Community- and Patient-Partner Engagement in Women's Cardiovascular Disease Research: A Rapid Review of the Evidence.

The primary objective of this rapid review is to describe community-partner and patient-partner engagement in women's cardiovascular disease (CVD) research. Secondary objectives are to: (i) describe the phase of the research in which community and patient partners were engaged; (ii) define the level of engagement at each research phase; and (iii) make recommendations for future engagement of community and/or patient partners in women's CVD research. Rapid review guidelines recommended by the Cochrane Rapid Reviews Methods Group and Tricco et al. were used to search 5 databases using medical subject headings (MeSH) and/or keywords. Participants included women (cis and trans) aged > 18 years who had ischemic heart disease, heart failure, or stroke. A risk of bias assessment was not undertaken. Findings are summarized and/or clustered as community-based participatory research, or patient-oriented and/or patient-partner research. Our search yielded 39,998 titles and abstracts. Of these, 35 were included in a final narrative synthesis, comprising data from 474 community and/or patient partners, including 417 (88%) women. Over 85% of community partners collaborated in the design and/or planning and implementation of women's CVD research; most originated in the US; only one originated in Canada. Most patient-oriented and patient-partner research originated in Canada. However, less than 50% of patient partners collaborated in any phase of research. Sex, gender, race, and ethnicity were rarely reported. Results suggest negligible community and inadequate patient-oriented and/or patient-partner engagement in women's CVD research in Canada. Improved CVD outcomes for women may be achieved with better community- and patient-partner collaboration across all phases of research, genders, race, and ethnicities.

L'objectif principal de cette brève revue de littérature est de décrire l'engagement des partenaires communautaires et des patients partenaires dans la recherche sur les maladies cardiovasculaires (MCV) chez les femmes. Les objectifs secondaires sont les suivants (i) décrire la phase de la recherche dans laquelle la communauté et les patients partenaires ont été impliqués; (ii) définir le niveau d'engagement à chaque phase de la recherche; et (iii) formuler des recommandations pour l'engagement futur des partenaires communautaires et/ou des patients partenaires dans la recherche sur les MCV chez les femmes. Les lignes directrices pour effectuer des revues de littérature rapides recommandées par le Cochrane Rapid Reviews Methods Group et Tricco et coll. ont été utilisées pour effectuer des recherches dans 5 bases de données à l'aide de rubriques médicales sous-jacentes (MeSH) et/ou de mots-clés. Les participants étaient des femmes (cis et trans) âgées de plus de 18 ans et ayant eu une cardiopathie ischémique, une insuffisance cardiaque ou un accident vasculaire cérébral. Aucune évaluation du risque de biais n'a été entreprise. Les résultats sont résumés et/ou regroupés en tant que recherche communautaire participative, ou recherche orientée vers le patient et/ou recherche avec partenariat patient. Notre recherche a collecté 39 998 titres et résumés. Parmi ceux-ci, 35 ont été inclus dans une synthèse narrative finale, comprenant des données provenant de 474 partenaires communautaires et/ou patients, dont 417 (88%) femmes. Plus de 85% des partenaires communautaires ont collaboré à la conception et/ou à la planification et à la mise en œuvre de la recherche sur les MCV chez les femmes; la plupart étaient originaires des États-Unis; une étude seulement était originaire du Canada. La plupart des recherches axées sur le patient et sur les patients partenaires ont été menées au Canada. Cependant, moins de 50 % des patients partenaires ont collaboré à l'une ou l'autre phase de la recherche. Le sexe, le genre, la race et l'origine ethnique étaient rarement rapportés. Les résultats suggèrent un engagement négligeable des communautés et un engagement insuffisant des patients et/ou des patients partenaires dans la recherche sur les MCV chez les femmes au Canada. Une meilleure collaboration entre la communauté et les patients partenaires à toutes les étapes de la recherche, quel que soit le sexe, la race ou l'origine ethnique, permettrait d'améliorer les résultats de la recherche sur les MCV chez les femmes.

The Women@Heart NS Pilot Project: Rationale and Design of a Community-Based Peer Support Program for Women Living With Heart Disease in Nova Scotia.

Cardiac rehabilitation is associated with lower mortality and improved psychosocial outcomes. However, disparities exist in referral and access to cardiac rehabilitation for Nova Scotian women, a situation exacerbated by the COVID-19 pandemic. Women@Heart (W@H) is a 4-month community-based peer support program developed and validated by the University of Ottawa Heart Institute, for women living with heart disease. The program aims to empower women with coping strategies, provide a supportive learning environment, and establish volunteer advocacy groups. The primary objective of this study is to evaluate the implementation feasibility of the W@H program for women living in Nova Scotia. The primary outcome is the implementation feasibility of W@H in Nova Scotia, measured through participant attendance and program completion rates. Peer leaders will record participant attendance. The psychosocial impact of W@H will be assessed using psychometric tools that measure the following: social support, adaptive coping, stress, symptoms of anxiety and depression, and health-related and disease-specific quality of life. Data will be collected using a pre- and post-program questionnaire administered to participants. The pilot program is expected to commence in the first quarter of 2024. One peer leader with lived experience of heart disease, who has previously completed the W@H program as a participant, has been trained. Participants have been identified through healthcare provider referral, self-referral, brochures, and peer-networking. Each cohort will consist of 5-10 participants. The W@H pilot project will assess the implementation feasibility and the impact of community-based peer support on the well-being of Nova Scotian women living with heart disease.

La réadaptation cardiaque est associée à une mortalité plus faible et à des bienfaits psychosociaux. Cependant, il existe des disparités en ce qui a trait à l'orientation et à l'accès à la réadaptation cardiaque pour les femmes de la Nouvelle-Écosse, une situation exacerbée par la pandémie de COVID-19. Femmes@Cœur est un programme de soutien collectif par les pairs, créé et validé par l'Institut de cardiologie de l'Université d'Ottawa, à l'intention des femmes atteintes d'une maladies du cœur. Le programme vise à autonomiser les femmes en leur proposant des stratégies d'adaptation, à leur fournir un environnement propice à l'apprentissage et à former des groupes de bénévoles pour la défense de leurs intérêts. La présente étude a pour principal objectif d'évaluer la faisabilité de la mise en œuvre du programme Femmes@Cœur pour les femmes de la Nouvelle-Écosse. Le critère d'évaluation principal de l'étude est la faisabilité de la mise en œuvre du programme Femmes@Cœur en Nouvelle-Écosse, déterminée par la mesure des taux de participation et d'achèvement du programme. Des responsables parmi les pairs consigneront la présence des participantes. Les répercussions psychosociales du programme Femmes@Cœur seront évaluées à l'aide d'outils psychométriques mesurant une gamme de paramètres : soutien social, stratégies d'adaptation, niveau de stress, symptômes d'anxiété et de dépression, et qualité de vie liée à la santé et à la maladie en question. Les données seront recueillies au moyen de questionnaires administrés aux participantes avant et après le programme, et le projet pilote devrait être lancé le premier trimestre de 2024. Une responsable parmi les pairs, elle-même atteinte d'une maladie du cœur et ayant déjà pris part au programme Femmes@Cœur en tant que participante, a été formée à cet effet. Les participantes ont été trouvées de diverses façons : orientation par un professionnel de la santé, inscription spontanée, brochures et réseautage entre pairs. Chaque cohorte sera par ailleurs composée de 5 à 10 participantes. Enfin, le projet pilote Femmes@Cœur évaluera la faisabilité de la mise en œuvre et les répercussions du soutien collectif entre pairs sur le bien-être des femmes de la Nouvelle-Écosse atteintes de maladies cardiaques.

Autocrine-derived epidermal growth factor receptor ligands contribute to recruitment of tumor-associated macrophage and growth of basal breast cancer cells in vivo.

Epidermal growth factor receptor (EGFR) expression has been linked to progression of basal breast cancers. Many breast cancer cells harbor the EGFR and produce its family of ligands, suggesting they may participate in autocrine and paracrine signaling with cells of the tumor microenvironment. EGFR ligand expression was profiled in the basal breast cancer cell line MDA-231 where AREG, TGF-alpha, and HBEGF were the three ligands most highly expressed. Autocrine signaling was modulated through silencing or overexpression of these three ligands using lentiviral constructs and the impact measured using motility, proliferation, and cytokine expression assays. Changes in receptor phosphorylation and receptor turnover were examined. Knockdown of AREG or TGF-alpha in vitro resulted in decreased motility (p < 0.05) and decreased expression of macrophage chemoattractants. Overexpression of TGF-alpha increased motility and chemoattractant expression, whereas AREG did not. HBEGF modulation had no effect on any cellular behaviors. All the cells with altered ligand production were inoculated into female athymic nude mice to form mammary fat pad tumors, followed by immunohistochemical analysis for necrosis, angiogenesis, and macrophage recruitment. In vivo, knockdown of AREG or TGF-alpha increased survival (p < 0.001) while decreasing angiogenesis (p < 0.001), tumor growth (p < 0.001), and macrophage attraction (p < 0.001). Overexpression of AREG appeared to elicit a greater effect than TGF-alpha on mammary fat pad tumor growth by increasing angiogenesis (p < 0.001) and macrophage attraction to the tumor (p < 0.01). We propose these changes in mammary tumor growth were the result of increased recruitment of macrophages to the tumor by cells with altered autocrine EGFR signaling. We conclude that AREG and TGF-alpha were somewhat interchangeable in their effects on EGFR signaling; however, TGF-alpha had a greater effect in vitro and AREG had a greater effect in vivo.

Mental health and well-being of unpaid caregivers: a cross-sectional survey protocol.

INTRODUCTION: Unpaid caregiving, care provided by family/friends, is a public health issue of increasing importance. COVID-19 worsened the mental health conditions of unpaid caregivers, increasing substance/drug use and early development of chronic disease. The impact of the intersections of race and ethnicity, sex, age and gender along with unpaid care work and caregivers' health and well-being is unknown. The aim of this study is to describe the inequities of caregiver well-being across the intersections of race and ethnicity, sex, age and gender using a cross-sectional survey design. METHODS AND ANALYSIS: We are collaborating with unpaid caregivers and community organisations to recruit a non-probability sample of unpaid caregivers over 18 years of age (n=525). Recruitment will focus on a target sample of 305 South Asian, Chinese and Black people living in Canada, who represent 60% of the Canadian racial and ethnic populations. The following surveys will be combined into one survey: Participant Demographic Form, Caregiver Well-Being Index, interRAI Self-report of Carer Needs and the GENESIS (GENdEr and Sex DetermInantS of Cardiovascular Disease: From Bench to Beyond-Premature Acute Coronary Syndrome) PRAXY Questionnaire. Sample characteristics will be summarised using descriptive statistics. The scores from the Caregiver Well-Being Index will be dichotomised into fair/poor and good/excellent. A two-stage analytical strategy will be undertaken using logistic regression to model fair/poor well-being and good/excellent well-being according to the following axes of difference set a priori: sex, race and ethnicity, gender identity, age, gender relations, gender roles and institutionalised gender. The first stage of analysis will model the main effects of each factor and in the second stage of analysis, interaction terms will be added to each model. ETHICS AND DISSEMINATION: The University of Toronto's Health Sciences Research Ethics Board granted approval on 9 August 2022 (protocol number: 42609). Knowledge will be disseminated in pamphlets/infographics/email listservs/newsletters and journal articles, conference presentation and public forums, social media and through the study website. TRIAL REGISTRATION NUMBER: This is registered in the Open Sciences Framework with a Registration DOI as follows: https://doi.org/10.17605/OSF.IO/PB9TD.

EGFR signaling in breast cancer: bad to the bone.

The epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases. This family includes EGFR/ErbB1/HER1, ErbB2/HER2/Neu ErbB3/HER3, and ErbB4/HER4. For many years it was believed that EGFR plays a minor role in the development and progression of breast malignancies. However, recent findings have led investigators to revisit these beliefs. Here we will review these findings and propose roles that EGFR may play in breast malignancies. In particular, we will discuss the potential roles that EGFR may play in triple-negative tumors, resistance to endocrine therapies, maintenance of stem-like tumor cells, and bone metastasis. Thus, we will propose the contexts in which EGFR may be a therapeutic target.

At the crossroads: EGFR and PTHrP signaling in cancer-mediated diseases of bone.

The epidermal growth factor receptor is a well-established cancer therapeutic target due to its stimulation of proliferation, motility, and resistance to apoptosis. Recently, additional roles for the receptor have been identified in growth of metastases. Similar to development, metastatic spread requires signaling interactions between epithelial-derived tumor cells and mesenchymal derivatives of the microenvironment. This necessitates reactivation of developmental signaling molecules, including the hypercalcemia factor parathyroid hormone-related protein. This review covers the variations of epidermal growth factor receptor signaling in cancers that produce bone metastases, regulation of parathyroid hormone-related protein, and evidence that the two molecules drive cancer-mediated diseases of bone.

Decreased autocrine EGFR signaling in metastatic breast cancer cells inhibits tumor growth in bone and mammary fat pad.

Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and osteoblast-like cells. Both paracrine and autocrine EGFR signaling were inhibited with a neutralizing amphiregulin antibody, PAR34, whereas shRNA to the EGFR was used to specifically block autocrine signaling in MDA-231 cells. The impact of these was evaluated with proliferation, migration and gene expression assays. Breast cancer metastasis to bone was modeled in female athymic nude mice with intratibial inoculation of MDA-231 cells, and cancer cell-bone marrow co-cultures. EGFR knockdown, but not PAR34 treatment, decreased osteoclasts formed in vitro (p<0.01), reduced osteolytic lesion tumor volume (p<0.01), increased survivorship in vivo (p<0.001), and resulted in decreased MDA-231 growth in the fat pad (p<0.01). Fat pad shEGFR-MDA-231 tumors produced in nude mice had increased necrotic areas and decreased CD31-positive vasculature. shEGFR-MDA-231 cells also produced decreased levels of the proangiogenic molecules macrophage colony stimulating factor-1 (MCSF-1) and matrix metalloproteinase 9 (MMP9), both of which were decreased by EGFR inhibitors in a panel of EGFR-positive breast cancer cells. Thus, inhibiting autocrine EGFR signaling in breast cancer cells may provide a means for reducing paracrine factor production that facilitates microenvironment support in the bone and mammary gland.