EfgA is a conserved formaldehyde sensor that leads to bacterial growth arrest in response to elevated formaldehyde.

Normal cellular processes give rise to toxic metabolites that cells must mitigate. Formaldehyde is a universal stressor and potent metabolic toxin that is generated in organisms from bacteria to humans. Methylotrophic bacteria such as Methylorubrum extorquens face an acute challenge due to their production of formaldehyde as an obligate central intermediate of single-carbon metabolism. Mechanisms to sense and respond to formaldehyde were speculated to exist in methylotrophs for decades but had never been discovered. Here, we identify a member of the DUF336 domain family, named efgA for enhanced formaldehyde growth, that plays an important role in endogenous formaldehyde stress response in M. extorquens PA1 and is found almost exclusively in methylotrophic taxa. Our experimental analyses reveal that EfgA is a formaldehyde sensor that rapidly arrests growth in response to elevated levels of formaldehyde. Heterologous expression of EfgA in Escherichia coli increases formaldehyde resistance, indicating that its interaction partners are widespread and conserved. EfgA represents the first example of a formaldehyde stress response system that does not involve enzymatic detoxification. Thus, EfgA comprises a unique stress response mechanism in bacteria, whereby a single protein directly senses elevated levels of a toxic intracellular metabolite and safeguards cells from potential damage.

Barriers to cancer treatment for people experiencing socioeconomic disadvantage in high-income countries: a scoping review.

BACKGROUND: Despite advances in cancer research and treatment, the burden of cancer is not evenly distributed. People experiencing socioeconomic disadvantage have higher rates of cancer, later stage at diagnoses, and are dying of cancers that are preventable and screen-detectable. However, less is known about barriers to accessing cancer treatment. METHODS: We conducted a scoping review of studies examining barriers to accessing cancer treatment for populations experiencing socioeconomic disadvantage in high-income countries, searched across four biomedical databases. Studies published in English between 2008 and 2021 in high-income countries, as defined by the World Bank, and reporting on barriers to cancer treatment were included. RESULTS: A total of 20 studies were identified. Most (n = 16) reported data from the United States, and the remaining included publications were from Canada (n = 1), Ireland (n = 1), United Kingdom (n = 1), and a scoping review (n = 1). The majority of studies (n = 9) focused on barriers to breast cancer treatment. The most common barriers included: inadequate insurance and financial constraints (n = 16); unstable housing (n = 5); geographical distribution of services and transportation challenges (n = 4); limited resources for social care needs (n = 7); communication challenges (n = 9); system disintegration (n = 5); implicit bias (n = 4); advanced diagnosis and comorbidities (n = 8); psychosocial dimensions and contexts (n = 6); and limited social support networks (n = 3). The compounding effect of multiple barriers exacerbated poor access to cancer treatment, with relevance across many social locations. CONCLUSION: This review highlights barriers to cancer treatment across multiple levels, and underscores the importance of identifying patients at risk for socioeconomic disadvantage to improve access to treatment and cancer outcomes. Findings provide an understanding of barriers that can inform future, equity-oriented policy, practice, and service innovation.

Advancing evidence-based practice through the Knowledge Translation Challenge: Nurses' important roles in research, implementation science and practice change.

AIM: To describe a knowledge translation capacity-building initiative and illustrate the roles of nurses in practice change using an exemplar case study. DESIGN: The report uses observational methods and reflection. METHODS: The Knowledge Translation Challenge program involves a multi-component intervention across several sites. The advisory committee invited eligible teams to attend capacity-building workshops. Implementation plans were developed, and successful teams receive funding for a 2 year period. Evaluation involved collecting data on program uptake and impact on practice change. Data has been collected from five cohorts. The exemplar case study employed an action-research framework. RESULTS: Four nurse-led teams have demonstrated successful implementation of their practice change. The case study on implementing a clinical toolkit for clozapine management further illustrates a thoughtful planning process, and implementation journey and learnings by a team of nurses. CONCLUSION: The Knowledge Translation Challenge program empowers nurses to use implementation science practices to enhance the quality and effectiveness of healthcare services. Success of this initiative serves as a model for addressing the persistent gap between knowledge and practice in clinical settings and the value of activating nurses to help close this gap. IMPLICATIONS: As the most trusted and numerous profession, it is vital that nurses contribute to efforts to translate research evidence into clinical practice. The Knowledge Translation Challenge program supports nurses to lead practice change. IMPACT: The Knowledge Translation Challenge program successfully equips nurses and other health care providers with the knowledge, skills and resources to implement practice improvements which enhance the quality and effectiveness of healthcare services and nursing practice. PATIENT OR PUBLIC CONTRIBUTION: The Knowledge Translation Challenge advisory committee has three patient-public partners that support teams to develop a patient-oriented approach for their projects by providing feedback on the implementation plans. Each team was also supported to include patient-public partners on their project.

Barriers to cancer treatment and care for people experiencing structural vulnerability: a secondary analysis of ethnographic data.

BACKGROUND: A key pillar of Canada's healthcare system is universal access, yet significant barriers to cancer services remain for people impacted by structural vulnerability (e.g., poverty, homelessness, racism). For this reason, cancer is diagnosed at a later stage, resulting in worse patient outcomes, a reduced quality of life, and at a higher cost to the healthcare system. Those who face significant barriers to access are under-represented in cancer control services Consequently, these inequities result in people dying from cancers that are highly treatable and preventable, however; little is known about their treatment and care course. The aim of this study was to explore barriers to accessing cancer treatment among people experiencing structural vulnerability within a Canadian context. METHODS: We conducted a secondary analysis of ethnographic data informed by critical theoretical perspectives of equity and social justice. The original research draws from 30 months of repeated interviews (n = 147) and 300 h of observational fieldwork with people experiencing health and social inequities at the end-of-life, their support persons, and service providers. RESULTS: Our analysis identified four themes presenting as 'modifiable' barriers to inequitable access to cancer treatment: (1) housing as a key determinant for cancer treatment (2) impact of lower health literacy (3) addressing social care needs is a pre-requisite for treatment (4) intersecting and compounding barriers reinforce exclusion from cancer care. These inter-related themes point to how people impacted by health and social inequities are at times 'dropped' out of the cancer system and therefore unable to access cancer treatment. CONCLUSION: Findings make visible the contextual and structural factors contributing to inequitable access to cancer treatment within a publically funded healthcare system. Identifying people who experience structural vulnerability, and approaches to delivering cancer services that are explicitly equity-oriented are urgently needed.

Health and healthcare equity within the Canadian cancer care sector: a rapid scoping review.

BACKGROUND: Despite a publicly-funded healthcare system, alarming cancer-related health and healthcare inequities persist in Canada. However, it remains unclear how equity is being understood and taken up within the Canadian cancer context. Our objective was to identify how health and healthcare equity are being discussed as goals or aims within the cancer care sector in Canada. METHODS: A rapid scoping review was conducted; five biomedical databases, 30 multidisciplinary websites, and Google were searched. We included English-language documents published between 2008 and 2021 that discussed health or healthcare equity in the Canadian cancer context. RESULTS: Of 3860 identified documents, 83 were included for full-text analysis. The prevalence of published and grey equity-oriented literature has increased over time (2008-2014 [n = 20]; 2015-2021 [n = 62]). Only 25% of documents (n = 21) included a definition of health equity. Concepts such as inequity, inequality and disparity were frequently used interchangeably, resulting in conceptual muddling. Only 43% of documents (n = 36) included an explicit health equity goal. Although a suite of actions were described across the cancer control continuum to address equity goals, most were framed as recommendations rather than direct interventions. CONCLUSION: Health and healthcare equity is a growing priority in the cancer care sector; however, conceptual clarity is needed to guide the development of robust equity goals, and the development of sustainable, measurable actions that redress inequities across the cancer control continuum. If we are to advance health and healthcare equity in the cancer care sector, a coordinated and integrated approach will be required to enact transformative and meaningful change.

Patient-reported mental health and well-being trajectories in oncology patients during radiation therapy: an exploratory retrospective cohort analysis using the Ontario Cancer Registry.

PURPOSE: Mental health and well-being trajectories are not expected to be homogeneous in diverse clinical populations. This exploratory study aims to identify subgroups of patients with cancer receiving radiation therapy who have different mental health and well-being trajectories, and examine which socio-demographic, physical symptoms, and clinical variables are associated with such trajectories. METHODS: Retrospective analysis of radiation therapy patients diagnosed with cancer in 2017 was conducted using data from the Ontario Cancer Registry (Canada) and linked with administrative health data. Mental health and well-being were measured using items from the Edmonton Symptom Assessment System-revised questionnaire. Patients completed up to 6 repeated measurements. We used latent class growth mixture models to identify heterogeneous mental health trajectories of anxiety, depression, and well-being. Bivariate multinomial logistic regressions were conducted to explore variables associated with the latent classes (subgroups). RESULTS: The cohort (N = 3416) with a mean age of 64.5 years consisted of 51.7% females. Respiratory cancer was the most common diagnosis (30.4%) with moderate to severe comorbidity burden. Four latent classes with distinct anxiety, depression, and well-being trajectories were identified. Decreasing mental health and well-being trajectories are associated with being female; living in neighborhoods with lower income, greater population density, and higher proportion of foreign-born individuals; and having higher comorbidity burden. CONCLUSIONS: The findings highlight the importance of considering social determinants of mental health and well-being, in addition to symptoms and clinical variables, when providing care for patients undergoing radiation therapy.

Formaldehyde-responsive proteins, TtmR and EfgA, reveal a tradeoff between formaldehyde resistance and efficient transition to methylotrophy in Methylorubrum extorquens.

For bacteria to thrive they must be well-adapted to their environmental niche, which may involve specialized metabolism, timely adaptation to shifting environments, and/or the ability to mitigate numerous stressors. These attributes are highly dependent on cellular machinery that can sense both the external and intracellular environment. Methylorubrum extorquens is an extensively studied facultative methylotroph, an organism that can use single-carbon compounds as their sole source of carbon and energy. In methylotrophic metabolism, carbon flows through formaldehyde as a central metabolite; thus, formaldehyde is both an obligate metabolite and a metabolic stressor. Via the one-carbon dissimilation pathway, free formaldehyde is rapidly incorporated by formaldehyde activating enzyme (Fae), which is constitutively expressed at high levels. In the presence of elevated formaldehyde levels, a recently identified formaldehyde-sensing protein, EfgA, induces growth arrest. Herein, we describe TtmR, a formaldehyde-responsive transcription factor that, like EfgA, modulates formaldehyde resistance. TtmR is a member of the MarR family of transcription factors and impacts the expression of 75 genes distributed throughout the genome, many of which are transcription factors and/or involved in stress response, including efgA Notably, when M. extorquens is adapting its metabolic network during the transition to methylotrophy, efgA and ttmR mutants experience an imbalance in formaldehyde production and a notable growth delay. Although methylotrophy necessitates that M. extorquens maintain a relatively high level of formaldehyde tolerance, this work reveals a tradeoff between formaldehyde resistance and the efficient transition to methylotrophic growth and suggests that TtmR and EfgA play a pivotal role in maintaining this balance.Importance: All organisms produce formaldehyde as a byproduct of enzymatic reactions and as a degradation product of metabolites. The ubiquity of formaldehyde in cellular biology suggests all organisms have evolved mechanisms of mitigating formaldehyde toxicity. However, formaldehyde-sensing is poorly described and prevention of formaldehyde-induced damage is primarily understood in the context of detoxification. Here we use an organism that is regularly exposed to elevated intracellular formaldehyde concentrations through high-flux one-carbon utilization pathways to gain insight into the role of formaldehyde-responsive proteins that modulate formaldehyde resistance. Using a combination of genetic and transcriptomic analyses, we identify dozens of genes putatively involved in formaldehyde resistance, determined the relationship between two different formaldehyde response systems and identified an inherent tradeoff between formaldehyde resistance and optimal transition to methylotrophic metabolism.

A survey of health care practitioners' attitudes toward shared decision-making for choice of next birth after cesarean.

BACKGROUND: Patients with a history of cesarean may benefit from shared decision-making (SDM) interventions, such as patient decision aids, that provide individualized clinical information and help to clarify personal preferences. We sought to understand the factors that influence how care practitioners support choices for mode of birth and what individual and health system factors influence uptake of SDM in routine care. METHODS: We conducted a cross-sectional survey of health care practitioners in British Columbia, Canada (2016-2017). Participants included family physicians, midwives, obstetricians, and registered nurses. We conducted descriptive and inferential analyses of quantitative data and subjected the open-ended survey responses to thematic analysis. RESULTS: Analysis of survey responses (n = 307) suggested there was no significant association between the size of the participant hospital and their medico-legal concerns about mode of birth. Environmental factors that may influence the use of SDM included the length of time it takes to initiate an emergency cesarean and the timing of when the SDM intervention is introduced to the patient. No participants reported protocols prohibiting VBAC at their hospital. Participants preferred an SDM approach where the pregnant person is involved in making the final decision for mode of birth. CONCLUSIONS: Although maternity care practitioners express attitudes and behaviors that may support SDM for mode of birth after cesarean, implementing SDM using a patient decision aid alone may be challenging because of environmental factors. Our study demonstrates how survey data can aid in identifying how, when, where, for whom, and why an SDM intervention could be implemented.

It's not an easy fix: Adherence to adjuvant endocrine therapy after breast cancer.

Adjuvant endocrine therapy (AET) is a highly efficacious treatment that significantly reduces breast cancer recurrence and mortality for women with hormone-receptor positive breast cancer. Yet, many women do not adhere to prescribed AET. The overarching aim of this research was to gain a better understanding of why a significant number of women diagnosed with breast cancer have suboptimal adherence to AET. A mixed-methods approach was used to explore the personal, social, and structural factors influencing breast cancer survivors' AET adherence, including: (1) an integrative review of patient-reported factors associated with AET adherence; and (2) interviews with breast cancer survivors prescribed AET. In this paper, we summarize and discuss the key contributions of both phases of this research, implication for clinical practice, and how we might leverage the expertise of nurses in practicing to full scope to address the complex needs of breast cancer survivors prescribed AET.

Improving the outcomes for cancer survivors in Canada: An interactive approach to competency development using the newly released CANO/ACIO Survivorship Manual.

CANO/ACIO has long recognized the important role oncology nurses play in improving outcomes for cancer survivors. To ensure oncology nurses have easy access to the updated evidence, as a basis for their practice, CANO/ACIO undertook the important work of updating the CANO/ACIO self-learning modules on survivorship and creating several new ones. This article highlights the current gaps in care experienced by cancer survivors in the months and years after their cancer treatments are completed and the important contributions that nurses can have in improving the quality of survivorship care. It also provides an interactive approach to competency development using the newly revised and rereleased Pan-Canadian Survivorship Manual.

Patient-reported factors associated with adherence to adjuvant endocrine therapy after breast cancer: an integrative review.

BACKGROUND: Adjuvant endocrine therapy (AET) significantly reduces recurrence and mortality in women with breast cancer (BrCa). Despite the efficacy of AET in improving BrCa outcomes, up to 50% of women do not adhere to prescribed AET regimens. While numerous demographic and clinical predictors influence adherence and persistence, few studies have identified the patient-reported factors that influence AET adherence and persistence. PURPOSE: The aim was to examine the patient-reported personal, social, and structural factors influencing BrCa survivors' adherence and persistence with AET. METHODS: An integrative review was undertaken wherein PubMed, Medline, CINAHL, Embase, and PsycINFO databases were searched using keyword descriptors and database subject headings. Inclusion criteria included quantitative or qualitative peer-reviewed studies written in English that assessed AET adherence and/or persistence through objective measurement or self-report and included patient-reported factors found to influence adherence and/or persistence. The data extracted from eligible studies were entered into a matrix, and systematically compared and iteratively analyzed using relational autonomy as an organizing theoretical framework. RESULTS: A total of 43 manuscripts (9 qualitative and 34 quantitative) were reviewed. Several personal, social, and structural factors were identified that influenced AET adherence and persistence, including side effects, necessity beliefs, self-efficacy, the patient-healthcare provider relationship, social support, and continuity of follow-up care. CONCLUSIONS: An increasing number of studies have focused on identifying the patient-reported factors that influence AET adherence and persistence. This review highlights important personal, social, and structural factors that act as facilitators and barriers in adhering to and persisting with long-term AET. Acknowledging and addressing these factors is key to providing women with the care needed to improve suboptimal adherence and persistence.

Understanding adjuvant endocrine therapy persistence in breast Cancer survivors.

BACKGROUND: Adjuvant endocrine therapy (AET) significantly decreases the risk of breast cancer recurrence and mortality. Notwithstanding the demonstrated efficacy of AET, 31-73% of breast cancer survivors do not persist with AET. The purpose of this study was to explore breast cancer survivors' experiences and perspectives of persisting with AET and to identify the psychosocial and healthcare system factors that influence AET persistence. METHODS: Informed by interpretive descriptive methodology and relational autonomy theory, individual interviews were conducted with 22 women diagnosed with early-stage breast cancer who had been prescribed AET. These participants also completed a demographic form and a survey that assessed their perceived risk of recurrence. Interviews were analysed using inductive thematic and constant comparative analysis to iteratively compare data and develop conceptualizations of the relationships among data. Descriptive statistics were used to summarize the quantitative data. RESULTS: The personal, social, and structural factors found to influence AET persistence included AET side effects, perception of breast cancer recurrence risk, medication and necessity beliefs, social support, the patient-provider relationship, and the continuity and frequency of follow-up care. For most women, over time, the decision-making process around AET persistence became a balancing act between quality of life and quantity of life. The interplay between the personal, social, and structural factors was complex and the weight women placed on some factors over others influenced their AET persistence or non-persistence. CONCLUSION: Expanding our understanding of the factors affecting breast cancer survivors' AET persistence from their perspective is the first step in developing efficacious, patient-centered interventions aimed at improving AET persistence. In order to improve AET persistence, enhanced symptom management is required, as well as the development of supportive care strategies that acknowledge the values and beliefs held by breast cancer survivors while reinforcing the benefits of AET, and addressing women's reasons for non-persistence. Improved continuity of health care and patient-healthcare provider communication across oncology and primary care settings is also required. The development and evaluation of supportive care strategies that address the challenges associated with AET experienced by breast cancer survivors hold the potential to increase both women's quality and quantity of life.

Building and sustaining a postgraduate student network: The experience of oncology nurses in Canada.

Networking with individuals on a similar journey through graduate studies has been identified as an important influence in the experience of doctoral and postdoctoral students. Through the Board of Directors of the Canadian Association of Nurses in Oncology/Association canadienne des infirmières en oncologie (CANO/ACIO), student members were encouraged to establish a Doctoral Student Network (DSN) that would enable a connection through education and common interest in oncology and cancer care. Since its inception, the DSN has been dynamic in how it has addressed the evolving needs of members and in providing development opportunities to group members. To uncover and describe key aspects of its evolution, a document analysis was undertaken to reveal themes pertaining to capacity development and leadership voice as paths to leadership for DSN members. The results of this study suggest that the DSN provides a supportive environment for postgraduate nurses across Canada to connect with others in their peer group to foster engagement in educational, professional, and scholarly activities, as well as highlighting opportunities for other professional organizations interested in establishing a support network for graduate student members.

Qualitative assessment of information and decision support needs for managing menopausal symptoms after breast cancer.

PURPOSE: For breast cancer (BrCa) survivors, premature menopause can result from conventional cancer treatment. Due to limited treatment options, survivors often turn to complementary therapies (CTs), but struggle to make informed decisions. In this study, we identified BrCa survivors' CT and general information and decision-making needs related to menopausal symptoms. METHODS: The needs assessment was informed by interpretive descriptive methodology. Focus groups with survivors (n = 22) and interviews with conventional (n = 12) and CT (n = 5) healthcare professionals (HCPs) were conducted at two Canadian urban cancer centers. Thematic, inductive analysis was conducted on the data. RESULTS: Menopausal symptoms have significant negative impact on BrCa survivors. Close to 70 % of the sample were currently using CTs, including mind-body therapies (45.5 %), natural health products (NHPs) and dietary therapies (31.8 %), and lifestyle interventions (36.4 %). However, BrCa survivors reported inadequate access to information on the safety and efficacy of CT options. Survivors also struggled in their efforts to discuss CT with HCPs, who had limited time and information to support women in their CT decisions. Concise and credible information about CTs was required by BrCa survivors to support them in making informed and safe decisions about using CTs for menopausal symptom management. CONCLUSIONS: High quality research is needed on the efficacy and safety of CTs in managing menopausal symptoms following BrCa treatment. Decision support strategies, such as patient decision aids (DAs), may help synthesize and translate evidence on CTs and promote shared decision-making between BrCa survivors and HCPs about the role of CTs in coping with menopause following cancer treatment.

Seeing the person before the numbers: Personas for understanding patients' life stories when using patient-reported outcome measures in practice settings.

AIMS: While patient-reported outcome measures (PROMs) are increasingly being integrated into health information technologies, one challenge has been to assist clinicians in understanding how the responses to PROMs relate to patient stories for identifying and addressing the care needs of individual patients. Personas, hypothetical representations of patients, can be used as an innovative strategy to support clinicians' use of PROMs in their practice. These personas embody patients' life stories, making them a valuable tool for understanding the person when using PROMs. The aim of this project focused on cancer-related experiences to develop personas as a knowledge translation strategy to support clinicians' use of PROMs for person-centred cancer care. METHODS: Eight older adults participated in online workshops (n = 2-3 participants/workshop; 1.5-hour sessions) to co-develop personas that reflected their collective experiences at a particular stage of their cancer journeys. Participants were asked to identify themes that focused on what the personas were thinking and feeling, what influenced how the personas acted, and the personas' overall goals. Participants subsequently completed an emotional well-being PROM from the perspective of the persona. Personas were further refined based on key themes identified during the workshop discussions. RESULTS: Four personas representing the cumulative experiences of the workshop participants were developed to help clinicians link PROM responses to patient stories. These personas became the basis of four practice scenarios, which were examples of interactions between a clinician and each persona, to demonstrate the use of PROMs in practice. CONCLUSION: Personas can be used to illustrate patients' life stories and contextualize PROMs data. As a knowledge translation strategy, personas can foster clinician awareness of how responses to PROMs can be used to initiate conversations to better understand patients' unique life situations.

Cancer Patients' Experiences with Telehealth before and during the COVID-19 Pandemic in British Columbia.

BACKGROUND: Patients have had their cancer care either postponed or changed to telehealth visits to reduce exposure to COVID-19. However, it is unclear how these changes may have affected their experiences. We aim to identify patient characteristics that affect telehealth experiences and evaluate their preferences for using telehealth in the future. METHODS: Patients who completed the Outpatient Cancer Care (OCC) Patient Experience Survey were invited to participate. They comepleted the modified OCC Survey, which focused on telehealth during the pandemic. Linear and logistic regression analyses were used to identify patient characteristics that influenced telehealth experiences and preferences for future telehealth use. RESULTS: Perceived ease of participation in telehealth is a significant predictor of the change in patients' ratings of their telehealth experience. We found that cancer patients had lower preferences for using telehealth in the future if they were older, female, or non-white; resided in an urban area; had no previous telehealth experience; had lower education; and had poorer mental health. CONCLUSIONS: To optimize cancer care and improve equitable access to high-quality telehealth care during the pandemic and beyond, clinicians and policymakers will need to consider patients' self-reported experiences and their personal characteristics.