BACKGROUND: Utilization of ivabradine in the pediatric population has been centered on the goal of chronotropic control in patients with arrhythmias and heart failure. Tachycardia is known to be detrimental when it impai...BACKGROUND: Utilization of ivabradine in the pediatric population has been centered on the goal of chronotropic control in patients with arrhythmias and heart failure. Tachycardia is known to be detrimental when it impairs hemodynamics by increasing myocardial oxygen demand, increasing ventricular end-diastolic pressures, and decreasing cardiac output in certain patients. The acute hemodynamic effects of ivabradine have not yet been studied in real time. STUDY QUESTION: This study was performed leveraging the Sickbay platform (Medical Informatics Company, Houston, TX). The primary aim of this study was to characterize the effect of enteral ivabradine on heart rate in patients in a pediatric cardiac intensive care unit within 24 hours of initiation. Secondary aims were to characterize the effects of ivabradine on arterial saturation, respiratory rate, mean arterial blood pressure, central venous pressure, and renal near infrared spectroscopy for the same time frame. RESULTS: Heart rate decreased approximately 17% in the first 15 hours after ivabradine administration. Changes were seen in the secondary aims that varied depending on time after first and second doses. Specifically, decreases in central venous pressure and increased renal tissue oxygen saturation (rSO2) were observed by the end of the 24 hours. CONCLUSIONS: Ivabradine seems safe in pediatric patients. It is associated with 3 distinct hemodynamic response phases: the first phase is associated with decreased heart rate and unchanged systemic oxygen delivery, the second phase is associated with increased heart rate and worsened systemic oxygen delivery, and the third phase being associated with decreased heart rate and improved systemic oxygen delivery. These phases coincide with the pharmacokinetic properties of ivabradine.
BACKGROUND: The safety and efficacy of direct oral anticoagulants (DOACs) in patients with left ventricular assist devices (LVADs) remain uncertain because of limited comparative data with warfarin. STUDY QUESTION: Are D...BACKGROUND: The safety and efficacy of direct oral anticoagulants (DOACs) in patients with left ventricular assist devices (LVADs) remain uncertain because of limited comparative data with warfarin. STUDY QUESTION: Are DOACs a safe and effective alternative to warfarin in patients with durable LVADs? STUDY DESIGN: A retrospective cohort study using the TriNetX database was conducted. Adults with LVADs prescribed DOACs or warfarin were included. Propensity score matching (1:1) was performed to balance baseline characteristics. MEASURES AND OUTCOMES: The primary outcome was all-cause mortality. Secondary outcomes included thromboembolic events, major bleeding, and blood transfusion requirements. RESULTS: Among 3726 patients with LVAD, 79 received DOACs and 3647 received warfarin. After matching, 77 patients remained in each group. At 5 years, all-cause mortality was significantly lower in the DOAC group compared to warfarin (13% vs. 30%, P < 0.001). Rates of thromboembolism and major bleeding were similar, while blood transfusion needs were lower in the DOAC group (13% vs. 22.1%). CONCLUSIONS: In this multicenter cohort, DOACs were associated with improved long-term survival and comparable safety outcomes relative to warfarin in LVAD patients. These findings suggest DOACs may be a viable alternative, but larger prospective studies are warranted.
BACKGROUND: 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), also officially known as mebufotenin, is a naturally occurring serotonergic psychedelic alkaloid found in the venom of the Sonoran Desert toad ( Incilius alvarius...BACKGROUND: 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), also officially known as mebufotenin, is a naturally occurring serotonergic psychedelic alkaloid found in the venom of the Sonoran Desert toad ( Incilius alvarius ) and various plant species. AREAS OF UNCERTAINTY: Trace levels of 5-MeO-DMT may be produced endogenously in humans, but its physiologic role remains unclear. Safety profiles indicate low risk in controlled settings, though longer-term follow-ups with human subjects may be needed. Phenomenological overlaps with near-death experiences are noted but debated. THERAPEUTIC ADVANCES: Clinical trials have demonstrated rapid antidepressant effects. Top-line data from a recent phase 2b trial showed that 57.5% of participants remitted from treatment-resistant depression within 8 days. Other phase 2a and 2b trials have provided further, though still preliminary, evidence that 5-MeO-DMT may reduce depressive symptoms more than existing pharmacologic treatments, like selective serotonin reuptake inhibitors. LIMITATIONS: Most studies are early phase with small samples (n ≤193). Only 2 double-blind randomized controlled trials (RCTs) have been conducted in clinical populations, and long-term effects require further investigation. CONCLUSIONS: Emerging evidence supports 5-MeO-DMT as a promising, ultra-short-acting psychedelic for treatment-resistant depression and other psychiatric conditions, warranting larger RCTs.
BACKGROUND: Direct oral anticoagulants (DOACs) are widely used in patients with atrial fibrillation and venous thromboembolism. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently coprescribed in this population...BACKGROUND: Direct oral anticoagulants (DOACs) are widely used in patients with atrial fibrillation and venous thromboembolism. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently coprescribed in this population due to comorbid musculoskeletal or inflammatory conditions. However, the combined use of DOACs and NSAIDs is associated with an increased risk of bleeding due to additive pharmacodynamic effects and potential pharmacokinetic interactions. AREA OF UNCERTAINTY: Although the bleeding risk of this drug combination is well-recognized, evidence-based strategies to mitigate such risk remain limited. Current clinical guidelines do not offer detailed, stratified recommendations based on specific NSAID classes, individual DOAC agents, or particular high-risk populations such as elderly patients, individuals with cancer, those with chronic kidney disease, or patients with autoimmune disorders requiring prolonged NSAID therapy. In addition, the clinical relevance of pharmacokinetic interactions involving CYP3A4 and P-glycoprotein (P-gp), which may influence both DOAC and NSAID metabolism, remains insufficiently explored in real-world settings. DATA SOURCES: We conducted a structured literature search across PubMed/MEDLINE, Scopus, and Web of Science from January 2005 to December 2024 using the terms "direct oral anticoagulants," "NSAIDs," "bleeding," "drug interactions," and related MeSH headings. We included pharmacological studies, randomized trials, real-world cohort analyses, narrative reviews, and meta-analyses. Articles were screened by title and abstract, with full-text assessment for eligibility. THERAPEUTIC ADVANCES: The concomitant use of NSAIDs and direct oral anticoagulants (DOACs) presents a well-recognized bleeding risk due to their synergistic effects on platelet function and gastrointestinal mucosa integrity. However, the clinical message should not be a blanket prohibition of NSAID use in anticoagulated patients. However, careful and judicious use, at the lowest effective dose and for the shortest necessary duration, should be considered in select clinical situations.
BACKGROUND: Acute myocardial infarction (MI) is associated with a high incidence of morbidity and mortality. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic medications known for their favorable effect...BACKGROUND: Acute myocardial infarction (MI) is associated with a high incidence of morbidity and mortality. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic medications known for their favorable effects on cardiovascular disease. However, evidence regarding their effects in acute MI is limited. STUDY QUESTION: Whether early administration of dapagliflozin could affect the cardiovascular outcome of patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). STUDY DESIGN: We randomly allocated 101 patients with nondiabetes, nonheart failure STEMI undergoing primary PCI to receive dapagliflozin (10 mg/d started before PCI and continued for 40 days) or placebo. MEASURES AND OUTCOMES: The primary outcomes were changes in left ventricular ejection fraction (LVEF) 40 days after PCI, changes in cardiac troponin I (cTnI) levels, estimated infarct size using the peak and area under the curve (AUC) of cTnI, and ST-segment resolution. Secondary outcomes included high-sensitivity C-reactive (hs-CRP) protein levels at discharge and health-related quality of life (HRQoL) 40 days after acute MI. RESULTS: The results revealed a significant increase in LVEF in dapagliflozin-treated patients with baseline LVEF ≤40% compared with the placebo group (41.1 ± 5.5 vs. 38.1 ± 6.9; P = 0.037). No significant difference was observed regarding ST-segment resolution, cTnI levels, AUC, and peak between the 2 groups. We did not observe a significant difference regarding secondary outcomes. CONCLUSIONS: This study showed that dapagliflozin could significantly improve LVEF among patients whose LVEF dropped to ≤40% post-STEMI. However, further studies are required to confirm the study findings.
McLindon LA, Ried K, Wauchope B
… +3 more, Murnane L, Harradine E, Seman J
Am J Ther
· 2026 Mar-Apr 01 · PMID 41693032
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BACKGROUND: In 2020, COVID-19 caused by the SARS-CoV-2 emerged as a global pandemic. Combination therapies for viral illnesses may be more effective than single-agent therapies in reducing symptoms and preventing disease...BACKGROUND: In 2020, COVID-19 caused by the SARS-CoV-2 emerged as a global pandemic. Combination therapies for viral illnesses may be more effective than single-agent therapies in reducing symptoms and preventing disease progression. Repurposed drugs may offer cost-effective accessible treatment options while other novel therapies are being developed. STUDY QUESTION: To assess the safety and tolerability of a combination of repurposed drugs and supplements in the early therapy of acute nonhospitalized COVID-19 illness. STUDY DESIGN: A multicenter pilot cohort study was undertaken. Participants older than 40 years and positive for COVID-19 within 4 days of illness onset received telehealth outpatient care. The multimodal therapy of ivermectin, doxycyline, zinc, vitamin C, and vitamin D 3 was given as core therapy (group-1), or core therapy plus famotidine (group-2) for 10 days in a randomized masked controlled fashion. MEASURES AND OUTCOMES: A total of 275 participants, who were either vaccinated (n = 151) or unvaccinated (n = 124) for COVID-19, were randomized into group-1 (n = 137) or group-2 (n = 138). Four participants (1.5%) were hospitalized within the first 28 days. RESULTS: No viral rebound was experienced by any participants who took the 10-day therapy. Symptoms were reported daily until day 10, and at days 14, 28, and 90. The addition of famotidine resulted in less fatigue and nasal symptoms at day 14. These 5-component and 6-component interventions (ie, core therapy with and without famotidine) were equally safe and well tolerated. CONCLUSIONS: The multimodal therapy for acute COVID-19 was safe and well tolerated. The results justify adequately powered trials of the 5- or 6-component intervention on major early and late outcomes of COVID-19 infections.