Supporting researchers in knowledge translation and dissemination of their research to increase usability and impact.

PURPOSE: One of the key areas of delivery of the 'Action Plan for Health Research 2019-2029', for the Health Service Executive (HSE) in Ireland, is adding value and using data and knowledge, including health-related quality of life (HRQoL), for improved health care, service delivery and better population health and wellbeing. The development of governance, management and support framework and mechanisms will provide a structure for ensuring research is relevant to the organisation's service plan, well designed, has a clear plan for dissemination and translation of knowledge, and minimises research waste. Developing a process for the translation, dissemination and impact of research is part of the approach to improving translation of research into practice and aligning it with knowledge gaps. A project was undertaken to develop a clear, unified, universally applicable approach for the translation, dissemination, and impact of research undertaken by HSE staff and commissioned, sponsored, or hosted by the organisation. This included the development of guidance, training, and information for researchers. METHODS: Through an iterative process, an interdisciplinary working group of experts in knowledge translation (KT), implementation science, quality improvement and research management, identified KT frameworks and tools to form a KT, dissemination, and impact process for the HSE. This involved a literature review, screening of 247 KT theories, models, and frameworks (TMFs), review of 18 TMFs selected as usable and applicable to the HSE, selection of 11 for further review, and final review of 6 TMFs in a consensus workshop. An anonymous online survey of HSE researchers, consisting of a mixture of multiple choice and free text questions, was undertaken to inform the development of the guidance and training. RESULTS: A pilot of the KT process and guidance, involving HSE researchers testing its use at various stages of their research, demonstrated the need to guide researchers through planning, stakeholder engagement, and disseminating research knowledge, and provide information that could easily be understood by novice as well as more experienced researchers. A survey of all active researchers across the organisation identified their support and knowledge requirements and led to the development of accompanying guidance to support researchers in the use of the process. Researchers of all levels reported that they struggled to engage with stakeholders, including evidence users and policy makers, to optimise the impact of their research. They wanted tools that would support better engagement and maximise the value of KT. As a result of the project a range of information, guidance, and training resources have been developed. CONCLUSION: KT is a complex area and researchers need support to ensure they maximise the value of their research. The KT process outlined enables the distilling of a clear message, provides a process to engage with stakeholders, create a plan to incorporate local and political context, and can show a means to evaluate how much the findings are applied in practice. This is a beneficial application of KT in the field of patient reported outcomes. In implementing this work, we have reinforced the message that stakeholder engagement is crucial from the start of the research study and increases engagement in, and ownership of, the research knowledge.

The usability and applicability of knowledge translation theories, models, and frameworks for research in the context of a national health service.

BACKGROUND: Translating research findings into service improvements for patients and/or policy changes is a key challenge for health service organizations. The Health Service Executive (HSE) in Ireland launched the Action Plan for Health Research 2019-2029, as reported by Terrés (HSE, Dublin, 2019), one of the goals of which is to maximize the impact of the research that takes place within the service to achieve improvements in patient care, services, or policy change. The purpose of this research is to review the literature on knowledge translation theories, models, and frameworks (TMFs) and to assess the suitability of the TMFs for HSE use, selecting one or more for this purpose. The aim is to produce guidance for HSE researchers and other health services staff, validate the usability of the framework(s) with researchers, and review and implement the guidance. It was hoped that identifying a suitable methodology would provide the means to increase the uptake and application of research findings, and reduce research wastage. This paper reports on the first part of the study: the review, assessment, and selection of knowledge translation TMFs for a national health service. METHODS: An interdisciplinary working group of academic experts in implementation science, research wastage, and knowledge translation, along with key representatives from research funders (Health Research Board) and HSE personnel with expertise in quality improvement and research management, undertook a three-stage review and selection process to identify a knowledge translation TMF that would be suitable and usable for HSE purposes. The process included a literature review, consensus exercise, and a final consensus workshop. The review group adopted the Theory Comparison and Selection Tool (T-CaST) developed by Birken et al. (Implement Sci 13: 143, 2018) to review knowledge translation theories, models, and frameworks. RESULTS: From 247 knowledge translation TMFs initially identified, the first stage of the review identified 18 that met the criteria of validity, applicability, relevance, usability, and ability to be operationalized in the local context. A further review by a subgroup of the working group reduced this number to 11. A whole-group review selected six of these to be reviewed at a facilitated consensus workshop, which identified three that were suitable and applicable for HSE use. These were able to be mapped onto the four components of the HSE knowledge translation process: knowledge creation, knowledge into action, transfer and exchange of knowledge, and implementation and sustainability. CONCLUSION: The multiplicity of knowledge translation TMFs presents a challenge for health service researchers in making decisions about the appropriate methods for disseminating their research. Building a culture that uses research knowledge and evidence is important for organizations seeking to maximize the benefits from research. Supporting researchers with guidance on how to disseminate and translate their research can increase the uptake and application of research findings. The use of robust selection criteria enabled the HSE to select relevant TMFs and develop a process for increasing the dissemination and translation of research knowledge. The guidance developed to inform and educate researchers and knowledge users is expected to increase organizational capacity to promote a culture of research knowledge and evidence use within the HSE.

Proteomic and functional characterization of the outer membrane vesicles from the gastric pathogen Helicobacter pylori.

The gastric pathogen Helicobacter pylori causes a spectrum of gastro-duodenal diseases, which may be mediated in part by the outer membrane vesicles (OMVs) constitutively shed by the pathogen. We aimed to determine the proteome of H. pylori OMV to help evaluate the mechanisms whereby these structures confer their known immuno-modulatory and cytotoxic activities to host cells, as such disease-associated activities are also conferred by the bacterium from which the vesicles are derived. We also evaluated the effect of the OMV on gastric/colonic epithelial cells, duodenal explants and neutrophils. A proteomic analysis of the OMV proteins separated by SDS-PAGE from two strains of H. pylori (J99 and NCTC 11637) was undertaken and 162 OMV-associated proteins were identified in J99 and 91 in NCTC 11637 by LC-MS/MS. The vesicles are rich in membrane proteins, porins, adhesins and several molecules known to modulate chemokine secretion, cell proliferation and other host cellular processes. Further, the OMVs are also vehicles for the carriage of the cytotoxin-associated gene A cytotoxin in addition to the previously documented toxin, vacuolating cytotoxin. Taken together, it is evident from the proteome of H. pylori OMV that these structures are equipped with the molecules required to interact with host cells in a manner not dissimilar from the intact pathogen.

Helicobacter pylori extract induces nuclear factor-kappa B, activator protein-1, and cyclooxygenase-2 in esophageal epithelial cells.

Helicobacter pylori infection is recognized as the major cause of gastritis and gastric cancer; however, its role in the development of gastroesophageal reflux disease and Barrett's adenocarcinoma is unclear. The expression of NF-kappaB, AP-1, and COX-2 may be important in inflammation and tumorigenesis in the esophagus. The aim of this study was to examine the effect of live H pylori or H pylori extract (HPE) on these factors in the esophageal epithelial cell lines SKGT-4 and OE33. NF-kappaB and AP-1 activity were assessed by gel shift assay and COX-2 by Western blotting. Coculture of SKGT-4 and OE33 with live H pylori and HPE induced NF-kappaB and AP-1 DNA-binding activity, and also decreased IkappaB-alpha levels. Treatment with the specific MEK1/2 MAPK inhibitor PD98059, but not the p38 MAPK inhibitor SB203580, inhibited NF-kappaB and AP-1 activity. The antioxidant vitamin C inhibited H pylori-induced NF-kappaB activation, but increased AP-1 expression. Moreover, HPE induced COX-2 expression and IL-8 production, and PD98059 inhibited COX-2 expression, ERK1/2 phosphorylation, and IL-8 production. These data demonstrate that both live H pylori and HPE induce NF-kappaB and AP-1 expression in esophageal epithelial cells. The induction of such transcription factors may play a role in the specific immune response within Barrett's mucosa and may indirectly cause inflammation of the gastric cardia and the distal esophagus.