Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2.

BackgroundIn the BOLERO-2 trial, everolimus (EVE), an inhibitor of mammalian target of rapamycin, demonstrated significant clinical benefit with an acceptable safety profile when administered with exemestane (EXE) in postmenopausal women with hormone receptor-positive (HR(+)) advanced breast cancer. We report on the incidence, time course, severity, and resolution of treatment-emergent adverse events (AEs) as well as incidence of dose modifications during the extended follow-up of this study.Patients and methodsPatients were randomized (2:1) to receive EVE 10 mg/day or placebo (PBO), with open-label EXE 25 mg/day (n = 724). The primary end point was progression-free survival. Secondary end points included overall survival, objective response rate, and safety. Safety evaluations included recording of AEs, laboratory values, dose interruptions/adjustments, and study drug discontinuations.ResultsThe safety population comprised 720 patients (EVE + EXE, 482; PBO + EXE, 238). The median follow-up was 18 months. Class-effect toxicities, including stomatitis, pneumonitis, and hyperglycemia, were generally of mild or moderate severity and occurred relatively early after treatment initiation (except pneumonitis); incidence tapered off thereafter. EVE dose reduction and interruption (360 and 705 events, respectively) required for AE management were independent of patient age. The median duration of dose interruption was 7 days. Discontinuation of both study drugs because of AEs was higher with EVE + EXE (9%) versus PBO + EXE (3%).ConclusionsMost EVE-associated AEs occur soon after initiation of therapy, are typically of mild or moderate severity, and are generally manageable with dose reduction and interruption. Discontinuation due to toxicity was uncommon. Understanding the time course of class-effect AEs will help inform preventive and monitoring strategies as well as patient education.Trial registration numberNCT00863655

Deposition of fluoride on enamel surfaces released from varnishes is limited to vicinity of fluoridation site

The aim of the in-situ study was to determine fluoride uptake in non-fluoridated, demineralized enamel after application of fluoride varnishes on enamel samples located at various distances from the non-fluoridated samples. All enamel samples used were demineralized with acidic hydroxyethylcellulose before the experiment. Intra-oral appliances were worn by ten volunteers in three series: (1, Mirafluorid, 0.15% F; 2, Duraphat, 2.3% F and 3, unfluoridated controls) of 6 days each. Each two enamel samples were prepared from 30 bovine incisors. One sample was used for the determination of baseline fluoride content (BFC); the other was treated according to the respective series and fixed in the intra-oral appliance for 6 days. Additionally, from 120 incisors, each four enamel samples were prepared (one for BFC). Three samples (a–c) were placed into each appliance at different sites: (a) directly neighboured to the fluoridated specimen (=next), (b) at 1-cm distance (=1 cm) and (c) in the opposite buccal aspect of the appliance (=opposite). At these sites, new unfluoridated samples were placed at days 1, 3 and 5, which were left in place for 1 day. The volunteers brushed their teeth and the samples with fluoridated toothpaste twice per day. Both the KOH-soluble and structurally bound fluoride were determined in all samples to determine fluoride uptake and were statistically analyzed. One day, after fluoridation with Duraphat, KOH-soluble fluoride uptake in specimen a (=next) was significantly higher compared to the corresponding samples of both the control and Mirafluorid series, which in turn were not significantly different from each other. At all other sites and time points, fluoride uptake in the enamel samples were not different from controls for both fluoride varnishes. Within the first day after application, intra-oral-fluoride release from the tested fluoride varnish Duraphat leads to KOH-soluble fluoride uptake only in enamel samples located in close vicinity to the fluoridation site

Evaluation of fluoride release from experimental TiF4 and NaF varnishes in vitro

Fluoride varnishes play an important role in the prevention of dental caries, promoting the inhibition of demineralization and the increase of remineralization. OBJECTIVE: This study aimed to analyze the amount of fluoride released into water and artificial saliva from experimental TiF(4 )and NaF varnishes, with different concentrations, for 12 h. MATERIAL AND METHODS: Fluoride varnishes were applied on acrylic blocks and then immersed in 10 ml of deionized water and artificial saliva in polystyrene bottles. The acrylic blocks were divided in seven groups (n=10): 1.55% TiF(4 )varnish (0.95% F, pH 1.0); 3.10% TiF(4 )varnish (1.90% F, pH 1.0); 3.10% and 4% TiF(4 )varnish (2.45% F, pH 1.0); 2.10% NaF varnish (0.95% F, pH 5.0); 4.20% NaF varnish (1.90% F, pH 5.0); 5.42% NaF varnish (2.45% F, pH 5.0) and control (no treatment, n=5). The fluoride release was analyzed after 1/2, 1, 3, 6, 9 and 12 h of exposure. The analysis was performed using an ion-specific electrode coupled to a potentiometer. Two-way ANOVA and Bonferroni's test were applied for the statistical analysis (p<0.05). RESULTS: TiF(4 )varnishes released larger amounts of fluoride than NaF varnishes during the first 1/2 h, regardless of their concentration; 4% TiF(4) varnish released more fluoride than NaF varnishes for the first 6 h. The peak of fluoride release occurred at 3 h. There was a better dose-response relationship among the varnishes exposed to water than to artificial saliva. CONCLUSIONS: The 3.10% and 4% TiF(4 )-based varnishes have greater ability to release fluoride into water and artificial saliva compared to NaF varnish; however, more studies must be conducted to elucidate the mechanism of action of TiF(4 )varnish on tooth surface

Back to the past: the individual and its role in creativity in organisations

O objetivo deste texto é realçar o papel do indivíduo na criatividade nas organizações. Esse papel tem sido estranhamente remetido para um plano secundário, à medida que as modernas visões da criatividade a definem, sobretudo, com relação ao contexto em que ocorre. De fato, na perspectiva atual, a criatividade não pode ser entendida sem se considerarem os contextos funcional, relacional e organizacional nos quais está inserido o trabalhador. Tais são as considerações da maior parte dos autores que escreve sobre o tópico, como sejam Amabile (1996), Csikszentmihalyi (1996), ou, mais recentemente, Glăveanu (2010a, 2010b). Essa corrente dominante, com origem no interacionismo psico-social, tem ainda influenciado o desenvolvimento teórico de outros conceitos em psicologia, sociologia, e, na sequência, nas ciências sociais e humanas, e na gestão. Essa supremacia no que concerne a criatividade, tem conduzido os autores a olvidar o papel do indivíduo no processo e no resultado criativos, chegando a retirar-lhe a responsabilidade e o protagonismo pela geração e produção de ideias. Desse modo, no presente texto, recuperam-se os argumentos em favor da centralidade da pessoa na criatividade, defendendo-se que esta tem uma existência isolada de influências externas, e que, como tal, devem relembrar-se as bases individuais da criatividadeThe goal of the current text is to highlight the role of the individual in creativity in organisations. This role has been strangely disregarded in recent years, as modern accounts of creativity have been emphasising the idea that creativity is only defined in context. This main stream argues that creativity is a process that essentially occurs within a functional, relational, and organisational context in which workers are inserted. Key authors defending such a position include the likes of Amabile (1996), Csikszentmihalyi (1996), and, more recently, Glăveanu (2010a, 2010b). This is a vision rooted in the psychosocial interactionist perspective, which has also had a considerable impact in other areas in psychology, sociology, management and other social and human sciences. This supremacy, with regards to creativity, has led many to forget the role of the individual person in the creative process and output, removing their responsibility and protagonism for generating and producing ideas. Hence, the current text intends to bring back to discussion the individual bases of creativity, that people can have an existence isolated from external influences, further defending that the concept can and should be defined out of context, rather than in contextinfo:eu-repo/semantics/publishedVersio

A RAPTOR ROADSIDE SURVEY IN WESTERN TURKEY AND EASTERN GREECE

Volume: 28Start Page: 186End Page: 19

Observations of nesting prairie falcons in the Los Padres National Forest

Volume: 18Start Page: 31End Page: 3