BACKGROUND AND AIMS:The TRISCEND II trial demonstrated superior clinical benefits for patients with ≥severe tricuspid regurgitation (TR) treated with the EVOQUE transcatheter tricuspid valve replacement (TTVR) system plus medical therapy vs medical therapy alone. This work reports 1-year and 18-month outcomes in patients stratified by baseline TR severity. METHODS:The multicentre, prospective TRISCEND II trial enrolled 400 patients with symptomatic, ≥severe TR, and randomized 2:1 to TTVR (n = 267) or control (n = 133). In a post hoc analysis, patients were stratified into severe TR (n = 172) and massive/torrential TR (n = 220) cohorts. Clinical and quality-of-life outcomes were reported at 1 year, with Kaplan-Meier estimates for all-cause mortality and heart failure (HF) hospitalization assessed at 18 months. Study oversight included an independent echocardiographic core laboratory, clinical events committee, and data safety monitoring board. RESULTS:One year after TTVR, TR was ≤mild in 95.2% of severe TR and 95.3% of massive/torrential TR patients. The primary safety and effectiveness endpoint (win ratio) favoured TTVR over control regardless of baseline TR severity: severe {1.64 [95% confidence interval (CI): 1.11, 2.43]} and massive/torrential [2.20 (1.55, 3.14)]. At 18 months, TTVR patients had similar mortality to controls [rate difference: severe 0.2% (-11.6, 11.9), massive/torrential -5.8% (-17.6, 6.0)], whereas HF hospitalization rates favoured TTVR in the massive/torrential cohort [vs control, severe 9.8% (-3.0, 22.7), massive/torrential -15.2% (-28.9, -1.5)]. CONCLUSIONS:Patients with ≥severe TR benefit from TTVR, experiencing improvements in TR severity, functional capacity, and quality of life regardless of baseline TR severity, with a signal for greater benefit in patients with more advanced disease.
PURPOSE:Cardiac rehabilitation (CR) could be an important opportunity for optimization of guideline-directed medical therapies (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF). We set out to describe GDMT prescribing among enrollees in CR with HFrEF. METHODS:We queried the electronic health record of an academic medical center and identified patients with HFrEF who attended CR between 2016 and 2023. We defined CR cycles as at least 6 CR sessions with fewer than 6 months between sessions. Using a validated algorithm, we generated medication optimization scores (MOS, 0%-100% optimized) at the first and final CR session. The algorithm's input included GDMT, New York Heart Association classification, systolic blood pressure, heart rate, creatinine, potassium, allergies, and race. Wilcoxon Signed-Rank analysis was used to compare MOS. RESULTS:A total of 172 CR cycles were completed by 152 patients (64% male, 78% White, 67.5 ± 12.1 years old). Mean sessions per CR cycle was 26.4 ± 10.6. At the end of CR, 85 (49%) patients were on a beta-blocker, 84 (49%) a renin-angiotensin-aldosterone inhibitor, and 31 (18%) a mineralocorticoid receptor antagonist. Accounting for contraindications, patients were eligible for initiation or uptitration of at least 1 GDMT class after 84% of cycles. Median MOS at the start of CR was 39% (IQR: 14, 57) and 35% (IQR: 14, 57) at the end of CR ( P = .90). CONCLUSION:GDMT utilization among patients with HFrEF in CR is suboptimal. There is a substantial opportunity to develop and validate strategies to improve GDMT prescribing during CR.
Background:Acute pancreatitis (AP) is without specific drug therapy. We conducted a phase 2b trial of the calcium release-activated calcium channel inhibitor zegocractin, previously found to accelerate recovery of food intake in AP, to determine dose-response, target population, endpoints, safety and tolerability in AP with systemic inflammatory response syndrome. Methods:This double-blind, randomised, placebo-controlled, phase 2b trial enrolled adults (aged ≥18 years) with AP and systemic inflammatory response syndrome at 37 centres in the US and India. Patients were randomly assigned (1:1:1:1) to receive placebo or 0.5 (low), 1.0 (medium) or 2.0 (high) mg per kilogramme intravenous zegocractin once daily for 3 days. The primary outcome was time to solid food tolerance, and all outcomes were specified a priori. This trial is registered with ClinicalTrials.gov (NCT04681066) and is complete. Findings:Between 30th March, 2021 and 16th April, 2024, 216 patients were assigned to placebo (N = 53), low (N = 53), medium (N = 56) or high (N = 54) dose zegocractin. The primary outcome of median time to solid food tolerance was 66, 78, 64, and 67 h in these groups respectively (n.s.). Dose-response was observed in patients with a high haematocrit (n = 92), the median times being 113.5, 78, 64 and 67 h, and in those with Balthazar D or E computed tomography at presentation (n = 145), at 112, 68.5, 68.5, and 66 h respectively. Overall, there were dose-dependent responses for the secondary outcomes new-onset severe respiratory failure (4, 4, 0, and 0 patients), new-onset necrotising pancreatitis (17, 17, 20 and 11 patients) and time to medically indicated discharge (104, 109.5, 104.5 and 89 median hours), reflected in an exploratory win ratio for high dose zegocractin compared to placebo of 1.640 (95% CI 1.030-2.612; p = 0.04). Interpretation:This trial was negative for the primary endpoint of time to solid food tolerance in the whole trial population but improvement with zegocractin was seen in patients with a high haematocrit or Balthazar score. Multiple secondary endpoints improved consistently with zegocractin compared to placebo, most notably in preventing new-onset severe respiratory failure. These findings identified a suitable dose, a potential patient population, and endpoints for a phase 3 trial. Funding:CalciMedica.
This systematic review (PROSPERO CRD420246206360) investigated relationships between self-reported or objective sleep duration and fluid biomarkers of Alzheimer's disease pathology and neurodegeneration: cerebrospinal fluid or blood Aβ, p-tau181, t-tau, NfL and GFAP. We searched PubMed, SCOPUS, and CINAHL from inception to September 2024. Twenty studies (n = 12,445) met inclusion criteria (13 cerebrospinal fluid biomarkers [n = 2836]; 7 blood biomarkers [n = 9609]). Study quality was assessed using Newcastle-Ottawa scales. Whereas many studies did not report any associations, some trends emerged: short sleep duration was associated with higher cerebrospinal fluid t-tau and p-tau181 and lower cerebrospinal fluid or blood Aβ42 across multiple studies. Longer sleep duration showed more variable associations, with some suggesting either worse or better biomarker profiles (e.g., higher and lower fluid t-tau, p-tau181, or Aβ42). Two studies investigating non-linear relationships identified U-shaped associations, suggesting both short (≤5-6 h) and long (≥8 h) sleep durations are associated with altered biomarker profiles. The predominantly cross-sectional and high heterogeneity of the available evidence, as well as the relatively small number of studies by individual biomarker (especially for NfL and GFAP) limit conclusions about sleep-biomarker relationships. Future research should investigate emerging blood-based biomarkers and explore temporal associations between sleep duration and Alzheimer's disease biomarker changes.
Curriculum overload is a recognized challenge in pharmacy education, resulting in faculty and student inefficiencies, stress, and burnout. Although recent efforts have focused on addressing curriculum expansion and content overload, a related challenge has emerged: assessment overload. Assessment overload presents as a distinct yet interconnected phenomenon to curriculum overload, sharing similar causes and consequences for faculty and students. This commentary explores faculty and student perspectives and proposes 2 strategies for addressing assessment overload. These strategies include integrating mindful assessment evaluation into pre-existing course continuous quality improvement efforts and conducting an intentional review of assessments. With a focus on alignment, intention, and balance, these approaches offer mechanisms to reduce unnecessary assessment burdens while preserving meaningful evaluations of learning. Collaborative efforts within courses, across institutions, and across the Academy can support the development of intentional, sustainable assessment practices that better serve faculty and students.
