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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.

Background: The events of 9/11 and the October 2002 National Intelligence Estimate on Iraq’s Continuing Programs for Weapons of Mass Destruction precipitated fundamental changes within the United States Intelligence Community. As part of the reform, analytic tradecraft standards were revised and codified into a policy document – Intelligence Community Directive (ICD) 203 – and an analytic ombudsman was appointed in the newly created Office for the Director of National Intelligence to ensure compliance across the intelligence community. In this paper we investigate the untested assumption that the ICD203 criteria can facilitate reliable evaluations of analytic products.Methods: Fifteen independent raters used a rubric based on the ICD203 criteria to assess the quality of reasoning of 64 analytical reports generated in response to hypothetical intelligence problems. We calculated the intra-class correlation coefficients for single and group-aggregated assessments.Results: Despite general training and rater calibration, the reliability of individual assessments was poor. However, aggregate ratings showed good to excellent reliability.Conclusion: Given that real problems will be more difficult and complex than our hypothetical case studies, we advise that groups of at least three raters are required to obtain reliable quality control procedures for intelligence products. Our study sets limits on assessment reliability and provides a basis for further evaluation of the predictive validity of intelligence reports generated in compliance with the tradecraft standards.

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

Abstract Background Persons living with HIV (PLWH) are living longer, although racial/ethnic and socioeconomic status (SES) disparities persist. Yet, little is known about the experience of living with and managing HIV over decades. The present study took a qualitative approach and used the lens of symbolic violence, a type of internalized, non-physical violence manifested in the power differential between social groups. We focused on adult African American/Black and Latinx (AABL) PLWH from low-SES backgrounds. Methods Data were drawn from two studies with AABL PLWH in New York City (N = 59). After providing signed informed consent, participants engaged in in-depth semi-structured interviews on aspects of HIV management. Interviews were audio-recorded and professionally transcribed verbatim, and data were analyzed using directed qualitative content analysis. Results Participants in the two studies were comparable on sociodemographic and background characteristics. They had lived with HIV for 20 years, on average (range 3–33 years). All were from low-SES backgrounds and most were African American/Black and men. Participants experienced a convergence of multiple social exclusions, harms, and stigmas, consistent with symbolic violence, which contributed to disengagement from HIV care and discontinuation of HIV medications. We organized results into five sub-themes: (1) participants were “ground down” over time by material, social, and emotional challenges and this diminished self-worth and, at times, the will to live; (2) social isolation and self-isolation, based in part on feeling devalued and dehumanized, served as stigma-avoidance strategies and mechanisms of social exclusion; (3) stigmatizing aspects of patient-provider interactions, both experienced and anticipated, along with (4) restricted autonomy in HIV care and other settings (e.g., parole) reduced engagement; and (5) poor HIV management was internalized as a personal failure. Importantly, resilience was evident throughout the five sub-themes. Conclusions Symbolic violence is a useful framework for understanding long-term HIV management and survivorship among AABL PLWH from low-SES backgrounds. Indeed, forms of symbolic violence are internalized over time (e.g., experiencing devaluation, dehumanization, loss of self-worth, and anticipated stigma), thereby impeding successful HIV management, in part because avoiding HIV care and discontinuing HIV medications are primary coping strategies. Results have implications for interventions in community and health care settings.

Abstract Birt–Hogg–Dubé (BHD) syndrome is a rare, autosomal dominant disorder caused by a germline mutation in the folliculin gene (17p11.2). It is characterized by benign skin lesions, renal tumours, and pulmonary cysts, with pneumothoraces seen exceptionally rarely in patients younger than 40 years. We report the case of a 15‐year‐old boy who presented with sudden onset left‐sided chest pain and acute dyspnoea secondary to a large left‐sided pneumothorax. This failed to resolve despite chest drain insertion and he required video‐assisted thoracoscopic surgical pleurodesis, which revealed macroscopic pulmonary cyst formation. Following this, he made a good recovery and a further high‐resolution computerized tomography (CT) scan of his chest identified multiple, small, subpleural parenchymal lung cysts that were not initially visible on prior imaging. Further questioning revealed a strong family history of spontaneous pneumothoraces and additional genomic sequencing confirmed a diagnosis of BHD syndrome. We highlight the diagnostic, management, and surveillance challenges for this rare syndrome.

Runaway and homeless youth (RHY) comprise a large population of young people who reside outside the control and protection of parents and guardians and who experience numerous traumas and risk factors, but few buffering resources. Specialized settings have developed to serve RHY, but little is known about their effects. The present cross-sectional qualitative descriptive study, grounded in the positive youth development approach and the Youth Program Quality Assessment model, addressed this gap in the literature. From a larger sample of 29 RHY-specific settings across New York State, RHY ages 16–21 from 11 settings were purposively sampled for semi-structured in-depth interviews on their transitions into homelessness, experiences with settings, and unmet needs (N = 37 RHY). Data were analyzed with a theory-driven and inductive systematic content analysis approach. Half of participants (54%) were female; almost half (49%) identified as non-heterosexual; and 42% were African American/Black, 31% were Latino/Hispanic, and 28% were White/other. Results indicated that because RHY are a uniquely challenged population, distrustful of service settings and professional adults and skilled at surviving independently, the population-tailored approaches found in RHY-specific settings are vital to settings’ abilities to effectively engage and serve RHY. We found the following four major themes regarding the positive effects of settings: (1) engaging with an RHY setting was emotionally challenging and frightening, and thus the experiences of safety and services tailored to RHY needs were critical; (2) instrumental support from staff was vital and most effective when received in a context of emotional support; (3) RHY were skilled at survival on the streets, but benefited from socialization into more traditional systems to foster future independent living; and (4) follow-through and aftercare were needed as RHY transitioned out of services. With respect to gaps in settings, RHY highlighted the following: (1) a desire for better management of tension between youths’ needs for structure and wishes for autonomy and (2) lack of RHY input into program governance. This study advances our understanding of RHY, their service needs, and the ways settings meet these needs, as well as remaining gaps. It underscores the vital, life-changing, and even life-saving role these settings play for RHY.