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ImportanceStudies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.ObjectiveTo evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in children after heart transplant.Design, Setting, and ParticipantsMulticenter, randomized, open-label, clinical trial enrolling 211 patients who were alive 6 months after pediatric heart transplant at 25 US sites from February 2018 to August 2020. The last date of follow-up was April 17, 2023.InterventionsParticipants were randomized to receive everolimus and low-dose tacrolimus (n = 107) or standard-dose tacrolimus and mycophenolate mofetil (n = 104) for 30 months.Main Outcomes and MeasuresThe primary efficacy end point was the MATE-3 score at 30 months, a validated composite ordinal end point including acute cellular rejection, CAV, and CKD. The primary safety end point was the MATE-6 score, encompassing the MATE-3 score plus antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder.ResultsAmong 211 children randomized, the mean age was 8.2 (SD, 6.3) years, 97 (46%) underwent transplant for congenital heart disease, and 49 (23%) were treated for rejection before 6 months. At 30 months, the mean MATE-3 score did not differ between the 2 treatment groups (mean difference, −0.32; 95% CI, −0.90 to 0.20; P = .16). The mean MATE-6 score was no higher in the everolimus group than in the mycophenolate group (baseline-adjusted mean difference, −0.40; 95% CI, −1.81 to 0.93), meeting the success criterion for safety (noninferiority margin <3). There were no differences in graft survival, MATE-free survival, or freedom from any individual MATE. Everolimus was associated with greater improvement in estimated glomerular filtration rate at 12 months (mean difference, 10.5 mL/min/1.73 m2; 95% CI, 1.09-19.91 mL/min/1.73 m2) and a lower incidence of CMV infection (hazard ratio, 0.50; 95% CI, 0.26-0.93).Conclusions and RelevanceAmong 6-month pediatric heart transplant survivors, everolimus and low-dose tacrolimus did not differ from tacrolimus and mycophenolate in preventing the composite of cellular rejection, CAV, and CKD at 30 months. However, everolimus and low-dose tacrolimus appear to be safe based on the total burden of 6 MATEs and may be associated with improved kidney function and less CMV infection.Trial RegistrationClinicalTrials.gov Identifier: NCT03386539

Importance Cardiovascular (CV) disease is the leading cause of death globally for both men and women, yet women remain historically underrepresented in CV clinical trials, despite facing a disproportionately high burden of morbidity and mortality in many forms of CV disease. Objective To determine the representation of women across a broad range of CV trials. Evidence Review The participation of women in CV trials registered on ClinicalTrials.gov from 2017 to 2023 was systematically determined through the extraction of publicly available information. Data were extracted to identify the country of study, disease type, trial size, clinical intervention, and age of the participants. The proportion of women and the ratio of number of female to male participants (F:M ratio) were calculated for each trial. The women’s participation:prevalence ratio (PPR) was estimated for each trial based on the relative prevalence of the disease by sex in the specified region. Findings A total of 1079 registered CV trials were identified, including 1 396 104 participants, of whom 571 641 (41.0%) were women. The F:M ratio was significantly lower for studies on arrhythmia (median [IQR], 0.5), coronary heart disease (median [IQR], 0.39 [0.33-0.70]), acute coronary syndrome (median [IQR], 0.32 [0.24-0.51]), and heart failure (median [IQR], 0.51 [0.32-0.87]) but higher for obesity (median [IQR], 1.44 [1.08-4.50]) and pulmonary hypertension (median [IQR], 2.86 [1.50-3.97]) trials. The F:M ratio was higher for trials on lifestyle interventions (median [IQR], 1.51 [0.77-3.24]) than for drug trials. PPRs were low for clinical trials on coronary heart disease (median [IQR], 0.66 [0.50-0.86]), acute coronary syndrome (median [IQR], 0.79 [0.51-0.87]), and stroke (median [IQR], 0.74 [0.61-0.95]). Representation of women in CV trials varied by disease state, region, intervention, and sponsor type. Conclusions and Relevance These findings highlight both progress and persistent challenges in representation of women within CV trials. These gaps not only limit the generalizability of trial outcomes but also perpetuate inequities in evidence-based care for women with CV conditions.

BACKGROUND/OBJECTIVE Patient- and family-centered rounds (PFCR) have become a pediatric standard of care. However, rounds experiences of families using languages other than English (LOE)—particularly languages other than English or Spanish (LOES; eg, Arabic)—receive less focus. We aimed to identify differences in PFCR communication and engagement by language. METHODS We analyzed postintervention data from a 21-center structured PFCR study, assessing communication practices, quality, and family and nurse engagement during PFCR. Logistic regression adjusted by site compared PFCR between families using (1) LOE vs English, (2) Spanish vs English, and (3) LOES vs English. RESULTS Among 3051 PFCR encounters, 348 (11.4%) involved LOE (Spanish = 260; LOES = 85). Interpretation was not used in 7.2%, 5.8%, and 9.4% of encounters using LOE, Spanish, and LOES, respectively. PFCR in the following groups had lower adjusted odds (adjusted odds ratio [95% CI]) for the following domains: (1) LOE vs English: including providing verbal patient summaries (0.66 [0.46–0.95]), explaining diagnoses and differentials (0.62 [0.44–0.88]), family engagement (0.34 [0.20–0.57]), nursing inclusion (0.75 [0.60–0.93]), and nursing engagement (0.69 [0.52–0.90]). (2) Spanish vs English: diagnoses/differentials being explained (0.56 [0.37–0.85]), family engagement (0.35 [0.18–0.67]), nursing inclusion (0.77 [0.59–1.00]), and nursing engagement (0.68 [0.52–0.89]). (3) LOES vs English: families sharing concerns (0.66 [0.47–0.93]), family engagement (0.30 [0.16–0.54]), and nursing inclusion (0.74 [0.55–0.99]). CONCLUSION Even after implementing a PFCR intervention, families using LOE—especially LOES—experienced significant disparities in communication and engagement. Future approaches to improving PFCR should emphasize language access and promote nurse and family engagement for families using LOE, particularly LOES.

Abstract Background and Aims Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. Methods An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. Results A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80–30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06–5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27–3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (<30 years) disease (OR, 4.75; 95% CI, 2.35–9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08–.23). Conclusions Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.

Abstract Anti-IgLON5 disease is an autoimmune encephalitis that presents with a heterogenous clinical phenotype, including sleep disorders, movement abnormalities and bulbar involvement. It is characterized by autoantibodies against IgLON5, 85% association with HLA-DQB1*05:∼ and a brainstem-dominant tauopathy. Cellular and murine models report pathogenic effects of the autoantibodies, and neurodegenerative factors suggest progressive atrophy as a common sequela. However, evidence from in vivo patient data and long-term follow-up is limited, and the degree of progression remains elusive. In this multicentre study, clinical and brain MRI data were collected from 127 patients across 12 countries to investigate the relationships between clinical presentations and the development of distinct brain atrophy patterns. Our data show that most patients develop a complex multisystem phenotype as the disease progresses; however, neuromuscular manifestations rarely emerge at later disease stages. By comparison to healthy controls, this disease presents with severe substructure-specific atrophy, especially affecting the hypothalamus, brainstem, accumbens and basal ganglia, which, in age-independent analyses, show significant ventricular enlargement and also suggest progression of brainstem atrophy over the disease course. Moreover, the focality of atrophy was functionally linked to specific symptoms, with more severe involvement of the basal ganglia in patients with movement disorders, and greater atrophy in the hippocampus and thalamus in patients with cognitive impairment. Taken together, our results provide evidence of distinct atrophy patterns in anti-IgLON5 disease, which closely mirror sites of pathophysiologic processes, including autoantibody binding and tau deposition. Our data emphasize the brainstem as the pathophysiological hub of the disease and provide normative data for the incorporation of atrophy measurements into routine clinical assessments and future treatment studies to monitor disease trajectory and evaluate future treatment strategies.

Context.— After-death care can be complicated and time-consuming for clinical staff, and frustrating for bereaved families. Delays and errors can have damaging legal and reputational consequences for hospitals. Offices of Decedent Affairs (ODAs) have been proposed as a solution, and their potential benefits have been described in several single institution reports. The literature lacks a contemporary and comprehensive review of existing ODAs and their approaches. Objective.— To describe the process of establishing a new ODA and to provide a snapshot of the spectrum of structure, function, and impact of existing ODAs in the United States. Design.— A survey was administered to 11 established ODAs spread across the continental United States. Programs were identified through the College of American Pathologists Autopsy Committee and a Medical Autopsy Listserv. Results.— Eleven ODAs returned the survey, representing more than 190 cumulative years of experience in decedent care in the hospital setting (median, 10 years). There was a wide range in staffing (both staff size and background) as well as scope of services offered. The median ratio of hospital deaths to full-time equivalent (FTE) staffing was 360 deaths per FTE. Respondents reported that ODAs unburden clinical providers and facilitate decedent management. Some respondents reported a quicker turnover of hospital beds and shorter intervals between pronouncement of death and autopsy. ODAs increased autopsy rates when the autopsy services were part of the ODA. Conclusions.— This survey provides practical information for hospitals considering establishing a new ODA and useful benchmarks for existing ODA programs.

Context.— Decedent Affairs Offices and Programs can serve as an avenue to assist medical centers in facilitating efficient and comprehensive decedent management, despite a paucity of literature on their roles, establishment, and efficacy. Objective.— To characterize the motivations and rationales for establishing Decedent Affairs Offices. Design.— A survey was administered to 11 established Decedent Affairs Offices/Programs, identified through the College of American Pathologists Autopsy Committee and a Medical Autopsy Listserv. The questions comprehensively cover establishment, operations, and outcomes data available by institution. Results.— Survey respondents reported the rationale for starting their programs and the benefits such offices can have. Conclusions.— Decedent Affairs Offices and Programs provide a useful option to medical centers to navigate the increasingly complex task of comprehensive decedent management. The present survey helps to delineate the similarities and differences between these programs at 11 institutions, to aid nascent programs in their establishment and growth over time.

Abstract Introduction As the field of sexual medicine continues to grow, there has been increasing attention on methodological integrity and rigor of sexual medicine research, including an emphasis on guidelines for quantitative research design and standards for assessing clinical trial outcomes. However, qualitative research (QR) methodology has garnered relatively scant attention in comparison. Objectives To clarify the value of QR and provide recommendations for improving implementation of QR methods in sexual medicine research. Methods A PubMed review was conducted. Expert opinion was based on a process of literature review and expert consensus. Results An essential goal of QR is to describe and explain unknown or insufficiently understood phenomena through detailed investigation of subjective human experience. Results from QR allow for generating hypotheses that may then be tested. More recently, mixed-methods research, ie, research integrating both qualitative and quantitative methods, is being increasingly used across domains of biomedical and health science research. While there remain differences of opinion regarding use of qualitative methodology in sexual medicine, best-practice models of QR underscore the principle of trustworthiness and include ethics and transparency in protocols for data collection and analysis. It is recommended that established QR frameworks for developing a research question are utilized and that consolidated criteria for reporting research results are employed. Furthermore, authors and reviewers need training in both QR methods and qualitative reporting frameworks to be able to adequately report and review this type of research. Specific areas in sexual medicine that would ideally benefit from QR methods are suggested. Conclusion As the field of sexual medicine continues to expand, qualitative methodologies including mixed-methods research, offer significant value for understanding domains of inquiry that have not been thoroughly investigated. To achieve these targets, training of authors and reviewers on QR is needed.

PURPOSE Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy is used commonly for pediatric Hodgkin lymphoma (pHL) in low- and middle-income countries. The role of radiotherapy (RT) after ABVD in pHL is uncertain. MATERIALS AND METHODS We conducted a systematic review to explore the use of ABVD with or without RT in pHL. Key clinical questions included the number of cycles of ABVD, indications for and dose of RT, and outcomes by risk group. A search was performed in PubMed. Articles reporting survival outcomes by risk group were included. RESULTS Of 97 articles identified in the literature search, nine met inclusion criteria. Chemotherapy consisted of four to six cycles in limited disease and mostly six cycles in advanced disease. Three studies used RT for all patients within a specified risk group. Six studies dictated an adapted RT approach, with 3%-43% of the patients receiving RT for bulky adenopathy, slow early response (SER), and/or incomplete response. Radiation doses ranged between 20 and 36 Gy. The progression-free survival and overall survival at 4-10 years ranged from 84% to 100% and 93%-100% in limited disease and 50%-84.4% and 75%-95.3% in advanced disease, respectively. Studies did not directly assess the impact of certain chemotherapy or RT strategies. Recommendations were made after reviewing outcomes with particular approaches. CONCLUSION Four cycles of ABVD are recommended for limited disease, and six cycles of ABVD are recommended for advanced disease. In both limited and advanced diseases, RT is recommended with a dose of 20-21 Gy only to sites of bulky and/or SER, with a boost of up to 36 Gy to sites of incomplete response. This approach could spare radiation for at least half of the patients with limited disease and one third of advanced disease.