Emergency Knowledge Translation, COVID-19 and indoor air: evaluating a virtual ventilation and filtration consultation program for community spaces in Ontario.

BACKGROUND: An October, 2021 review of Public Health Ontario's COVID-19 guidance for congregate settings such as shelters and long-term care homes demonstrated that this guidance did not include references to ventilation or filtration. In April 2022, an interdisciplinary team with expertise in indoor air quality (IAQ), engineering, epidemiology, community programming and knowledge translation launched a virtual ventilation and filtration consultation program for community spaces in Toronto, Ontario. The program gives people working in community spaces direct access to IAQ experts through 25-min online appointments. The program aims to help reduce the risk of COVID-19 transmission in community spaces, and was designed to help compensate for gaps in public health guidance and action. METHODS: Representatives from participating organizations (n. 27) received a link to an online survey via email in April 2023. Survey questions explored the impacts of the program on topics such as: purchase and use of portable air filters; maintenance and use of bathroom fans; and, maintenance and modification of HVAC systems. Survey participation was anonymous, and no demographic information was collected from participants. RESULTS: Representatives from 11 organizations completed the survey (40%). Of those who responded, nine (82%) made changes as a result of the program, with eight (73%) making two or more changes such as purchasing portable air filters and increasing routine maintenance of HVAC systems. CONCLUSIONS: When presented with brief access to expert support and tailored plain language guidance, people working in community spaces increased their use of ventilation and filtration strategies for COVID-19 infection prevention and control.

Does P-glycoprotein contribute to amphotericin B epithelial transport in Caco-2 cells?

INTRODUCTION: Amphotericin B (AmB) is a highly efficacious therapeutic for invasive fungal infections and protozoal diseases. Increasing prevalence of these conditions warrants the development of an oral AmB formulation. Efflux transporters, such as the ABCB1 gene product P-glycoprotein, affect the oral bioavailability and disposition of a range of clinically relevant compounds. At present, it remains to be determined whether AmB is a substrate of P-glycoprotein mediated efflux. The objective of this study was to determine whether P-glycoprotein contributes to the epithelial transport of AmB in a Caco-2 cell model. METHODS: Stimulation of P-glycoprotein ATPase activity was assessed using membranes containing human recombinant P-glycoprotein. An ABCB1 knockdown Caco-2 cell model was employed to determine non-toxic concentrations of AmB. AmB cellular association, following a 180 min incubation, was determined using an high performance liquid chromatography-ultraviolet (HPLC-UV) assay. RESULTS: At the concentrations investigated, AmB did not stimulate P-glycoprotein ATPase activity. Non-toxic concentrations of AmB were 1 µg/mL-5 µg/mL; these were used in subsequent experiments. No significant difference in AmB cellular association was observed for ABCB1 small interfering ribonucleic acid transfected and non-transfected Caco-2 cells, following a 180 min incubation with 1 µg/mL and 2.5 µg/mL AmB. However, significantly greater AmB was associated with transfected cells as compared to non-transfected cells, when cells were incubated with 5 µg/mL AmB. CONCLUSIONS: These results suggest that AmB is not a substrate of P-glycoprotein mediated efflux in this Caco-2 cell model. P-glycoprotein is not expected to be a major barrier to the oral absorption and disposition of AmB.

Dose-dependent targeted suppression of P-glycoprotein expression and function in Caco-2 cells.

The efflux transporter P-glycoprotein (Pgp), encoded by the ABCB1 gene, decreases the bioavailability of a wide range of orally administered drugs. Drug permeability studies using the in vitro Caco-2 cell model commonly rely on small molecule modulators to estimate the contribution of Pgp to drug efflux. The use of such modulators may be limited by their interactions with other membrane transporters. RNA interference, a tool allowing for the specific degradation of a target gene's mRNA, has emerged as a technique to study gene expression and function. This manuscript describes the use of chemically modified small interfering RNA (siRNA) for a dose-dependent suppression of ABCB1 in Caco-2 cells and the subsequent drug permeability assay. We transfected Caco-2 cells while in suspension with chemically modified synthetic siRNA-lipid complexes and then seeded the cells on polycarbonate semipermeable supports. Once the monolayer of Caco-2 cells formed tight junctions and expressed brush border enzymes, we determined the dose-dependent suppression of the ABCB1 gene using RT-qPCR. We measured the duration of silencing at the optimal siRNA dose by Western blot for Pgp protein. The utility of this in vitro model was determined by performing bidirectional transport studies using a well-established substrate for Pgp, rhodamine 123. A single 4 h transfection of the Caco-2 cells with ≥100 nM siRNA reduced the expression of ABCB1 mRNA by >85% at day five in culture. The time-course study revealed that the single transfection reduces Pgp protein levels for 9 days in culture. This magnitude of silencing was sufficient to reduce the efflux of rhodamine 123 as measured by the apparent permeability coefficient and intracellular accumulation. In this study, we demonstrate the dose-dependent, targeted degradation of Pgp in Caco-2 cells as a new model for assessing drug efflux from enterocytes. The dose-dependent nature of the Pgp silencing in this study offers significant improvements over other approaches to creating a Caco-2 model with suppressed ABCB1 expression. We envision that this technique, in conjunction with better small molecule inhibitors, will provide a useful tool for future drug permeability studies.

Impact of Project ECHO on Patient and Community Health Outcomes: A Scoping Review.

PURPOSE: Project Extension for Community Healthcare Outcomes (ECHO) is a hub-and-spoke tele-education model that aims to increase health care providers' access to evidence-based guidelines and enhance their capacity to care for complex patients in rural, remote, and underserved communities. The purpose of this scoping review was to examine evidence of the impact of Project ECHO programs on patient and community health outcomes. METHOD: The authors used Arksey and O'Malley's framework and subsequent revisions proposed by Levac and colleagues to guide their review. They searched MEDLINE, EMBASE, CINAHL Plus, and Web of Science for English-language, peer-reviewed articles published between January 2003 and June 2020. Included studies focused on Project ECHO programs and reported either patient or community health outcomes. The authors used a standardized data extraction form to document bibliographical information and study characteristics, including health outcome level(s), as articulated by Moore's evaluation framework for continuing medical education. RESULTS: Of the 597 search results, the authors identified 15 studies describing Project ECHO programs. These programs were implemented in the United States and Australia and facilitated education sessions with health care providers caring for adult patients living with 1 of 7 medical conditions. Included study findings suggest Project ECHO programs significantly changed patient-level outcomes (n = 15) and to a lesser extent changed community-level outcomes (n = 1). Changes in care were observed at the individual patient level, at the practice level, and in objective clinical measures, including sustained virologic response and HbA1c. CONCLUSIONS: This review identified emerging evidence of the effectiveness of Project ECHO as a tele-education model that improves patient health outcomes and has the potential to positively impact community health. The small number of included studies suggests that additional evidence of patient- and community-level impact is required to support the continued adoption and implementation of this model.

Differences in Breast Cancer Presentation at Time of Diagnosis for Black and White Women in High Resource Settings.

This paper provides a narrative review of the existing literature on differences in demographic and biological features of breast cancer at time of diagnosis between Black and White women in Canada, the United Kingdom and the United States. Electronic database searches for published peer-reviewed articles on this topic were conducted, and 78 articles were included in the final narrative review. Differences between Black and White women were compared for eight categories including age, tumour stage, size, grade, lymph node involvement, and hormone status. Black women were significantly more likely to present with less favourable tumour features at the time of diagnosis than White women. Significant differences were reported in age at diagnosis, tumour stage, size, grade and hormone status, particularly triple negative breast cancer. Limitations on the generalizability of the review findings are discussed, as well as the implications of these findings on future research, especially within the Canadian context.

Pediatric Project ECHO®: A Virtual Community of Practice to Improve Palliative Care Knowledge and Self-Efficacy among Interprofessional Health Care Providers.

Background: Health care providers (HCPs) require ongoing training and mentorship to fully appreciate the palliative care needs of children. Project ECHO® (Extension for Community Healthcare Outcomes) is a model for delivering technology-enabled interprofessional education and cultivating a community of practice among HCPs who care for children with life-limiting illness. Objectives: To develop, implement, and evaluate the Project ECHO model within the pediatric palliative care (PPC) context. Specific objectives were to evaluate (1) participation levels, (2) program acceptability, (3) HCP knowledge changes, (4) HCP self-efficacy changes, and (5) perceived practice changes after six months. Intervention: An interprofessional PPC curriculum was informed by a needs assessment. The curriculum was delivered through monthly virtual 90-minute TeleECHO sessions (didactic presentation and case-based learning) from January 2018 to December 2019. The program was freely available to all HCPs wishing to participate. Design: A mixed-methods design with repeat measures was used. Surveys were distributed at baseline and six months to assess outcomes using 7-point Likert scales. Descriptive and inferential statistical analyses were conducted. The study was approved by the Research Ethics Board at the Hospital for Sick Children. Results: Twenty-four TeleECHO sessions were completed with a mean of 32 ± 12.5 attendees. Acceptability scores (n = 43) ranged from 5.1 ± 1.1 to 6.5 ± 0.6. HCPs reported improvements in knowledge and self-efficacy across most topics (11 out of 12) and skills (8 out of 10) with demonstrated statistical significance (p < 0.05). Most participants reported positive practice impacts, including enhanced ability to provide PPC in their practice. Conclusion: Project ECHO is a feasible and impactful model for fostering a virtual PPC-focused community of practice among interprofessional HCPs.

Pediatric Project ECHO: Implementation of a Virtual Medical Education Program to Support Community Management of Children With Medical Complexity.

OBJECTIVES: Health care providers (HCPs) require ongoing support to meet the evolving care needs of children with medical complexity (CMC). Project Extension for Community Healthcare Outcomes (ECHO) is a model for delivering technology-enabled medical education and cultivating a community of practice. In this study, we focused on developing, implementing, and evaluating the first ECHO program dedicated to the care of CMC. Specific objectives were to evaluate the program feasibility (participation and acceptability) and impact on perceived HCP knowledge, self-efficacy, and clinical practice after 6 months. METHODS: A needs assessment was conducted to inform an interprofessional CMC curriculum. This curriculum was delivered through monthly virtual TeleECHO clinics (didactic and case-based learning) from January 2018 to 2020. The program was available at no cost to HCPs throughout Ontario. Surveys were distributed at baseline and 6 months to assess program acceptability, knowledge, self-efficacy, and practice impact by using 7-point Likert scales. Descriptive and inferential data analyses were conducted. RESULTS: Twenty-four clinics were completed with a mean of 19 ± 6 attendees. Acceptability scores (n = 27) ranged from 5.0 ± 1.1 to 6.4 ± 0.6. Participants reported an improvement in their knowledge and self-efficacy across all probed topics and skills (P values ranged from <.001 to .006). These knowledge and self-efficacy scores related to "complex care support," "feeding support," and "respiratory support." The majority of participants reported positive or very positive practice impacts, including enhanced ability to provide quality care to CMC. CONCLUSIONS: Project ECHO is a feasible and acceptable model for virtual education of interprofessional HCPs in managing CMC. This program has the potential to increase system capacity to provide quality care to CMC close to home.

Neglected populations: safeguarding the health of street-involved children in Ghana.

Ensuring the health of street-involved children is a growing public health challenge. These children are vulnerable, neglected, and rarely a priority for basic service providers and governments. Sizable populations of street-involved children are present in major urban areas worldwide and current trends in urbanization suggest these populations will grow in the coming years. Although migration offers employment and training opportunities, the health and wellbeing of children is negatively impacted by their interactions with the streets. However, systemic barriers may also prevent these children from achieving an adequate health status. The situation of street-involved children in Ghana, West Africa will be discussed.