Human left ventricular cardiac fibroblasts undergo a dynamic shift in secretome and gene expression toward a cardiac myofibroblast phenotype during early passage in typical culture expansion conditions.

Cardiac fibroblasts (CFs) are critical components of the cardiac niche and primarily responsible for assembly and maintenance of the cardiac extracellular matrix (ECM). CFs are increasingly of interest for tissue engineering and drug development applications, as they provide synergistic support to cardiomyocytes through direct cell-to-cell signaling and cell-to-ECM interactions via soluble factors, including cytokines, growth factors and extracellular vesicles. CFs can be activated to a cardiac myofibroblast (CMF) phenotype upon injury or stimulation with transforming growth factor beta 1. Once activated, CMFs assemble collagen-rich ECM, which is vitally important to stabilize scar formation following myocardial infarction, for example. Although there is greater experience with culture expansion of CFs among non-human strains, very little is known about human CF-to-CMF transitions and expression patterns during culture expansion. In this study, we evaluated for shifts in inflammatory and angiogenic expression profiles of human CFs in typical culture expansion conditions. Understanding shifts in cellular expression patterns during CF culture expansion is critically important to establish quality benchmarks and optimize large-scale manufacturing for future clinical applications.

Improving Family Presence in Long-Term Care during the COVID-19 Pandemic.

Family caregivers play a vital role in supporting the physical and mental health of long-term care (LTC) residents. Due to LTC visitor restrictions during the COVID-19 pandemic, residents (as well as family caregivers) showed significant adverse health outcomes due to a lack of family presence. To respond to these outcomes, eight implementation science teams led research projects in conjunction with Canadian LTC homes to promote the implementation of interventions to improve family presence. Overall, technological and virtual innovations, increased funding to the sector and partnerships with family caregivers were deemed effective methods to promote stronger family presence within LTC.

Defining cytotoxic drugs - you know it when you see it?

Safe handling precautions are an important measure used to prevent occupational exposure to hazardous antineoplastic drugs. Historically, the terms 'antineoplastic', 'chemotherapy' and 'cytotoxic' are frequently conflated. However, many current antineoplastic drugs do not have cytotoxic mechanisms of actions, leading to confusion when developing safe handling policies. Based on the mechanistic criteria outlined in this review, we have compiled a list of the most commonly used antineoplastic drugs with their cytotoxic or non-cytotoxic designations. We propose that this list can be used when discussing drug-specific safe handling precaution measures.

Community pharmacists as catalysts for deprescribing: An exploratory study using quality improvement processes.

BACKGROUND: There is growing international emphasis on deprescribing, involving the monitored reduction or stopping of medications that are no longer needed or that cause more harm than benefits, especially for the elderly. Community pharmacists are well positioned to partner with patients and their other health care providers in facilitating deprescribing activities. OBJECTIVE: To build community pharmacists' capacity to integrate deprescribing into their daily practices through training and workflow strategies. METHODS: This study used an exploratory mixed-methods (primarily qualitative) design. Staff at 4 Ontario pharmacies were trained to use deprescribing guidelines. Qualitative data were collected through field observations, notes from advisory group meetings and documented Plan-Do-Study-Act (PDSA) plans. Quantitative data were derived from process and output measures reported by the pharmacies. Iterative PDSA cycles allowed the project team to appraise and accelerate process improvements over time and to summarize findings on facilitators, barriers and the adaptation of processes. RESULTS: All 4 pharmacies identified individual and common goals related to deprescribing; however, drugs targeted and use of professional services to identify and address deprescribing opportunities varied. Each demonstrated that deprescribing activities could be integrated into daily practice and workflow. Common themes characterized approaches taken by each pharmacy: (1) processes used for capacity building among staff to identify patients for possible deprescribing, (2) approaches for preliminary interactions with patients, (3) in-depth medication reviews and (4) follow-up and monitoring. Approaches changed over time. CONCLUSION: Deprescribing appears to be feasible in community pharmacies. Data derived to populate a business model canvas informs the development of an in-depth business model for deprescribing. Can Pharm J (Ott) 2019;152:xx-xx.

Health and Community-Based Services for Individuals with Neurological Conditions.

BACKGROUND: The current study involves a national survey of healthcare providers who offer services for individuals with a variety of neurological conditions. It aims to describe the provision of health and community-based services as well as the admission criteria, waitlist practices, and referral sources of these services. METHODS: An online survey was directed at administrators/managers from publicly funded hospital programs, long-term care homes, and community-based healthcare provider agencies that were believed to be providing information and/or services to patients with a variety of neurological conditions. RESULTS: Approximately 60% (n=254) of respondents reported providing services in either urban/suburban areas or rural/remote areas only, whereas the remaining 40% (n=172) provided services regardless of patient location. A small proportion of respondents reported providing services for individuals with dystonia (28%), Tourette syndrome (17%), and Rett syndrome (13%). There was also a paucity of diverse healthcare professionals across all institutions, but particularly mental healthcare professionals in hospitals. Lastly, the majority of respondents reported numerous exclusion criteria with regard to service provision, including prevalent comorbid conditions. CONCLUSIONS: If the few services provided for these neurological patient populations exclude common comorbidities, it is likely that there will be no other place for these individuals to seek care.

Communities of practice for supporting health systems change: a missed opportunity.

BACKGROUND: Communities of practice (CoPs) have been used in the health sector to support professional practice change. However, little is known about how CoPs might be used to influence a system that requires change at and across various levels (i.e. front line care, organizational, governmental). In this paper we examine the experience of a CoP in the Canadian province of Ontario as it engages in improving the care of seniors. Our aim is to shed light on using CoPs to facilitate systems change. METHODS: This paper draws on year one findings of a larger multiple case study that is aiming to increase understanding of knowledge translation processes mobilized through CoPs. In this paper we strategically report on one case to illustrate a critical example of a CoP trying to effect systems change. Primary data included semi-structured interviews with CoP members (n = 8), field notes from five planning meetings, and relevant background documents. Data analysis included deductive coding (i.e. pre-determined codes aligned with the larger project) and inductive coding which allowed codes and themes to emerge. A thorough description of the case was prepared using all the coded data. RESULTS: The CoP recognized a need to support health professionals (nurses, dentists) and related paraprofessionals with knowledge, experience, and resources to appropriately address their clients' oral health care needs. Accordingly, the CoP led a knowledge-to-action initiative that involved a seven-part webinar series meant to transfer step-by-step, skill-based knowledge through live and archived webinars. Although the core planning team functioned effectively to develop the webinars, the CoP was challenged by organizational and long-term care sector cultures, as well as governmental structures within the broader health context. CONCLUSION: The provincial CoP functioned as an incubator that brought together best practices, research, experiences, a reflective learning cycle, and passionate champions. Nevertheless, the CoP's efforts to stimulate practice changes were met with broader resistance. Research about how to use CoPs to influence health systems change is needed given that CoPs are being tasked with this goal.

Development of a Chronic Care Model for Neurological Conditions (CCM-NC).

BACKGROUND: Persons with neurological conditions and their families face a number of challenges with the provision of health and community-based services. The purpose of this study was to understand the existing health and community service needs and gaps in care and to use this information to develop a model to specify factors and processes that may improve the quality of care and health and well-being for persons with neurological conditions. METHODS: We conducted semi-structured interviews with health care professionals, community-based non-health care professionals working with individuals with neurological conditions, and policy makers -from the Ministries of Health, Community and Social Services, Transportation and Education- across Canada. We used a purposive sampling and snowballing approach to obtain maximum variation across professions, sector and geography (provinces and territories, rural and urban). Data analysis was an iterative, constant comparative process involving descriptive and interpretive analyses and was initially guided by the components of the Expanded Chronic Care Model. RESULTS: A total of 180 individuals completed the interviews: 39% (n = 70) health care professionals, 47% (n = 85) community-based non-health care professionals, and 14% (n = 25) policy makers. Based on the data we developed the Chronic Care Model for Neurological Conditions (CCM-NC). The major needs/gaps are represented by the following themes: acceptance and openness to neurological conditions, evidence informed policy, investments and funding, supported transitions, caregiver support, and life enhancing resources (education, employment, housing and transportation), knowledge and awareness of neurological conditions and availability and access to health services. The model maintains that intersectoral collaboration across the health system, community and policy components is needed. It recognizes that attitudes, policies, enhanced community integration and health system changes are needed to develop activated patients and families, proactive service delivery teams, a person-centred health system and healthy public policy for persons with neurological conditions. CONCLUSION: The CCM-NC will generate debate and discussion about the actions needed in each of the model components to enable people with neurological conditions to sustain healthier lives. Next steps include validating the model with persons with neurological conditions, in and outside of the Canadian context and developing and evaluating interventions to test the model.

From Compliance to Care: Qualitative Findings from a Survey of Essential Caregivers in Ontario Long-Term Care Homes.

BACKGROUND: The COVID-19 pandemic highlighted the importance of the care provided by family members and close friends to older people living in long-term care (LTC) homes. Our implementation science team helped three Ontario LTC homes to implement an intervention to allow family members to enter the homes during pandemic lockdowns. OBJECTIVE: We used a variety of methods to support the implementation, and this paper reports results from an Ontario-wide survey intended to help us understand the nature of the care provided by family caregivers. METHODS: We administered a survey of essential caregivers in Ontario, and a single open-ended question yielded a substantial qualitative data set that we analysed with a coding and theming procedure that yielded 13 themes. FINDINGS: The 13 themes reveal deficiencies in Ontario's LTC sector, attempts to cope with the deficiencies, and efforts to influence change and improvement. DISCUSSION: Our findings indicate that essential caregivers find it necessary to take on vital roles in order to shore up two significant gaps in the current system: they provide psychosocial and emotional (and sometimes even basic) care to residents, and they play a monitoring and advocacy role to compensate for the failings of the current regulatory compliance regime.

Minimal impacts of invasive Scaevola taccada on Scaevola plumieri via pollinator competition in Puerto Rico.

Introduction: Scaevola taccada and Scaevola plumieri co-occur on shorelines of the Caribbean. Scaevola taccada is introduced in this habitat and directly competes with native dune vegetation, including S. plumieri, a species listed as locally endangered and threatened in Caribbean locations. This study addresses whether the invasive S. taccada also impacts the native S. plumieri indirectly by competing for pollinators and represents the first comparative study of insect visitation between these species. Methods: Insect visitation rates were measured at sites where species co-occur and where only the native occurs. Where species cooccur, insect visitors were captured, identified and analyzed for the pollen they carry. Pollen found on open-pollinated flowers was analyzed to assess pollen movement between the two species. We also compared floral nectar from each species by measuring volume, sugar content, and presence and proportions of amine group containing constituents (AGCCs). Results: Our results demonstrate that both species share insect visitors providing the context for possible pollinator competition, yet significant differences in visitation frequency were not found. We found evidence of asymmetrical heterospecific pollen deposition in the native species, suggesting a possible reproductive impact. Insect visitation rates for the native were not significantly different between invaded and uninvaded sites, suggesting that the invasive S. taccada does not limit pollinator visits to S. plumieri. Comparisons of nectar rewards from the invasive and the native reveal similar volumes and sugar concentrations, but significant differences in some amine group containing constituents that may enhance pollinator attraction. Conclusion: Our analysis finds no evidence for pollination competition and therefore S. taccada's main impacts on S. plumieri are through competitive displacement and possibly through reproductive impacts as a consequence of heterospecific pollen deposition.

Human iPSC-derived Committed Cardiac Progenitors Generate Cardiac Tissue Grafts in a Swine Ischemic Cardiomyopathy Model without Triggering Ventricular Arrhythmias.

BACKGROUND: The adult human heart following a large myocardial infarction is unable to regenerate heart muscle and instead forms scar with the risk of progressive heart failure. Large animal studies have shown that intramyocardial injection of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) following a myocardial infarction result in cell grafts but also ventricular arrhythmias. We hypothesized that intramyocardial injection of committed cardiac progenitor cells (CCPs) derived from iPSCs, combined with cardiac fibroblast-derived extracellular matrix (cECM) to enhance cell retention will: i) form cardiomyocyte containing functional grafts, ii) be free of ventricular arrhythmias and iii) restore left ventricular contractility in a post-myocardial infarction (MI) cardiomyopathy swine model. METHODS: hiPSCs were differentiated using bioreactors and small molecules to produce a population of committed cardiac progenitor cells (CCPs). MI was created using a coronary artery balloon occlusion and reperfusion model in Yucatan mini pigs. Four weeks later, epicardial needle injections of CCPs+cECM were performed in a small initial feasibility cohort, and then transendocardial injections (TEI) of CCPs+cECM, CCPs alone, cECM alone or vehicle control into the peri-infarct region in a larger randomized cohort. A 4-drug immunosuppression regimen was administered to prevent rejection of human CCPs. Arrhythmias were evaluated using implanted event recorders. Magnetic resonance imaging (MRI) and invasive pressure volume assessment were used to evaluate left ventricular anatomic and functional performance, including viability. Detailed histology was performed on the heart to detect human grafts. RESULTS: A scalable biomanufacturing protocol was developed generating CCPs which can efficiently differentiate to cardiomyocytes or endothelial cells in vitro. Intramyocardial delivery of CCPs to post-MI porcine hearts resulted in engraftment and differentiation of CCPs to form ventricular cardiomyocyte rich grafts. There was no significant difference in cardiac MRI-based measured cardiac volumes or function between control, CCP and CCP+cECM groups; however, dobutamine stimulated functional reserve was improved in CCP and CCP+cECM groups. TEI delivery of CCPs with or without cECM did not result in tumors or trigger ventricular arrhythmias. CONCLUSIONS: CCPs are a promising cell source for post-MI heart repair using clinically relevant TEI with a low risk of engraftment ventricular arrhythmias.

A Community of Practice on Environmental Design for Long-Term Care Residents with Dementia.

The use of communities of practice (CoP) to support the application of knowledge in improved geriatric care practice is not widely understood. This case study's aim was to gain a deeper understanding of the knowledge-to-action (KTA) processes of a CoP focused on environmental design, to improve how persons with dementia find their way around in long-term care (LTC) homes. Qualitative data were collected (key informant interviews, observations, and document review), and analysed using emergent coding. CoP members contributed extensive knowledge to the KTA process characterized by the following themes: team dynamics, employing a structured process, technology use, varied forms of knowledge, and a clear initiative. The study's CoP effectively synthesized and translated knowledge into practical tools to inform changes in practice, programs, and policy on dementia care. More research is needed on how to involve patients and caregivers in the KTA processes, and to ensure that practical application of knowledge has financial and policy support.

The use of tumour volumetrics to assess response to therapy in anticancer clinical trials.

Serial evaluations of tumour burden using imaging, mainly computed tomography and magnetic resonance imaging, form the basis for assessing treatment response in many clinical trials of anticancer therapeutics. Traditionally, these evaluations have been based on linear measurements of tumour size. Such measurements have limitations related to variability in technical factors, tumour morphology and reader decisions. Measurements of entire tumour volumes may overcome some of the limitations of linear tumour measurements, improving our ability to detect small changes reliably and increasing statistical power per subject in a trial. Certain technical factors are known to affect the accuracy and precision of volume measurements, and work is in progress to define these factors more thoroughly and to qualify tumour volume as a biomarker for the purposes of drug development.

Guidance to (Re)integrate Caregivers as Essential Care Partners Into the LTC Setting: A Rapid Review.

OBJECTIVES: This rapid review aimed to identify the strategies used to (re)integrate essential caregivers (ECs) into the LTC setting, particularly pertaining to principles of equity, diversity, and inclusion. In addition, this rapid review aimed to identify the strategies used during prior infectious disease threats, when similar blanket visitor restrictions were implemented in LTC homes. The review was part of a larger effort to support LTC homes in Ontario. DESIGN: A rapid review was conducted in accordance with principles from the Canadian National Collaborating Centre for Methods and Tools. SETTING AND PARTICIPANTS: ECs, residents, staff, and policy decision makers in long-term care home settings. METHODS: Five electronic databases were searched for academic and gray literature using predefined search terms. Selected documents met inclusion criteria if they included policy guidance or an intervention to (re)integrate ECs into LTC homes at the local, national, and/or international level. RESULTS: In total, 15 documents met the inclusion and exclusion criteria. All documents retrieved focused on the context of COVID-19. Documents were either policy guidance (n = 13) or primary research studies (n = 2). Documents differed in these notable ways: Definition of EC; the degree to which an EC is recognized for her or his role in the care of the resident; the degree to which ECs are (re)integrated into the LTC setting is prioritized; response to community spread of COVID-19; visitation during an outbreak or if a resident is symptomatic; the reliance on equity, diversity, and inclusion principles; and lastly, monitoring and improving the process. CONCLUSIONS AND IMPLICATIONS: Using an equity, diversity, and inclusion lens, we posit promising practices for (re)integration. It is clear from the rapid review that more research is needed to understand the efficacy of policies and guidelines to (re)integrate ECs into the LTC setting. Until such evidence is available, expert opinion will drive best care practices.

Quantitative imaging test approval and biomarker qualification: interrelated but distinct activities.

UNLABELLED: Quantitative imaging biomarkers could speed the development of new treatments for unmet medical needs and improve routine clinical care. However, it is not clear how the various regulatory and nonregulatory (eg, reimbursement) processes (often referred to as pathways) relate, nor is it clear which data need to be collected to support these different pathways most efficiently, given the time- and cost-intensive nature of doing so. The purpose of this article is to describe current thinking regarding these pathways emerging from diverse stakeholders interested and active in the definition, validation, and qualification of quantitative imaging biomarkers and to propose processes to facilitate the development and use of quantitative imaging biomarkers. A flexible framework is described that may be adapted for each imaging application, providing mechanisms that can be used to develop, assess, and evaluate relevant biomarkers. From this framework, processes can be mapped that would be applicable to both imaging product development and to quantitative imaging biomarker development aimed at increasing the effectiveness and availability of quantitative imaging. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100800/-/DC1.

eLearning, knowledge brokering, and nursing: strengthening collaborative practice in long-term care.

Interprofessional collaboration is vital to the delivery of quality care in long-term care settings; however, caregivers in long-term care face barriers to participating in training programs to improve collaborative practices. Consequently, eLearning can be used to create an environment that combines convenient, individual learning with collaborative experiential learning. Findings of this study revealed that learners enjoyed the flexibility of the Working Together learning resource. They acquired new knowledge and skills that they were able to use in their practice setting to achieve higher levels of collaborative practice. Nurses were identified as team leaders because of their pivotal role in the long-term care home and collaboration with all patient care providers. Nurses are ideal as knowledge brokers for the collaborative practice team. Quantitative findings showed no change in learner's attitudes regarding collaborative practice; however, interviews provided examples of positive changes experienced. Face-to-face collaboration was found to be a challenge, and changes to organizations, systems, and technology need to be made to facilitate this process. The Working Together learning resource is an important first step toward strengthening collaboration in long-term care, and the pilot implementation provides insights that further our understanding of both interprofessional collaboration and effective eLearning.

Implementing deprescribing guidelines into frontline practice: Barriers and facilitators.

A Bruyère Evidence-Based Deprescribing Guideline Symposium was held in March 2018; one component focused on implementing deprescribing guidelines into practice. An interactive discussion activity allowed the 107 participants to share experiences and ideas concerning the barriers and facilitators that arise when moving deprescribing guidelines into frontline practice. Participants identified 8 broad challenges and problem areas. These included challenges and barriers that arise in the daily practices of pharmacists and prescribers and in other health care settings, and those related to existing policies, processes, and financial structures. They also identified 10 factors that facilitated implementation efforts, including: educating patients, caregivers, health care providers (HCPs) and staff; improving collaboration across practice disciplines; expanding the evidence for deprescribing; and fostering organizational cultures of deprescribing. The results indicate that participants are committed to deprescribing and are moving forward with efforts to bring about change. Participants recognize that the implementation of deprescribing is best conceived of as a comprehensive systems change, and that patients and the public need to be involved in deprescribing processes and activities.

Deprescribing guidelines: An international symposium on development, implementation, research and health professional education.

Deprescribing is a clinically important and feasible innovation that ensures medication efficacy, reduces harms, and mitigates polypharmacy. It involves reducing doses or stopping medications that are not useful, no longer needed, or which may be causing harm. It may also involve changing to a safer agent or using non-pharmacological approaches for care instead. Clinical guidelines combined with behaviour changes (of health care providers (HCPs), the public, and health care decision-makers) are needed to integrate deprescribing into routine practice. Using rigorous international standards, the Bruyère Research Institute Deprescribing Guidelines research team validated a ground-breaking deprescribing guideline methodology and developed or co-developed 5 evidence-based deprescribing guidelines. In March 2018, the team hosted an international symposium convening HCPs, researchers, public agencies, policymakers, and patient advocates in Ottawa, Ontario, Canada. This 3-day symposium aimed to facilitate knowledge exchange amongst guideline developers, users, and the public; initiate partnerships and collaborations for new deprescribing guideline recommendations and effectiveness research; and to continue work on HCP deprescribing education activities. An interprofessional planning committee developed an overall agenda, and small groups worked on session objectives and formats for different components: methods for rigorous deprescribing guideline development, implementation experiences, research/evaluation experiences and educational needs. Through a series of keynote speakers, panel discussions, and small working groups, the symposium provided a forum for participants to meet one another, learn about their different experiences with deprescribing guidelines, and develop collaborations for future initiatives. One hundred thirty participants, from 10 countries and representing over 100 institutions and organizations took part. Symposium proceedings are presented in this issue of RSAP for sharing with the wider community engaged in the care of patients with problematic polypharmacy.