RESUMEN
Several of our internal organs, including heart, lungs, stomach, and spleen, develop asymmetrically along the left-right (LR) body axis. Errors in establishing LR asymmetry, or laterality, of internal organs during early embryonic development can result in birth defects. In several vertebrates-including humans, mice, frogs, and fish-cilia play a central role in establishing organ laterality. Motile cilia in a transient embryonic structure called the "left-right organizer" (LRO) generate a directional fluid flow that has been proposed to be detected by mechanosensory cilia to trigger asymmetric signaling pathways that orient the LR axis. However, the mechanisms that control the form and function of the ciliated LRO remain poorly understood. In the zebrafish embryo, precursor cells called dorsal forerunner cells (DFCs) develop into a transient ciliated structure called Kupffer's vesicle (KV) that functions as the LRO. DFCs can be visualized and tracked in the embryo, thereby providing an opportunity to investigate mechanisms that control LRO development. Previous work revealed that proliferation of DFCs via mitosis is a critical step for developing a functional KV. Here, we conducted a targeted pharmacological screen to identify mechanisms that control DFC proliferation. Small molecule inhibitors of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) were found to reduce DFC mitosis. The SERCA pump is involved in regulating intracellular calcium ion (Ca2+) concentration. To visualize Ca2+ in living embryos, we generated transgenic zebrafish using the fluorescent Ca2+ biosensor GCaMP6f. Live imaging identified dynamic cytoplasmic Ca2+ transients ("flux") that occur unambiguously in DFCs. In addition, we report Ca2+ flux events that occur in the nucleus of DFCs. Nuclear Ca2+ flux occurred in DFCs that were about to undergo mitosis. We find that SERCA inhibitor treatments during DFC proliferation stages alters Ca2+ dynamics, reduces the number of ciliated cells in KV, and alters embryo laterality. Mechanistically, SERCA inhibitor treatments eliminated both cytoplasmic and nuclear Ca2+ flux events, and reduced progression of DFCs through the S/G2 phases of the cell cycle. These results identify SERCA-mediated Ca2+ signaling as a mitotic regulator of the precursor cells that give rise to the ciliated LRO.
RESUMEN
BACKGROUND: Asthma is a chronic respiratory disease that poses a substantial burden on individuals and the health care system. Despite published national guidelines for the diagnosis and management of asthma, considerable care gaps exist. Suboptimal adherence to asthma diagnosis and management guidelines contributes to poor patient outcomes. The integration of electronic tools (eTools) into electronic medical records (EMRs) represents a knowledge translation opportunity to support best practices. OBJECTIVE: The purpose of this study was to determine how best to integrate evidence-based asthma eTools into primary care EMRs across Ontario and Canada to improve adherence to guidelines as well as measure and monitor performance. METHODS: In total, 2 focus groups comprising physicians and allied health professionals who were considered experts in primary care, asthma, and EMRs were convened. One focus group also included a patient participant. Focus groups used a semistructured discussion-based format to consider the optimal methods for integrating asthma eTools into EMRs. Discussions were held on the web via Microsoft Teams (Microsoft Corp). The first focus group discussed integrating asthma indicators into EMRs using eTools, and participants completed a questionnaire evaluating the clarity, relevance, and feasibility of collecting asthma performance indicator data at the point of care. The second focus group addressed how to incorporate eTools for asthma into a primary care setting and included a questionnaire evaluating the perceived utility of various eTools. Focus group discussions were recorded and analyzed using thematic qualitative analysis. The responses to focus group questionnaires were assessed using descriptive quantitative analysis. RESULTS: Qualitative analysis of the 2 focus group discussions revealed 7 key themes: designing outcome-oriented tools, gaining stakeholder trust, facilitating open lines of communication, prioritizing the end user, striving for efficiency, ensuring adaptability, and developing within existing workflows. In addition, 24 asthma indicators were rated according to clarity, relevance, feasibility, and overall usefulness. In total, 5 asthma performance indicators were identified as the most relevant. These included smoking cessation support, monitoring using objective measures, the number of emergency department visits and hospitalizations, assessment of asthma control, and presence of an asthma action plan. The eTool questionnaire responses revealed that the Asthma Action Plan Wizard and Electronic Asthma Quality of Life Questionnaire were perceived to be the most useful in primary care. CONCLUSIONS: Primary care physicians, allied health professionals, and patients consider that eTools for asthma care present a unique opportunity to improve adherence to best-practice guidelines in primary care and collect performance indicators. The strategies and themes identified in this study can be leveraged to overcome barriers associated with asthma eTool integration into primary care EMRs. The most beneficial indicators and eTools, along with the key themes identified, will guide future asthma eTool implementation.
RESUMEN
BACKGROUND: Viable knowledge translation (KT) strategies are increasingly sought to improve asthma diagnosis, particularly in primary care. Despite this understanding, practical KT tools to support primary care practitioners are not widely available. Electronic medical records (EMRs) offer an opportunity to optimize the diagnosis and surveillance of chronic diseases such as asthma, and support quality improvement initiatives that increase adherence to guideline-recommended care. This review aims to describe the current state of electronic KT electronic tools (eTools) and surveillance systems for asthma and identify opportunities to increase adherence to asthma diagnostic guidelines by implementing digital KT eTools. METHODS: Systematic literature searches were conducted on Ovid MEDLINE that included the search terms: asthma, asthma diagnosis, asthma surveillance, electronic health records, translational medical research, quality improvement, professional practice gaps, and primary health care published in the previous 10 years. In total, the searches returned 971 articles, 163 of which were considered relevant and read in full. An additional 28 articles were considered after reviewing the references from selected articles. 75 articles were included in this narrative review. RESULTS: Established KT eTools for asthma such as electronic questionnaires, computerized clinical decision support systems (CDSS), chronic disease surveillance networks, and asthma registries have been effective in improving the quality of asthma diagnosis and care. As well, chronic disease surveillance systems, severe asthma registries, and workplace asthma surveillance systems have demonstrated success in monitoring asthma outcomes. However, lack of use and/or documentation of objective measures of lung function, challenges in identifying asthma cases in EMRs, and limitations of data sources have created barriers in the development of KT eTools. Existing digital KT eTools that overcome these data quality limitations could provide an opportunity to improve adherence to best-practice guidelines for asthma diagnosis and management. CONCLUSION: Future initiatives in the development of KT eTools for asthma care should focus on strategies that assist healthcare providers in accurately diagnosing and documenting cases of asthma. A digital asthma surveillance system could support adherence to best-practice guidelines of asthma diagnosis and surveillance by prompting use of objective methods of confirmation to confirm an asthma diagnosis within the EMR.
RESUMEN
BACKGROUND: A work-related asthma (WRA) screening questionnaire is currently being validated for implementation in clinical settings. To minimize barriers to integrating tools into clinical practice, a discussion of strategies for the implementation of the questionnaire has begun. OBJECTIVE: This study aimed to understand the benefits, feasibility, barriers, and limitations of implementing the Work-related Asthma Screening Questionnaire-Long version (WRASQ[L]) and asthma e-tools in clinical settings and propose dissemination and implementation strategies for the WRASQ(L). METHODS: This study was conducted in Kingston, Ontario, Canada, from September 2019 to August 2021. A workshop and 2 questionnaires were used to understand the benefits of and barriers to implementing the questionnaire in clinical settings. An expert advisory committee was established to develop the implementation and dissemination strategies. Workshops were semistructured and used thematic qualitative analysis to identify themes that provided an understanding of the benefits and limitations of and barriers to using the WRASQ(L), and e-tools in general, in clinical settings. Workshop participants included patients and health care providers, including physicians, nurses, and asthma educators, who were implementation specialists and expert electronic medical record users. A questionnaire focusing on providers' knowledge and awareness of WRA and another focusing on WRASQ(L) feedback was administered at the workshops. Advisory committee members from relevant stakeholders met 3 times to strategize implementation opportunities. RESULTS: A total of 6 themes were identified in the workshop: involving and addressing patient needs, novel data collection, knowledge translation, time considerations, functional and practical barriers, and human limitations. Questionnaire responses yielded positive feedback on the utility of the WRASQ(L) in clinical settings. All participants agreed that it is an easy way of collecting information on occupational and exposure history and could prompt a discussion between the health care provider and patient on how the workplace and exposures could affect one's asthma, increase awareness of WRA in patients and providers, and increase awareness of exposures in the workplace. Implementation and dissemination strategies were generated with input from the advisory committee. CONCLUSIONS: Stakeholders and workshop participants consider the WRASQ(L) to be a useful tool that satisfies many provider needs in their clinical settings. Once validated, dissemination strategies will include developing educational materials that include the WRASQ(L), linking the questionnaire to stakeholder websites or e-toolkits, translation into other languages, leveraging health care and research networks, conference presentations, and peer-reviewed publications. Implementation strategies will include integration into electronic medical records; designing multifaceted interventions; and targeting nontraditional settings such as workplaces, pharmacies, and research settings. The WRASQ(L) addresses many benefits of and barriers to implementation, as identified in the workshop themes. These themes will guide future implementation and dissemination strategies, noting that human limitations identified in providers and patients will need to be overcome for successful implementation.
RESUMEN
BACKGROUND: Work-related asthma (WRA) accounts for up to 25% of all adults with asthma. Early diagnosis is key for optimal management as delays in diagnosis are associated with worse outcomes. However, WRA is significantly underreported and the median time to diagnosis is 4 years. The objective of this review is to identify the gaps in awareness and reporting of WRA and identify gaps in current knowledge translation strategies for chronic disease in general, and asthma specifically. This will identify reasons for delays in WRA diagnosis, as well inform suggestions to improve knowledge translation strategies for dissemination and implementation of WRA prevention and management guidelines. METHODS: Non-systematic literature reviews were conducted on PubMed with a focus on work-related asthma screening and diagnosis, and knowledge translation or translational medicine research in asthma and chronic disease. In total, 3571 titles and abstracts were reviewed with no restriction on date published. Of those, 207 were relevant and fully read. Another 37 articles were included and reviewed after citation reviews of articles from the initial search and from suggestions from editors. In total, 63 articles were included in the final review. RESULTS: Patients, employers, and healthcare professionals lack awareness and under-report WRA which contribute to the delayed diagnosis of WRA, primarily through lack of education, stigma associated with WRA, and lack of awareness and screening in primary care. Knowledge translation strategies for asthma research typically involve the creation of guidelines for diagnosis of the disease, asthma care plans and tools for education and management. While there are some prevention programs in place for certain industries, gaps in knowledge translation strategies including lack of screening tools currently available for WRA, poor education of employers and physicians in identifying WRA, and education of patients is often done post-diagnosis and focuses on management rather than prevention or screening. CONCLUSION: Future knowledge translation strategies should focus on educating employees and employers well before potential exposure to agents associated with WRA and screening for WRA in primary care to enable health care providers to recognize and diagnose WRA.
