tend to focus on the development of personal skills, mainly through the use of education and awareness programs. Few activities focused on strengthening community action and building healthy public policies. Evaluation was reported in 30% of articles, 88% of evaluation being analyzed at the individual level, as opposed to community processes and outcomes. CONCLUSIONS: The empirical literature on compassionate communities demonstrates a wide variety of health promotion practices. Much international experience has been developed in education and awareness programs on death and dying. Health promotion strategies based on community strengthening and policies need to be consolidated. Future research should pay attention to community-led initiatives and evaluations that may not be currently reported in the peer-review literature.

Human epidermal growth factor receptor 2 expression in head and neck squamous cell carcinoma: Variation within and across primary tumor sites, and implications for antigen-specific immunotherapy.

BACKGROUND: The purpose of this study is to describe human epidermal growth factor 2 (HER2) overexpression in head and neck squamous cell carcinoma (HNSCC) and re-evaluate its potential as a target for HER2-directed immunotherapies. METHODS: A retrospective cohort of patients with HNSCC receiving curative treatment was identified, and HER2 expression evaluated in archival tissue by immunohistochemistry and correlated with clinicopathological characteristics. HER2 expression data were also determined for HNSCC patients in The Cancer Genome Atlas. RESULTS: Nineteen percent of HNSCC and 39% of oropharyngeal HNSCC (OPSCC) were HER2 positive. HER2 expression positively correlated with nodal metastasis (p = 0.035). Patients with HER2-positive tumors had decreased overall survival (p = 0.012), including within the human papilloma virus-positive OPSCC subgroup (p = 0.007). CONCLUSIONS: A substantial fraction of HNSCC overexpresses HER2 protein, suggesting it may be a suitable target for antigen-directed immunotherapy. HER2 expression and its correlation with survival vary across HNSCC subsites, making it unsuitable as a prognostic marker.

Spatially-resolved intracellular sensing of hydrogen peroxide in living cells.

Understanding intracellular redox chemistry requires new tools for the site-specific visualization of intracellular oxidation. We have developed a spatially-resolved intracellular sensor of hydrogen peroxide, HyPer-Tau, for time-resolved imaging in live cells. This sensor consists of a hydrogen peroxide-sensing protein tethered to microtubules. We demonstrate the use of the HyPer-Tau sensor for three applications; dose-dependent response of human cells to exogenous hydrogen peroxide, a model immune response of mouse macrophages to stimulation by bacterial toxin, and a spatially-resolved response to localized delivery of hydrogen peroxide. These results demonstrate that HyPer-Tau can be used as an effective tool for tracking changes in spatially localized intracellular hydrogen peroxide and for future applications in redox signaling.

Cellular binding of nanoparticles disrupts the membrane potential.

All cells generate an electrical potential across their plasma membrane driven by a concentration gradient of charged ions. A typical resting membrane potential ranges from -40 to -70 mV, with a net negative charge on the cytosolic side of the membrane. Maintenance of the resting membrane potential depends on the presence of two-pore-domain potassium "leak" channels, which allow for outward diffusion of potassium ions along their concentration gradient. Disruption of the ion gradient causes the membrane potential to become more positive or more negative relative to the resting state, referred to as "depolarization" or "hyperpolarization," respectively. Changes in membrane potential have proven to be pivotal, not only in normal cell cycle progression but also in malignant transformation and tissue regeneration. Using polystyrene nanoparticles as a model system, we use flow cytometry and fluorescence microscopy to measure changes in membrane potential in response to nanoparticle binding to the plasma membrane. We find that nanoparticles with amine-modified surfaces lead to significant depolarization of both CHO and HeLa cells. In comparison, carboxylate-modified nanoparticles do not cause depolarization. Mechanistic studies suggest that this nanoparticle-induced depolarization is the result of a physical blockage of the ion channels. These experiments show that nanoparticles can alter the biological system of interest in subtle, yet important, ways.