Citations

Background: Fecal microbiota, live-jslm (RBL) is a microbiota-based product for the prevention of recurrent Clostridioides difficile infection (rCDI) in adults following antibiotic treatment. The safety and clinical effectiveness of RBL administered via colonoscopy in adults with rCDI were evaluated in CDI-SCOPE. An 8-week analysis showed 9.8% of participants had RBL-related treatment-emergent adverse events (TEAEs; primary endpoint) and 95.1% experienced treatment success (no CDI recurrence). Objectives: To evaluate long-term safety and clinical effectiveness of RBL through 6 months of follow-up in CDI-SCOPE. Design: Single-arm exploratory phase IIIb trial conducted at 12 sites in the United States. Methods: Eligible adults with rCDI received a single 150-mL dose of RBL to the right colon via colonoscopy. The primary endpoint was RBL-related TEAEs through 8 weeks after RBL administration or confirmed treatment failure. Secondary endpoints included safety up to 6 months after RBL administration. Exploratory analyses included assessment of further CDI episodes. Results: Of the 41 participants enrolled, 39 completed trial assessments through 6 months. From 8 weeks through 6 months after RBL administration, 36 TEAEs in 15 participants (36.6%) were reported, one of which (irritable bowel syndrome) was RBL-related; most TEAEs (97.2%) were of mild or moderate severity. Over the 6-month trial period, 23 participants (56.1%) experienced 69 TEAEs; 94.2% were of mild or moderate severity. Serious TEAEs occurred in three participants (7.3%), none of which were related to RBL or its administration, and no TEAEs led to discontinuation or death. Overall, 38 participants (92.7%) did not experience further CDI episodes, 1 (2.4%) did between 8 weeks and 6 months, and 2 (4.9%) had an indeterminate outcome due to trial withdrawal before 8 weeks. Conclusion: RBL administered via colonoscopy was safe and effective for preventing CDI recurrence in adults with rCDI in CDI-SCOPE. Trial registration: ClinicalTrials.gov: NCT05831189.

Abstract Background and Objectives To assess the efficacy of a local volunteer program, delirium optimization with volunteer engagement (DOVE), in preventing in-hospital delirium. Research Design and Methods Between February 2023 and June 2024, volunteers provided structured interventions to patients at risk for delirium, as identified by the Delirium Risk Assessment (DRA) score. Interventions are humanities-based and included sensory aide assistance, completion of “get to know me” forms, and conversation. Data were retrospectively acquired from electronic health records and compared to a control cohort from another medical unit. Delirium occurrence was captured when the nursing confusion assessment method (CAM) documentation was positive, or a clinician documented delirium diagnoses. Cohorts were matched 1:2 (DOVE vs Control) by age, gender, DRA score, month/year of admission, and length of hospital stay. Results A total of 168 patients received interventions by DOVE volunteers, of which 139 were matched with 261 controls. In-hospital delirium occurrence was lower in the DOVE cohort compared to the control cohort (46.8% vs 56.7%; p = .015). Conditional logistic regressions demonstrated a lower odds ratio (OR) for delirium occurrence, 0.55 (95% confidence interval [CI]; 0.34–0.89; p = .015) associated with DOVE intervention. Subgroup analyses of delirium occurrence among patients with DRA score of 3–4 demonstrated an OR of 0.56 (95% CI; 0.31–1.01; p = .053) between the DOVE and control cohorts. Discussion and Implications In-hospital delirium occurrence was ∼10% lower among DOVE cohort patients. This humanities-based intervention offers a feasible strategy, particularly during times of staffing shortages, and should be considered for broader implementation across healthcare institutions.

ABSTRACT INTRODUCTION Neighborhood deprivation increases dementia risk, although mechanisms remain unclear. We tested a framework in which modifiable risk factors and cerebral small vessel disease (SVD) mediate the link between neighborhood deprivation and cognition. METHODS In 585 cognitively healthy midlife adults (ages 40–59), neighborhood deprivation was derived from postcodes, cognition was assessed using the COGNITO, lifestyle risk factors were measured using clinical assessments, and SVD (white matter hyperintensities, lacunes, microbleeds, perivascular spaces) was assessed on 3T magnetic resonance imaging. Multivariate analyses examined association pathways among these variables. RESULTS Neighborhood deprivation was associated with poorer cognition ( r = 0.36, p < 0.001), greater prevalence of modifiable risk factors ( r = 0.36, p < 0.001), and greater SVD burden ( β = 0.18, p = 0.008). Serial mediation showed that the effects of deprivation on cognition were indirect, possibly operating via lifestyle risk and SVD, explaining 20% of the total effect, whereas SVD alone explained 28%. DISCUSSION Neighborhood disadvantage relates to poorer cognition, possibly mediated through vascular risk factors and cerebrovascular disease. Highlights Neighborhood deprivation linked to poorer cognition in healthy midlife adults Deprivation linked to small vessel disease (SVD) and modifiable risk factors (chiefly cardiovascular risk) Association between deprivation and cognition mediated by modifiable risk and SVD Mediation was exclusive to hypertensive SVD, but not cerebral amyloid angiopathy (CAA)‐related SVD

Acute exposure to hypoxia will induce right ventricular (RV) hemodynamic changes and may increase the degree of right-to-left shunting, which can contribute to dyspnea at altitude. In this retrospective study, 125 patients (median age 66 years; 50.4% women) with unexplained dyspnea at altitude underwent hypoxic simulation testing (HST) with transthoracic echocardiography (TTE). During simulated hypoxia (mode (Min-Max) altitude: 8000 (6000–18,000) ft, were observed a significant decrease in oxygen saturation (97% (95–98) vs. 88% (82–92), p < 0.001) and RV free wall longitudinal strain (−19.6 ± 3.99% vs. −17.3 ± 4.17%, p < 0.01), an increase in RV systolic pressure (RVSP: 26 (23–30.5) vs. 29 (25–36.5) mmHg, p < 0.001). No significant changes were observed in TAPSE (20 (18–23) vs. 20 (19–24) mm) or S wave (0.12 (0.11–0.14) vs. 0.13 (0.12–0.14) m/s). Right-to-left shunting was present in 47.2% of patients and 11.9% exhibited inducible shunting only under hypoxia. However, under hypoxia, there were no significant differences in RV hemodynamic parameters or saturation between those with and without shunting. TTE with HST is useful to characterize both cardiopulmonary response and the dynamic changes in right-to-left shunt behavior under hypoxic stress.

Background/Objectives: Erythromelalgia is a rare condition characterized by burning pain, redness, and warmth primarily in the extremities, usually worsened by heat and alleviated by cold. The objective of this study was to identify the top 10 priorities in pediatric erythromelalgia from multiple perspectives, including clinicians, people with lived experience of childhood-onset erythromelalgia, and their family members. Methods: A modified James Lind Alliance Priority-Setting Process was conducted. The top priorities were identified through four phases: (1) an international online survey to gather priorities, (2) data processing, (3) an interim prioritization online survey, and (4) a virtual workshop to set the final priorities. Results: In phase 1, 185 potential priorities were submitted by 74 respondents (53% patients, 24% family members, and 23% clinicians) that were developed into 68 unique research questions (phase 2). In phase 3, of the 68 questions, 50 were rated for importance by 58 participants (38% patients, 36% family members, and 26% clinicians), reducing the list to 25 questions. In phase 4, the top 10 was reached through consensus by 12 participants (33% patients, 25% family members, and 42% clinicians) across Canada, South Africa, the United States of America, and the United Kingdom. Conclusions: The final priorities focused on the treatment of erythromelalgia, understanding underlying mechanisms, the association of erythromelalgia with various body systems, and generating awareness. This list is the first international patient-centered research agenda for childhood-onset erythromelalgia and a call to action from key partners to improve future research and care.

Background: Spontaneous Coronary Artery Dissection (SCAD) is a cause of acute coronary syndrome, particularly among women, and is associated with psychological distress, including depression, anxiety, and post-traumatic stress (PTSD) symptoms. Fibromuscular dysplasia (FMD), a vascular condition that alters the arteries, is often found in patients with SCAD, adding complexity and uncertainty with a second serious diagnosis. This study examined the differences in mental health symptoms between SCAD survivors with and without FMD to better understand their unique psychosocial needs and inform interventions to enhance patient outcomes. Methods: Patients diagnosed with SCAD within the past 3 years were recruited from 6 Canadian cardiac hospitals. Participants completed questionnaires assessing socio-demographics, comorbidities, and validated psychological measures, including Patient Health Questionnaire-9 (PHQ-9) for depression, Generalized Anxiety Disorder-7 (GAD-7) for generalized anxiety, Cardiac Anxiety Questionnaire (CAQ) for cardiac-related anxiety, and PTSD Checklist (PCL-5) for PTSD symptoms. Differences in mental health outcomes between SCAD survivors with and without FMD were analyzed using t-tests for continuous variables and chi-square tests for categorical variables. Results: The study included 326 participants (92.9% female; mean age 53.3 years), with 67 participants (20.6%) having a confirmed diagnosis of FMD at the time of questionnaire completion (39.3% FMD at study completion). Post-SCAD, patients with FMD reported significantly higher scores than patients without FMD on the GAD-7 (6.4±5.9 vs. 4.7±4.9, p = .028), CAQ (29.9±13.1 vs. 26.0±12.3, p = .023), and PCL-5 (17.2±15.4 vs. 13.3± 14.0, p = .048). The proportion of SCAD survivors with FMD scoring in the clinically diagnostic range was significantly higher than those in patients without FMD: 32.8% vs. 20.8% for depression, 31.3% vs. 17.4% for anxiety, 64.2% vs. 49.2% for cardiac anxiety, and 25.4% vs. 11.6% for PTSD (all p < .05). Conclusions: Our findings suggest that SCAD survivors with comorbid FMD experience significantly higher distress —depression, generalized anxiety, cardiac-related anxiety, and PTSD symptoms—compared to those without FMD. Longitudinal research is needed to explore the role of these mental health concerns in long-term mental health and cardiac outcomes. Enhanced psychological interventions for those with FMD may be required.

Abstract Aims This study aims to investigate the prognostic role of Stage 3 and 4 cardiac damage (CD) after transcatheter aortic valve intervention (TAVI), dependent on whether comorbidities contributing to right heart dysfunction were present. Methods and results Patients with severe aortic stenosis (AS) undergoing TAVI were included. Patients were divided into three groups: Stage 0–2 CD; Stage 3–4 CD, isolated AS (Stage 3–4 CD without significant concomitant chronic obstructive pulmonary disease, mitral annular calcification, mitral stenosis, mitral regurgitation, previous coronary artery bypass graft surgery, or cardiac amyloidosis); Stage 3–4 CD, AS with comorbidities (Stage 3–4 CD with ≥ 1 of these comorbidities). Futility was defined as death or Stage 3–4 New York Heart Association class dyspnoea 1 year after TAVI. Of 985 included patients, 822 (83%) had Stage 1–2 CD; 101 (10%) had Stage 3–4 CD, isolated AS; and 62 (6%) had Stage 3–4 CD, AS with comorbidities. Futility was not more common in Stage 3–4 CD groups (Stage 1–2 CD, 10%; Stage 3–4 CD, isolated AS, 17%; Stage 3–4 CD, AS with comorbidities, 15%, P = 0.09). Baseline and 1-year NYHA class were higher in Stage 3–4 CD compared with Stage 1–2 CD (P &lt; 0.01). The 6 min walking test distance increased similarly in all groups at 1 year. Conclusion Potential comorbidities contributing to right heart dysfunction were common among patients in Stage 3–4 CD undergoing TAVI. Stage 3–4 CD was not associated with a significantly higher risk of futility, irrespective of comorbidities, and they experienced a similar functional improvement after TAVI.

Background: Patients with non-English Language Preference are at risk of adverse health outcomes, particularly at end of life and during serious illness. Medical interpreters often feel unprepared to interpret conversations about serious illness. Best practice guidelines recommend a pre-encounter huddle between clinician and interpreter to better prepare both providers. The CHECK-IN (Check in for Exchange of Clinical and Key Information) guide is a simple communication tool designed to facilitate this pre-encounter huddle. We describe the results of a pilot feasibility study of the CHECK-IN guide performed in a simulation environment. The primary objectives of the study were to evaluate the feasibility, acceptability, and preliminary performance of the CHECK-IN guide. Methods: This U.S.-based study is a single-center simulation-based nonblinded randomized pilot feasibility study. Participating clinicians were randomized to usual practice (control) vs. introduction to the CHECK-IN guide (intervention). Clinicians completed pre- and post-session surveys. Participating clinicians were evaluated using the Faculty Observation Rating Scale (FORS), Interpreter Scale (IS), and Interpreter Impact Rating Scale (IIRS). Results: Participants had a highly favorable opinion on the acceptability, appropriateness, and feasibility of the CHECK-IN tool; 91% of participants agreed/strongly agreed on the acceptability of the tool, 91% agreed/strongly agreed on the appropriateness of the tool, and 100% agreed/strongly agreed on the feasibility of the tool. There were no statistical differences between control and intervention groups for the IS, IIRS, and FORS scores. Conclusion: The CHECK-IN guide is a promising tool to guide a pre-encounter huddle between clinician and interpreter, thereby improving interpreter-mediated communication when having conversations about serious illness.