Search

Background Preserving health-related quality of life (HRQOL) is an important goal during renal cell carcinoma treatment. We report HRQOL outcomes from a phase II trial (NCT03173560). Patients and Methods HRQOL data were collected during a multicenter, randomized, open-label phase II study comparing the safety and efficacy of 2 different starting doses of lenvatinib (18 mg vs. 14 mg daily) in combination with everolimus (5 mg daily), following one prior vascular endothelial growth factor–targeted treatment. HRQOL was measured using 3 different instruments—FKSI-DRS, EORTC QLQ-C30, and EQ-5D-3L—which were all secondary endpoints. Change from baseline was assessed using linear mixed-effects models. Deterioration events for time to deterioration (TTD) analyses were defined using established thresholds for minimally important differences in the change from baseline for each scale. TTD for each treatment arm was estimated using the Kaplan–Meier method. Results Baseline characteristics of the 343 participants randomly assigned to 18 mg lenvatinib (n = 171) and 14 mg lenvatinib (n = 172) were well balanced. Least-squares mean estimates for change from baseline were favorable for the 18 mg group over the 14 mg group for the FKSI-DRS and most EORTC QLQ-C30 scales, but differences between treatments did not exceed the minimally important thresholds. Median TTD was longer among participants in the 18 mg group than those in the 14 mg group for most scales. Conclusions Participants who received an 18 mg lenvatinib starting dose had favorable HRQOL scores and longer TTD on most scales compared with those who received a 14 mg starting dose.

Background: Lenvatinib (18 mg) plus everolimus (5 mg) is approved for patients with advanced renal cell carcinoma (RCC) after one or more prior antiangiogenic therapies. Objective: To assess whether a lower starting dose of lenvatinib has comparable efficacy with improved tolerability for patients with advanced RCC treated with lenvatinib plus everolimus. Design, setting, and participants: A randomized, open-label, phase 2 global trial was conducted in patients with advanced clear cell RCC and disease progression after one prior vascular endothelial growth factor–targeted therapy (prior anti–programmed death-1/programmed death ligand-1 therapy permitted). Intervention: Patients were randomly assigned 1:1 to the 14- or 18-mg lenvatinib starting dose, both in combination with everolimus 5 mg/d. Patients in the 14-mg arm were to be uptitrated to lenvatinib 18 mg at cycle 2, day 1, barring intolerable grade 2 or any grade ≥3 treatment-emergent adverse events (TEAEs) requiring dose reduction occurring in the first 28-d cycle. Outcome measurements and statistical analysis: The primary efficacy endpoint was investigator-assessed objective response rate (ORR) as of week 24 (ORRwk24); the noninferiority threshold of the 14- versus 18-mg arm was p ≤ 0.045. The primary safety endpoint was the proportion of patients with intolerable grade 2 or any grade ≥3 TEAEs within 24 wk of randomization. Results and limitations: The ORRwk24 for the 14-mg arm (32% [95% confidence interval {CI} 25–39]) was not noninferior to the ORRwk24 in the 18-mg arm (35% [95% CI 27–42]; odds ratio: 0.88; 90% CI 0.59–1.32; p = 0.3). The proportion of intolerable grade 2 or any grade ≥3 TEAEs was similar between the two arms (14 mg, 83% vs 18 mg, 80%; p = 0.5). The secondary endpoints of overall ORR, progression-free survival, and overall survival numerically favored the 18-mg arm. A limitation of this study was that the study design did not allow for a full comparison of progression-free survival between treatment arms. Conclusions: The study findings support the approved dosing regimen of lenvatinib 18 mg plus everolimus 5 mg daily for patients with advanced RCC. Patient summary: In this report, we examined two doses of lenvatinib (the approved 18-mg dose and a lower dose of 14 mg) in people with advanced renal cell carcinoma to determine whether the lower dose (which was increased to the approved 18-mg dose after the first treatment cycle) could improve safety without affecting efficacy. The results showed that the efficacy of the lower lenvatinib dose (14 mg) was not the same as that of the approved (18 mg) dose, although safety results were similar, so the approved lenvatinib 18-mg dose should still be used. publishedVersion

Rationale and objectives Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that leads to an increased risk of emphysema and liver disease. Despite extensive investigation, there remain unanswered questions concerning the natural history, pathophysiology, genetics and the prognosis of the lung disease in association with AATD. The European Alpha-1 Clinical Research Collaboration (EARCO) is designed to bring together researchers from European countries and to create a standardised database for the follow-up of patients with AATD. Study design and population The EARCO Registry is a non-interventional, multicentre, pan-European, longitudinal observational cohort study enrolling patients with AATD. Data will be collected prospectively without interference/modification of patient's management by the study team. The major inclusion criterion is diagnosed severe AATD, defined by an AAT serum level, The EARCO Registry is a non-interventional, multicentre, pan-European, longitudinal observational cohort study enrolling patients with AATD to elucidate the natural history, pathophysiology, genetics and prognosis of this condition http://bit.ly/369ScCc

Alpha-1 antitrypsin deficiency (AATD) is one of the most frequent rare diseases in Europe and may result in serious lung disease and/or liver disease in adults. People with this condition have a much lower level than normal of the protective protein alpha-1 antitrypsin (AAT) in their blood. AAT protects the body from a powerful enzyme called neutrophil elastase. AATD is an inherited condition that is caused by mutations in the SERPINA1 gene, which can lead to a shortage of AAT or an abnormal form of the protein that cannot control neutrophil elastase. The SERPINA1 gene has more than 100 variants, coded for by two alleles (different versions of the same gene). PiMM is the normal allele, while PiMZ has one normal and one defective allele and PiZZ is the most common allele that causes AATD. The signs and symptoms of the condition and the age at which they appear vary significantly among individuals. The heterogeneity of the clinical picture of AATD depends on a variety of genetic and external aspects. Environmental factors, such as exposure to tobacco smoke, chemicals and dust, probably impact the severity of AATD-associated lung disease., Three people with alpha-1 antitrypsin deficiency (AATD) share their experiences of living with this rare, genetic condition. They reflect on living with AATD and its impact on their lives including inequality of access to treatment across Europe. https://bit.ly/3rrYS9s

Our study compared a flipped class with a standard lecture class in four introductory courses: finite mathematics, precalculus, business calculus, and calculus 1. The flipped sections watched video lectures outside of class and spent time in class actively working on problems. The traditional sections had lectures in class and did homework outside of class. No statistical difference was found in test scores of the students, though qualitative data indicated potential problems with implementing the flipped pedagogy. Specifically, many students had negative opinions of the flipped model, and attitudes toward math in general tended to decline, comparatively, for students in the flipped class.