Visualizing subcellular changes in the NAD(H) pool size versus redox state using fluorescence lifetime imaging microscopy of NADH.

NADH autofluorescence imaging is a promising approach for visualizing energy metabolism at the single-cell level. However, it is sensitive to the redox ratio and the total NAD(H) amount, which can change independently from each other, for example with aging. Here, we evaluate the potential of fluorescence lifetime imaging microscopy (FLIM) of NADH to differentiate between these modalities.We perform targeted modifications of the NAD(H) pool size and ratio in cells and mice and assess the impact on NADH FLIM. We show that NADH FLIM is sensitive to NAD(H) pool size, mimicking the effect of redox alterations. However, individual components of the fluorescence lifetime are differently impacted by redox versus pool size changes, allowing us to distinguish both modalities using only FLIM. Our results emphasize NADH FLIM's potential for evaluating cellular metabolism and relative NAD(H) levels with high spatial resolution, providing a crucial tool for our understanding of aging and metabolism.

Serious illness communication skills training for emergency physicians and advanced practice providers: a multi-method assessment of the reach and effectiveness of the intervention.

BACKGROUND: EM Talk is a communication skills training program designed to improve emergency providers' serious illness conversational skills. Using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, this study aims to assess the reach of EM Talk and its effectiveness. METHODS: EM Talk consisted of one 4-h training session during which professional actors used role-plays and active learning to train providers to deliver serious/bad news, express empathy, explore patients' goals, and formulate care plans. After the training, emergency providers filled out an optional post-intervention survey, which included course reflections. Using a multi-method analytical approach, we analyzed the reach of the intervention quantitatively and the effectiveness of the intervention qualitatively using conceptual content analysis of open-ended responses. RESULTS: A total of 879 out of 1,029 (85%) EM providers across 33 emergency departments completed the EM Talk training, with the training rate ranging from 63 to 100%. From the 326 reflections, we identified meaning units across the thematic domains of improved knowledge, attitude, and practice. The main subthemes across the three domains were the acquisition of Serious Illness (SI) communication skills, improved attitude toward engaging qualifying patients in SI conversations, and commitment to using these learned skills in clinical practice. CONCLUSION: Our study showed the extensive reach and the effectiveness of the EM Talk training in improving SI conversation. EM Talk, therefore, can potentially improve emergency providers' knowledge, attitude, and practice of SI communication skills. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03424109; Registered on January 30, 2018.

Advancing patient-centered research practices in a pragmatic patient-level randomized clinical trial: A thematic analysis of stakeholder engagement in Emergency Medicine Palliative Care Access (EMPallA).

BACKGROUND: Involving patient and community stakeholders in clinical trials adds value by ensuring research prioritizes patient goals both in conduct of the study and application of the research. The use of stakeholder committees and their impact on the conduct of a multicenter clinical trial have been underreported clinically and academically. The aim of this study is to describe how Study Advisory Committee (SAC) recommendations were implemented throughout the Emergency Medicine Palliative Care Access (EMPallA) trial. EMPallA is a multi-center, pragmatic two-arm randomized controlled trial (RCT) comparing the effectiveness of nurse-led telephonic case management and specialty, outpatient palliative care of older adults with advanced illness. METHODS: A SAC consisting of 18 individuals, including patients with palliative care experience, members of healthcare organizations, and payers was convened for the EMPallA trial. The SAC engaged in community-based participatory research and assisted in all aspects from study design to dissemination. The SAC met with the research team quarterly and annually from project inception to dissemination. Using meeting notes and recordings we completed a qualitative thematic analysis using an iterative process to develop themes and subthemes to summarize SAC recommendations throughout the project's duration. RESULTS: The SAC convened 16 times between 2017 and 2020. Over the course of the project, the SAC provided 41 unique recommendations. Twenty-six of the 41 (63%) recommendations were adapted into formal Institutional Review Board (IRB) study modifications. Recommendations were coded into four major themes: Scientific, Pragmatic, Resource and Dissemination. A majority of the recommendations were related to either the Scientific (46%) or Pragmatic (29%) themes. Recommendations were not mutually exclusive across three study phases: Preparatory, execution and translational. A vast majority (94%) of the recommendations made were related to the execution phase. Major IRB study modifications were made based on their recommendations including data collection of novel dependent variables and expanding recruitment to Spanish-speaking patients. CONCLUSIONS: Our study provides an example of successful integration of a SAC in the conduct of a pragmatic, multi-center RCT. Future trials should engage with SACs in all study phases to ensure trials are relevant, inclusive, patient-focused, and attentive to gaps between health care and patient and family needs. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03325985, 10/30/2017.

Clinical research should involve patient and community stakeholder perspectives to make sure the study addresses questions important to the studied population. One way to do this is by creating a group of stakeholders who can advise on the conduct of a study. We assembled a Study Advisory Committee (SAC) for the Emergency Medicine Palliative Care Access (EMPallA) trial. The purpose of this clinical trial is to compare the effectiveness of nurse-led telephonic case management and specialty, outpatient palliative care of older adults with advanced illness. This paper describes how the SACs involvement translated into direct impacts on the EMPallA trial. The trial research team held regular meetings with the SAC throughout the trial process. Their involvement led to many significant changes in the trial, such as  expanding recruitment inclusion criteria (Spanish-speaking patients), and including survey instruments to measure lonelines and caregiver burden. The SAC also devised strategies to overcome patient and caregiver recruitment and retention challenges, including the creation of patient-friendly materials and training for research coordinators. This study provides a successful example of how actively engaging patient and community stakeholders, through committee engagement, can promote patient priorities in all phases of a trial while facilitating patient recruitment and retention.

Emergency Nurses' Perceived Barriers and Solutions to Engaging Patients With Life-Limiting Illnesses in Serious Illness Conversations: A United States Multicenter Mixed-Method Analysis.

INTRODUCTION: This study aimed to assess emergency nurses' perceived barriers toward engaging patients in serious illness conversations. METHODS: Using a mixed-method (quant + QUAL) convergent design, we pooled data on the emergency nurses who underwent the End-of-Life Nursing Education Consortium training across 33 emergency departments. Data were extracted from the End-of-Life Nursing Education Consortium post-training questionnaire, comprising a 5-item survey and 1 open-ended question. Our quantitative analysis employed a cross-sectional design to assess the proportion of emergency nurses who report that they will encounter barriers in engaging seriously ill patients in serious illness conversations in the emergency department. Our qualitative analysis used conceptual content analysis to generate themes and meaning units of the perceived barriers and possible solutions toward having serious illness conversations in the emergency department. RESULTS: A total of 2176 emergency nurses responded to the survey. Results from the quantitative analysis showed that 1473 (67.7%) emergency nurses reported that they will encounter barriers while engaging in serious illness conversations. Three thematic barriers-human factors, time constraints, and challenges in the emergency department work environment-emerged from the content analysis. Some of the subthemes included the perceived difficulty of serious illness conversations, delay in daily throughput, and lack of privacy in the emergency department. The potential solutions extracted included the need for continued training, the provision of dedicated emergency nurses to handle serious illness conversations, and the creation of dedicated spaces for serious illness conversations. DISCUSSION: Emergency nurses may encounter barriers while engaging in serious illness conversations. Institutional-level policies may be required in creating a palliative care-friendly emergency department work environment.

Serious Illness Communication Skills Training for Emergency Physicians and Advanced Practice Providers: A Multi-Method Assessment of the Reach and Effectiveness of the Intervention.

Background: EM Talk is a communication skills training program designed to improve emergency providers' serious illness conversational skills. Using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, this study aims to assess the reach of EM Talk and its effectiveness. Methods: EM Talk is one of the components of Primary Palliative Care for Emergency Medicine (EM) intervention. It consisted of one 4-hour training session during which professional actors used role-plays and active learning to train providers to deliver serious/bad news, express empathy, explore patients' goals, and formulate care plans. After the training, emergency providers filled out an optional post-intervention survey, which included course reflections. Using a multi-method analytical approach, we analyzed the reach of the intervention quantitatively and the effectiveness of the intervention qualitatively using conceptual content analysis of open-ended responses. Results: A total of 879 out of 1,029 (85%) EM providers across 33 emergency departments completed the EM Talk training, with the training rate ranging from 63-100%. From the 326 reflections, we identified meaning units across the thematic domains of improved knowledge, attitude, and practice. The main subthemes across the three domains were the acquisition of discussion tips and tricks, improved attitude toward engaging qualifying patients in serious illness (SI) conversations, and commitment to using these learned skills in clinical practice. Conclusion: Effectively engaging qualifying patients in serious illness conversations requires appropriate communication skills. EM Talk has the potential to improve emergency providers' knowledge, attitude, and practice of SI communication skills. Trial registration: NCT03424109.