Improving the management of mild traumatic brain injury in the emergency department: factors influencing evidence uptake and designing a targeted, theory-informed intervention to improve practice and patient outcomes

Background - Despite the availability of evidence-based guidelines for the management of mild traumatic brain injury (mTBI) in the emergency department (ED), variations in practice exist. Implementation research can contribute to reducing these variations in practice by studying the determinants, processes and effects of implementation efforts and providing evidence about what works when designing, selecting and improving implementation interventions. The ED environment has unique characteristics that can have an impact on its responsiveness to change. An understanding of these factors influencing practice change is essential to develop an effective implementation intervention that is feasible and acceptable. There is limited research on how to develop targeted, theory-informed implementation interventions in this setting. Aims - The aim of this thesis is to describe the process of developing a targeted, theory-informed intervention to increase the uptake of evidence-based recommendations in the management of mTBI in the ED. Specifically to: 1) identify the key evidence-based recommendations to be implemented, 2) explore and identify the influencing factors (barriers and enablers) to change using relevant theoretical frameworks, 3) develop a targeted, theory-informed intervention by identifying intervention components to overcome these factors that is acceptable and feasible to deliver, and 4) describe the process of developing fidelity measures for intervention components. Methods - A systematic scoping review was conducted to assess the volume and scope of implementation research in the ED setting; a systematic review of clinical guidelines for the management of mTBI, followed by a formal stakeholder consultation process, to develop locally applicable evidence-based recommendations for implementation; qualitative interviews with ED clinicians were used to explore the professional and organisational factors influencing uptake of the recommended behaviours using two theoretical frameworks. A systematic, stepped approach was developed to identify and operationalise intervention components to address the influencing factors and was informed by theory, evidence and feasibility considerations. A review of process evaluations of similar tailored interventions to that developed in the thesis was used to inform development of fidelity measures. Results - The scoping review found a significant increase in the volume of implementation research, however most studies focused on identifying evidence-practice gaps or utilised weak study designs to evaluate the effects of implementation interventions. Four key evidence-based recommendations were identified to improve the management of mTBI in the ED. Interviews with 42 ED staff identified professional and organisational factors that influenced these recommendations and presented theoretically based targets for intervention components. The resulting five intervention components consisted of several behaviour change techniques (BCTs). Fidelity measures were developed for two of these intervention components. Conclusions - This thesis provides a systematic, theory- and evidence-informed approach to developing an intervention aiming to improve the management of mTBI in the ED. Theoretical frameworks, evidence-based BCTs, evidence about the effects of modes of delivery and feasibility information were systematically brought together to develop the intervention. Implementation research is a cumulative science and this intervention is currently being evaluated in a national cluster randomised controlled trial, adding to the evidence of the effectiveness of theory-informed interventions to improve clinical practice

Improving the management of mild traumatic brain injury in the emergency department: factors influencing evidence uptake and designing a targeted, theory-informed intervention to improve practice and patient outcomes

Background - Despite the availability of evidence-based guidelines for the management of mild traumatic brain injury (mTBI) in the emergency department (ED), variations in practice exist. Implementation research can contribute to reducing these variations in practice by studying the determinants, processes and effects of implementation efforts and providing evidence about what works when designing, selecting and improving implementation interventions. The ED environment has unique characteristics that can have an impact on its responsiveness to change. An understanding of these factors influencing practice change is essential to develop an effective implementation intervention that is feasible and acceptable. There is limited research on how to develop targeted, theory-informed implementation interventions in this setting. Aims - The aim of this thesis is to describe the process of developing a targeted, theory-informed intervention to increase the uptake of evidence-based recommendations in the management of mTBI in the ED. Specifically to: 1) identify the key evidence-based recommendations to be implemented, 2) explore and identify the influencing factors (barriers and enablers) to change using relevant theoretical frameworks, 3) develop a targeted, theory-informed intervention by identifying intervention components to overcome these factors that is acceptable and feasible to deliver, and 4) describe the process of developing fidelity measures for intervention components. Methods - A systematic scoping review was conducted to assess the volume and scope of implementation research in the ED setting; a systematic review of clinical guidelines for the management of mTBI, followed by a formal stakeholder consultation process, to develop locally applicable evidence-based recommendations for implementation; qualitative interviews with ED clinicians were used to explore the professional and organisational factors influencing uptake of the recommended behaviours using two theoretical frameworks. A systematic, stepped approach was developed to identify and operationalise intervention components to address the influencing factors and was informed by theory, evidence and feasibility considerations. A review of process evaluations of similar tailored interventions to that developed in the thesis was used to inform development of fidelity measures. Results - The scoping review found a significant increase in the volume of implementation research, however most studies focused on identifying evidence-practice gaps or utilised weak study designs to evaluate the effects of implementation interventions. Four key evidence-based recommendations were identified to improve the management of mTBI in the ED. Interviews with 42 ED staff identified professional and organisational factors that influenced these recommendations and presented theoretically based targets for intervention components. The resulting five intervention components consisted of several behaviour change techniques (BCTs). Fidelity measures were developed for two of these intervention components. Conclusions - This thesis provides a systematic, theory- and evidence-informed approach to developing an intervention aiming to improve the management of mTBI in the ED. Theoretical frameworks, evidence-based BCTs, evidence about the effects of modes of delivery and feasibility information were systematically brought together to develop the intervention. Implementation research is a cumulative science and this intervention is currently being evaluated in a national cluster randomised controlled trial, adding to the evidence of the effectiveness of theory-informed interventions to improve clinical practice

Loss of Cytochrome c Oxidase Promotes RAS-Dependent ROS Production from the ER Resident NADPH Oxidase, Yno1p, in Yeast.

Many disease states, including the aging process, are associated with the accumulation of mitochondria harboring respiratory dysfunction. Mitochondrial dysfunction is often accompanied by increased ROS levels that can contribute to cellular dysfunction and disease etiology. Here we use the model eukaryote S. cerevisiae to investigate whether reduced cytochrome c oxidase (COX) activity, commonly reported in aging organisms and associated with neurodegenerative disorders, leads to ROS production from mitochondria. We provide evidence that although reduced COX complex activity correlates with ROS accumulation, mitochondria are not the major production center. Instead we show that COX-deficient mitochondria activate Ras upon their outer membrane that establishes a pro-ROS accumulation environment by suppressing antioxidant defenses and the ERAD-mediated turnover of the ER-localized NADPH oxidase Yno1p. Our data suggest that dysfunctional mitochondria can serve as a signaling platform to promote the loss of redox homeostasis, ROS accumulation, and accelerate aging in yeast