Search

Background Daptomycin stands as a key IV antibiotic in treating MRSA infections. However, patients facing challenges with difficult venous access require alternative administration routes. This study aimed to evaluate the pharmacokinetic (PK) profile and safety of subcutaneous (SC) daptomycin. Patients and methods In a two-period, two-treatment, single-blind crossover Phase I trial (ClinicalTrials.gov NCT04434300), participants with no medical history received daptomycin (10 mg/kg) both IV and SC in a random order, with a minimum 2 week washout period together with matched placebo (NaCl 0.9%). Blood samples collected over 24 h facilitated PK comparison. Monte Carlo simulations assessed the PTA for various dosing regimens. Adverse events were graded according to Common Terminology Criteria for Adverse Events(CTCAE) v5.0. Results Twelve participants (aged 30.9 ± 24.4 years; 9 male,75%) were included. SC daptomycin exhibited delayed (median T max 0.5 h for IV versus 4 h for SC) and lower peak concentration than IV (C max = 132.2 ± 16.0 μg/mL for IV versus 57.3 ± 8.6 μg/mL for SC; P  < 0.001). SC AUC0–24 (937.3 ± 102.5 μg·h/mL) was significantly lower (P  = 0.005) than IV AUC0–24 (1056.3 ± 123.5 μg·h/mL) but was deemed bioequivalent. PTA demonstrated target AUC0–24 attainment for 100% of simulated individuals, for both 8 and 10 mg/kg/24 h SC regimens. Adverse events (AEs) related to SC daptomycin were more frequent than for SC placebo (25 versus 13, P  = 0.016). No serious AEs were reported. Conclusions Single-dose SC daptomycin infusion proved to be safe, exhibiting a bioequivalent AUC0–24 compared with the IV route. The SC route emerges as a potential and effective alternative when IV administration is not possible. [ABSTRACT FROM AUTHOR]

Background: Borderline Personality Disorder (BPD) is a prevalent and debilitating psychiatric condition often accompanied by Post-Traumatic Stress Disorder (PTSD), with a substantial prevalence of trauma history among affected individuals. The clinical, cognitive, and cerebral parallels shared with PTSD suggest a trauma-related etiology for BPD. Studies consistently demonstrate a reduction in hippocampal volume in individuals with BPD, echoing findings in PTSD. However, the interpretation of this shared neurobiological profile remains contentious, with ongoing debates regarding the independence of these pathologies or the potential exacerbation of diminished hippocampal volume in BPD due to concurrent PTSD. Differential impacts on hippocampal subfields across both disorders may further complicate interpretation, suggesting the volume of hippocampal subfields as a potential discriminant biomarker. This study aims to characterize the multidimensional specific and shared profiles of BPD and PTSD-related alterations, with a particular emphasis on hippocampal subfields during adolescence, a crucial period in BPD development. Methods: This study focuses on female adolescents, who are more prevalent in the BPD population. Participants are categorized into three groups: BPD, BPD with comorbid PTSD, and a control group of matched healthy individuals. Data collection encompasses clinical, cognitive, and neuroimaging domains commonly affected in both disorders, utilizing various imaging markers (including gray matter macrostructure, white matter microstructural integrity, and regional functional connectivity). Discussion: This study examines adolescent BPD with and without comorbid PTSD on clinical, neuroimaging, and cognitive levels. It is the first to use a comprehensive multi-modal approach within the same sample. Additionally, it uniquely explores hippocampal subfield volume differences in adolescents. Analysis of the relationship between the investigated domains and the effects of PTSD comorbidity will elucidate specific and shared alteration profiles in both disorders. Trial registration: IDRCB number 2019-A00366-51 / ID: NCT0485274. Registered on 21/04/2021. [ABSTRACT FROM AUTHOR]

This article discusses the use of surrogate endpoints in evaluating the effectiveness of therapies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The authors present a systematic review and meta-analysis of randomized controlled trials (RCTs) on unvaccinated outpatients with COVID-19. They found that the reduction in nasopharyngeal viral load reliably predicted a reduction in the risk of hospitalization or death at the trial level. However, at the individual patient level, the relationship between viral load reduction and treatment effect was less clear. The authors conclude that nasopharyngeal viral load reduction remains a valuable surrogate endpoint in pandemic preparedness, but its validity should be considered preliminary and conditional. [Extracted from the article]

Introduction: Several randomised controlled trials have demonstrated that novel oral anticoagulants are safer compared with vitamin K antagonists for the management of non-valvular atrial fibrillation (NVAF) to prevent thromboembolic events in the general population. There is a growing interest in the use of apixaban in patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) but there is a lack of randomised data in this population., Methods and Analysis: APIDP2 is a prospective parallel, randomised, open-label, blinded endpoint trial involving patients with ESRD undergoing chronic PD who have NVAF. A total of 178 participants will be recruited from 20 French PD centres. Eligible patients will be randomly assigned to receive either apixaban at a reduced dose of 2.5 mg two times per day (dose determined with the previous pharmacokinetic study APIDP1) or dose-adjusted to international normalised ratio (INR) target (2-3) coumadin therapy. Anticoagulation to prevent thromboembolic events will be initiated or changed according to the randomisation for a duration of 1 year. The primary outcome is a major or clinically relevant non-major bleeding from randomisation up to month 12, assessed according to the International Society on Thrombosis and Haemostasis Score. Secondary outcomes encompass an efficacy composite criterion combining stroke or transient ischaemic attack (TIA), cardiovascular death and thrombosis including myocardial infarction cumulated at 12 months. Bleeding events will be also classified according to Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) and Thrombolysis In Myocardial Infarction (TIMI) criteria and pharmacodynamics outcomes will evaluate the time within the INR target range of 2-3 in the warfarin arm over 1 year, and anti-Xa apixaban activity in case of bleeding events and at 1 month, 6 months and 12 months of follow-up in the apixaban arm. To demonstrate that apixaban is safer than warfarin at 1 year, assuming two interim analyses after 60 and 118 patients, a bilateral alpha risk of 5% and a power of 80%, 178 patients are needed in this randomised trial (effect size found from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Study among patients with creatinine clearance 25-30 ml/min), that is, 89 patients per group., Ethics and Dissemination: The study has been approved by the ethics committee Comité de Protection des Personnes Sud Est III - Lyon - FRANCE, CT number 2023-507544-37-00. Written informed consent is required for each participant. Findings will be presented at scientific meetings and published in peer-reviewed journals., Trial Registration: ClinicalTrials.gov, NCT06045858; European Clinical Trial System, CT number 2023-507544-37-00., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)