Ribavirin has been shown to have broad-spectrum antiviral activity. To study its tissue distribution and disappearance rate, a single dose of 10 mg/kg which contained 10 ,uCi of ['4C]ribavirin was injected intravenously into rhesus monkeys and intramuscularly into monkeys and rats. Except for peak plasma concentrations and the initial phases of the plasma disappearance and urine excretion curves, no significant difference was observed between plasma, tissue, or urine values for intramuscularly or intravenously injected monkeys. Plasma disappearance curves were triphasic; plasma concentrations of ribavirin were similar for both monkeys and rats. Rats excreted ribavirin in the urine more rapidly and to a greater extent (82% excreted in 24 h) than did monkeys (60% excreted in 72 h). In the rat, only 3% of the injected ['40]ribavirin was detected in expired C02. Therefore, for both species, urine was the major route for the elimination of labeled ribavirin and its metabolites from the body. In monkeys, the amount of parent drug in blood cells increased through 48 h and remained stable for 72 h, whereas in rats, ribavirin decreased at a rate similar to the plasma disappearance curve. Concentrations of ribavirin at 8 h were consistently higher in monkeys than in rats for all tissues except the brain. Thus, these differences in blood cellular components and organ content and in urine excretion suggested that there was greater tissue retention of ribavirin in monkeys than in rats.

Aims  In the last decade, transcatheter aortic valve (TAV) replacement determined a paradigm shift in the treatment of patients with severe symptomatic aortic stenosis. Data on long-term TAV performance are still limited. We sought to evaluate the clinical and haemodynamic outcomes of the CoreValve self-expandable valve up to 8-year follow-up (FU). Methods and results  Nine hundred and ninety inoperable or high-risk patients were treated with the CoreValve TAV in eight Italian Centres from June 2007 to December 2011. The median FU was 4.4 years (interquartile range 1.4–6.7 years). Longest FU reached 11 years. A total of 728 died within 8-year FU (78.3% mortality from Kaplan–Meier curve analysis). A significant functional improvement was observed in the majority of patients and maintained over time, with 79.3% of surviving patients still classified New York Heart Association class ≤ II at 8 years. Echocardiographic data showed that the mean transprosthetic aortic gradient remained substantially unchanged (9 ± 4 mmHg at discharge, 9 ± 5 mmHg at 8 years, P = 0.495). The rate of Grade 0/1 paravalvular leak was consistent during FU with no significant change from post-procedure to FU ≥5 years in paired analysis (P = 0.164). Structural valve deterioration (SVD) and late bioprosthetic valve failure (BVF) were defined according to a modification of the 2017 EAPCI/ESC/EACTS criteria. In cumulative incidence functions at 8 years, moderate and severe SVD were 3.0% [95% confidence interval (CI) 2.1–4.3%] and 1.6% (95% CI 0.6–3.9%), respectively, while late BVF was 2.5% (95% CI 1.2–5%). Conclusion  While TAVs are questioned about long-term performance and durability, the results of the present research provide reassuring 8-year evidence on the CoreValve first-generation self-expandable bioprosthesis.

Among the many impacts of the COVID-19 pandemic, one of the most dramatic was the immediate closure of in-person schooling when parents were faced with much greater responsibility in supporting their children’s learning. Despite this, few studies have examined parents’ own perspectives of this experience. The aims of this study were to (1) identify overall challenges, benefits, and useful strategies related to home learning and (2) examine differences in findings across continents, between parents of youth with and without attention-deficit/hyperactivity disorder (ADHD), and between parents of children and adolescents. A qualitative approach was used to understand parents’ responses to remote learning across three studies conducted in the United States and Australia. Parents (N=606, children: 68.5% male, ages 6-17 years) provided responses to three open-ended questions. The most frequently expressed challenges were difficulty staying on task (20.5%), lack of motivation (15.3%), teacher-related factors such as poor teaching quality (13.4%), lack of social interaction opportunities (10.9%), and balancing parent work with online learning (10.2%). The most frequently expressed strategy related to using routines and schedules (51.4%) and the biggest benefit was more family time (18.3%). Findings were largely consistent across continents, ADHD status, and age, suggesting that many parental responses to remote learning appear to be universal. Given that the most common challenges were child- (e.g., difficulties with staying on task and motivation), parent- (e.g., balancing remote learning with work responsibilities), and teacher- (e.g., poor instructional quality) related, there is a need for improved support across these systems going forward.

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Aims: We aim at exploring whether severe chronic kidney disease (CKD) may modify the impact of acute kidney injury (AKI) post-transcatheter aortic valve implantation (TAVI) on early, mid, and long-term mortality. Methods and results: The analysis included 2,733 TAVI patients from the Italian Clinical Service Project. The population was stratified in four groups according to the presence of baseline severe CKD and postprocedural AKI. All-cause mortality was the primary end point. Postprocedural AKI is associated with an increased risk of early and mid-term mortality after TAVI regardless of baseline severe CKD. Preprocedural severe CKD is associated with an increased risk of long-term mortality after TAVI regardless of postprocedural AKI. No interaction between preprocedural severe CKD and postprocedural AKI was observed in predicting mortality at both 30-day