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BACKGROUND: miniSTONE-2 (NCT03629184) was a global, phase 3, randomized, controlled study that investigated the safety and efficacy of single-dose baloxavir marboxil in otherwise healthy children 1-<12 years of age and showed a positive risk-benefit profile. This post hoc analysis evaluated the safety and efficacy of baloxavir versus oseltamivir in children 5-11 years old with influenza. METHODS: Children received single-dose baloxavir or twice-daily oseltamivir for 5 days. Safety was the primary objective. Efficacy and virological outcomes included time to alleviation of symptoms, duration of fever and time to cessation of viral shedding by titer. Data were summarized descriptively. RESULTS: Ninety-four children 5-11 years old were included (61 baloxavir and 33 oseltamivir). Baseline characteristics were similar between the groups. The incidence of adverse events was balanced and low in both treatment groups, with the most common being vomiting (baloxavir 5% vs. oseltamivir 18%), diarrhea (5% vs. 0%) and otitis media (0% vs. 5%). No serious adverse events or deaths occurred. Median (95% CI) time to alleviation of symptoms with baloxavir was 138.4 hours (116.7-163.4) versus 126.1 hours (95.9-165.7) for oseltamivir; duration of fever was comparable between groups [41.2 hours (23.5-51.4) vs. 51.3 hours (30.7-56.8), respectively]. Median time to cessation of viral shedding was shorter in the baloxavir group versus oseltamivir (1 vs. ≈3 days). CONCLUSIONS: Safety, efficacy and virological results in children 5-11 years were similar to those from the overall study population 1-<12 years of age. Single-dose baloxavir provides an additional treatment option for pediatric patients 5-11 years old with influenza.
RESUMEN
BERENICE (NCT02132949) assessed the cardiac safety of the neoadjuvant−adjuvant pertuzumab−trastuzumab-based therapy for high-risk, HER2-positive early breast cancer (EBC). We describe key secondary objectives at final analysis. Eligible patients received dose-dense doxorubicin and cyclophosphamide q2w × 4 â paclitaxel qw × 12 (Cohort A) or 5-fluorouracil, epirubicin, cyclophosphamide q3w × 4 â docetaxel q3w × 4 (B) as per physician's choice. Pertuzumab−trastuzumab (q3w) was initiated from the taxane start and continued post-surgery to complete 1 year. Median follow-up: 64.5 months. There were no new cardiac issues and a low incidence of Class III/IV heart failure (Cohort B only: one patient (0.5%) in the adjuvant and treatment-free follow-up (TFFU) periods). Fourteen patients (7.7%) had LVEF declines of ≥10% points from baseline to <50% in Cohort A, as did 20 (10.5%) in B during the adjuvant period (12 (6.2%) in A and 7 (3.6%) in B during TFFU). The five-year event-free survival rates in Cohorts A and B were 90.8% (95% CI: 86.5, 95.2) and 89.2% (84.8, 93.6), respectively. The five-year overall survival rates were 96.1% (95% CI: 93.3, 98.9) and 93.8% (90.3, 97.2), respectively. The final analysis of BERENICE further supports pertuzumab−trastuzumab-based therapies as standard of care for high-risk, HER2-positive EBC.
RESUMEN
The ring-opening polymerization (ROP) of lactide (the dilactone of lactic acid) produces poly(lactide) commonly referred to as poly(lactic acid) (PLA). The monomer lactide, has two stereogenic centers and thus, three stereoisomers are possible, namely: D-(R,R), L-(S,S) and meso-lactide. The rac-lactide is an equimolar mixture of D- and L-enantiomers. Depending upon the relative configuration of the stereogenic centers in the polymeric chain, different tacticities (isotactic, syndiotactic, heterotactic and atactic) arise in the PLA chains. The study of the tacticity of a polymer is fundamental since it plays a crucial role in determining the physical properties of the polymer. NMR spectroscopy is a powerful analytical technique for the determination of the tacticity of PLA. This article describes in details the tacticity assignment for PLA derived from ROP of rac-lactide and meso-lactide, using homonuclear proton-decoupled 1 H NMR. The detailed tetrad level assignment pertinent to the methine hydrogen signal is the key for the determination of tacticity.
