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Background: Acute rejection (AR) is a leading cause of early morbidity and mortality in heart transplant (HTx) recipients. There is limited data on donation after circulatory death (DCD) HTx recipients where ischemia reperfusion injury may contribute to the development of AR and may be detected early with noninvasive biomarkers, such as donor-derived cell-free DNA (dd-cfDNA) and gene expression profile (GEP). The goal of this study is to compare dd-cfDNA, GEP, and rejection outcomes in DCD and donation after brain death (DBD) HTx recipients. Methods: This single-center, retrospective study included DCD and DBD HTx recipients from January 2020 to September 2022. Patients were excluded from the study if dd-cfDNA and GEP were not available. The CareDx HeartCare platform was used to obtain dd-cfDNA (AlloSure-Heart) and GEP (AlloMap) with the highest values for each patient recorded at 6 and 12 months. The mean values for these noninvasive markers were compared between DCD and DBD groups. Patients were followed for clinical outcomes, including treated AR, cardiac allograft vasculopathy (CAV), and death, through September 2023. Results: A total of 156 HTx patients were included with 50 DCD and 106 DBD recipients. Baseline characteristics were similar between DCD and DBD recipients including mean age (58.5 vs 56.9 years, p = 0.48), male sex (82% vs 76%, p = 0.56), and Caucasian race (46% vs 43%, p = 0.78). There were no significant differences in mean AlloSure-Heart at 6 and 12 months between DCD and DBD recipients. AlloMap was significantly lower at 6 months (p = 0.04), but not at 12 months between DCD and DBD recipients. With respect to clinical outcomes at 1 year, there were no significant differences in treated AR (22% vs 14%, p = 0.32), International society of heart and lung transplant grade ≥2 CAV (0% vs 4%, p = 0.44), or mortality (2% vs 0%, p = 0.69) between DCD and DBD recipients. Conclusions: In this single-center study, there were no significant differences in mean dd-cfDNA and treated AR at 1 year between DCD and DBD HTx recipients. There was a significant increase in mean GEP at 6 months, but not at 12 months in the DBD cohort. Overall, there does not appear to be clinically significant cardiac allograft injury related to DCD as measured by noninvasive markers. Further work is needed to confirm these findings.

Abstract Background The COVID‐19 pandemic brought rapid and major changes to research, and those wishing to carry out Patient and Public Involvement (PPI) activities faced challenges, such as restrictions on movement and contact, illness, bereavement and risks to potential participants. Some researchers moved PPI to online settings during this time but remote consultations raise, as well as address, a number of challenges. It is important to learn from PPI undertaken in this period as face‐to‐face consultation may no longer be the dominant method for PPI. Methods UK stay‐at‐home measures announced in March 2020 necessitated immediate revisions to the intended face‐to‐face methods of PPI consultation for the ESORT Study, which evaluated emergency surgery for patients with common acute conditions. PPI plans and methods were modified to all components being online. We describe and reflect on: initial plans and adaptation; recruitment; training and preparation; implementation, contextualisation and interpretation. Through first‐hand accounts we show how the PPI processes were developed, experienced and viewed by different partners in the process. Discussion and Conclusions While concerns have been expressed about the possible limiting effects of forgoing face‐to‐face contact with PPI partners, we found important benefits from the altered dynamic of the online PPI environment. There were increased opportunities for participation which might encourage the involvement of a broader demographic, and unexpected benefits in that the online platform seemed to have a ‘democratising’ effect on the meetings, to the benefit of the PPI processes and outcomes. Other studies may however find that their particular research context raises particular challenges for the use of online methods, especially in relation to representation and inclusion, as new barriers to participation may be raised. It is important that methodological challenges are addressed, and researchers provide detailed examples of novel methods for discussion and empirical study. Patient and Public Contribution We report a process which involved people with lived experience of emergency conditions and members of the public. A patient member was involved in the design and implementation, and two patients with lived experience contributed to the manuscript.

Background: Evidence is required on the clinical effectiveness and cost-effectiveness of emergency surgery compared with non-emergency surgery strategies (including medical management, non-surgical procedures and elective surgery) for patients admitted to hospital with common acute gastrointestinal conditions. Objectives: We aimed to evaluate the relative (1) clinical effectiveness of two strategies (i.e. emergency surgery vs. non-emergency surgery strategies) for five common acute conditions presenting as emergency admissions; (2) cost-effectiveness for five common acute conditions presenting as emergency admissions; and (3) clinical effectiveness and cost-effectiveness of the alternative strategies for specific patient subgroups. Methods: The records of adults admitted as emergencies with acute appendicitis, cholelithiasis, diverticular disease, abdominal wall hernia or intestinal obstruction to 175 acute hospitals in England between 1 April 2010 and 31 December 2019 were extracted from Hospital Episode Statistics and linked to mortality data from the Office for National Statistics. Eligibility was determined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis codes, which were agreed by clinical panel consensus. Patients having emergency surgery were identified from Office of Population Censuses and Surveys procedure codes. The study addressed the potential for unmeasured confounding with an instrumental variable design. The instrumental variable was each hospital’s propensity to use emergency surgery compared with non-emergency surgery strategies. The primary outcome was the ‘number of days alive and out of hospital’ at 90 days. We reported the relative effectiveness of the alternative strategies overall, and for prespecified subgroups (i.e. age, number of comorbidities and frailty level). The cost-effectiveness analyses used resource use and mortality from the linked data to derive estimates of incremental costs, quality-adjusted life-years and incremental net monetary benefits at 1 year. Results: Cohort sizes were as follows: 268,144 admissions with appendicitis, 240,977 admissions with cholelithiasis, 138,869 admissions with diverticular disease, 106,432 admissions with a hernia and 133,073 admissions with an intestinal obstruction. Overall, at 1 year, the average number of days alive and out of hospitals at 90 days, costs and quality-adjusted life-years were similar following either strategy, after adjusting for confounding. For each of the five conditions, overall, the 95% confidence intervals (CIs) around the incremental net monetary benefit estimates all included zero. For patients with severe frailty, emergency surgery led to a reduced number of days alive and out of hospital and was not cost-effective compared with non-emergency surgery, with incremental net monetary benefit estimates of –£18,727 (95% CI –£23,900 to –£13,600) for appendicitis, –£7700 (95% CI –£13,000 to –£2370) for cholelithiasis, –£9230 (95% CI –£24,300 to £5860) for diverticular disease, –£16,600 (95% CI –£21,100 to –£12,000) for hernias and –£19,300 (95% CI –£25,600 to –£13,000) for intestinal obstructions. For patients who were ‘fit’, emergency surgery was relatively cost-effective, with estimated incremental net monetary benefit estimates of £5180 (95% CI £684 to £9680) for diverticular disease, £2040 (95% CI £996 to £3090) for hernias, £7850 (95% CI £5020 to £10,700) for intestinal obstructions, £369 (95% CI –£728 to £1460) for appendicitis and £718 (95% CI £294 to £1140) for cholelithiasis. Public and patient involvement translation workshop participants emphasised that these findings should be made widely available to inform future decisions about surgery. Limitations: The instrumental variable approach did not eliminate the risk of confounding, and the acute hospital perspective excluded costs to other providers. Conclusions: Neither strategy was more cost-effective overall. For patients with severe frailty, non-emergency surgery strategies were relatively cost-effective. For patients who were fit, emergency surgery was more cost-effective. Future work: For patients with multiple long-term conditions, further research is required to assess the benefits and costs of emergency surgery. Study registration: This study is registered as reviewregistry784. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 11, No. 1. See the NIHR Journals Library website for further project information.

Abstract Background The persistence of racial/ethnic inequities in rates of engagement along the HIV care continuum signals the need for novel approaches. We developed six behavioral intervention components for use in an optimization trial, grounded in a model that integrates critical race theory, harm reduction, and self-determination theory, designed to address various barriers that African American/Black and Latino persons living with HIV (PLWH) experience to the HIV care continuum. The components were: health education, motivational interviewing sessions, pre-adherence skill building, peer mentorship, focused support groups, and navigation. The present qualitative exploratory study describes participants’ perspectives on the components’ acceptability, feasibility, and impact. Methods Participants were African American/Black and Latino PLWH poorly engaged in HIV care and with non-suppressed HIV viral load in New York City. From a larger trial, we randomly selected 46 participants for in-depth semi-structured interviews. Interviews were audio-recorded and transcribed verbatim, and data were analyzed using directed content analysis. Quantitative data on sociodemographic and background characteristics and components’ acceptability and feasibility were also collected. Results On average, participants were 49 years old and had lived with HIV for 19 years. Most were cisgender-male and African American/Black. Participants reported a constellation of serious social and structural challenges to HIV management including chronic poverty, unstable housing, and stigma. Across components, a non-judgmental and pressure-free approach and attention to structural and cultural factors were seen as vital to high levels of engagement, but lacking in most medical/social service settings. Prominent aspects of individual components included establishing trust (health education); developing intrinsic motivation, goals, and self-reflection (motivational interviewing sessions); learning/practicing adherence strategies and habits (pre-adherence skill building); reducing social isolation via peer role models (peer mentorship); reflecting on salient goals and common challenges with peers without stigma (focused support groups); and circumventing structural barriers to HIV management with support (navigation). Components were found acceptable and feasible. Findings suggested ways components could be improved. Conclusions The present study advances research on interventions for African American/Black and Latino PLWH, who experience complex barriers to engagement along the HIV care continuum. Future study of the components is warranted to address racial/ethnic health inequities in HIV.

Abstract Background Rates of participation in HIV care, medication uptake, and viral suppression are improving among persons living with HIV (PLWH) in the United States. Yet, disparities among African American/Black and Latino PLWH are persistent, signaling the need for new conceptual approaches. To address gaps in services and research (e.g., insufficient attention to structural/systemic factors, inadequate harm reduction services and autonomy support) and improve behavioral interventions, we integrated critical race theory, harm reduction, and self-determination theory into a new conceptual model, then used the model to develop a set of six intervention components which were tested in a larger study. The present qualitative study explores participants’ perspectives on the study’s acceptability, feasibility, and impact, and the conceptual model’s contribution to these experiences. Methods Participants in the larger study were African American/Black and Latino PLWH poorly engaged in HIV care and with non-suppressed HIV viral load in New York City (N = 512). We randomly selected N = 46 for in-depth semi-structured interviews on their experiences with and perspectives on the study. Interviews were audio-recorded and professionally transcribed verbatim, and data were analyzed using directed qualitative content analysis. Results On average, participants were 49 years old (SD = 9) and had lived with HIV for 19 years (SD = 7). Most were male (78%) and African American/Black (76%). All had taken HIV medication previously. Challenging life contexts were the norm, including poverty, poor quality/unstable housing, trauma histories exacerbated by current trauma, health comorbidities, and substance use. Participants found the study highly acceptable. We organized results into four themes focused on participants’ experiences of: 1) being understood as a whole person and in their structural/systemic context; 2) trustworthiness and trust; 3) opportunities for self-reflection; and 4) support of personal autonomy. The salience of nonjudgment was prominent in each theme. Themes reflected grounding in the conceptual model. Participants reported these characteristics were lacking in HIV care settings. Conclusions The new conceptual model emphasizes the salience of systemic/structural and social factors that drive health behavior and the resultant interventions foster trust, self-reflection, engagement, and behavior change. The model has potential to enhance intervention acceptability, feasibility, and effectiveness with African American/Black and Latino PLWH.

Abstract Background Among those at highest risk for COVID-19 exposure is the large population of frontline essential workers in occupations such food service, retail, personal care, and in-home health services, among whom Black and Latino/Hispanic persons are over-represented. For those not vaccinated and at risk for exposure to COVID-19, including frontline essential workers, regular (approximately weekly) COVID-19 testing is recommended. However, Black and Latino/Hispanic frontline essential workers in these occupations experience serious impediments to COVID-19 testing at individual/attitudinal- (e.g., lack of knowledge of guidelines), social- (e.g., social norms), and structural-levels of influence (e.g., poor access), and rates of testing for COVID-19 are insufficient. Methods/design The proposed community-engaged study uses the multiphase optimization strategy (MOST) framework and an efficient factorial design to test four candidate behavioral intervention components informed by an integrated conceptual model that combines critical race theory, harm reduction, and self-determination theory. They are A) motivational interview counseling, B) text messaging grounded in behavioral economics, C) peer education, and D) access to testing (via navigation to an appointment vs. a self-test kit). All participants receive health education on COVID-19. The specific aims are to: identify which components contribute meaningfully to improvement in the primary outcome, COVID-19 testing confirmed with documentary evidence, with the most effective combination of components comprising an “optimized” intervention that strategically balances effectiveness against affordability, scalability, and efficiency (Aim 1); identify mediators and moderators of the effects of components (Aim 2); and use a mixed-methods approach to explore relationships among COVID-19 testing and vaccination (Aim 3). Participants will be N = 448 Black and Latino/Hispanic frontline essential workers not tested for COVID-19 in the past six months and not fully vaccinated for COVID-19, randomly assigned to one of 16 intervention conditions, and assessed at 6- and 12-weeks post-baseline. Last, N = 50 participants will engage in qualitative in-depth interviews. Discussion This optimization trial is designed to yield an effective, affordable, and efficient behavioral intervention that can be rapidly scaled in community settings. Further, it will advance the literature on intervention approaches for social inequities such as those evident in the COVID-19 pandemic. Trial registration ClinicalTrials.gov: NCT05139927 ; Registered on 11/29/2021. Protocol version 1.0. May 2, 2022, Version 1.0