Undesirable events during electronic cigarette use prior to the implementation of Article 20 of the European Union Tobacco Products Directive: Findings from the EUREST-PLUS ITC Europe Surveys

Introduction: Article 20 of the European Union (EU) Tobacco Products Directive (TPD) sets forth provisions on electronic cigarette (e-cigarette) product regulation, such as child-proof packaging and protection against e-liquid refilling without leakage. The aim of the current study was to examine frequencies and correlates of experiencing undesirable events during e-cigarette use related to e-cigarette product design parameters prior to the implementation of the EU TPD. Material and Methods: The EUREST-PLUS ITC Europe Wave 1 survey was conducted with adult cigarette smokers from June to September 2016 across Germany, Greece, Hungary, Poland, Romania, Spain. Results: Among our sample of adult cigarette smokers, one in five reported having ever used e-cigarettes. Prevalence of current e-cigarette use (daily or weekly) was very low (1.5%). Major undesirable events, such as battery exploding or catching fire (1.9%) or overheating (11%) were uncommon. Among those reporting at least monthly use and whose usual/current brand has a tank that you fill with liquids, 18.8% experienced spilling during refill and 18.5% experienced e-liquid leaking during use. Nearly one-quarter reported that the e-liquid cap was easy for a child to open. Conclusions: In light of the EU TPD establishing standards around e-cigarette design parameters to mitigate undesirable events and risks during e-cigarette use, these findings further support the need for its implementation, as well as for monitoring undesirable events experienced during e-cigarette use once Article 20 is fully implemented

Perceptions, Predictors of and Motivation for Quitting among Smokers from Six European Countries from 2016 to 2018: Findings from EUREST-PLUS ITC Europe Surveys

The European Tobacco Products Directive (TPD) was introduced in 2016 in an effort to decrease prevalence of smoking and increase cessation in the European Union (EU). This study aimed to explore quitting behaviours, motivation, reasons and perceptions about quitting, as well as predictors (reported before the TPD implementation) associated with post-TPD quit status. A cohort study was conducted involving adult smokers from six EU countries (n= 3195). Data collection occurred pre-(Wave 1; 2016) and post-(Wave 2; 2018) TPD implementation. Bivariate and logistic regression analyses of weighted data were conducted. Within this cohort sample, 415 (13.0%) respondents reported quitting at Wave 2. Predictors of quitting were moderate or high education, fewer cigarettes smoked per day at baseline, a past quit attempt, lower level of perceived addiction, plans for quitting and the presence of a smoking-related comorbidity. Health concerns, price of cigarettes and being a good example for children were among the most important reasons that predicted being a quitter at Wave 2. Our findings show that the factors influencing decisions about quitting may be shared among European countries. European policy and the revised version of TPD could emphasise these factors through health warnings and/or campaigns and other policies

Quitting behaviors and cessation assistance used among smokers with anxiety or depression: Findings among six countries of the EUREST-PLUS ITC Europe Surveys

Introduction: The current study explores quitting behaviours and use of cessation assistance among adult tobacco users with probable anxiety or depression (PAD) and in six European (EU) Member States (MS). Material and Methods: The EUREST-PLUS ITC Wave 1 Europe Survey was conducted with a nationally representative cross-sectional sample of 6,011 adult cigarette smokers from six European Union (EU) Member States (MS) (Germany, Greece, Hungary, Poland, Romania, Spain) in 2016. Results: Our study found that one in five smokers sampled from six EU MS had a diagnosis, treatment or positive screen for anxiety or depression, with rates of PAD varying between EU MS. Results of the multivariable logistic regression analysis showed that respondents with PAD were more likely to have made a quit attempt in the last 12 months (AOR 1.75; 95%CI 1.45-2.11), compared to respondents without PAD. Among those respondents with PAD who used support the most frequently reported quit method was prescription-based quit smoking pharmacotherapy (15.4%) followed by e-cigarettes (13.7%) and NRT (11.3%). Person-to-person behavioral support (i.e. local quit services, face-to-face advice from a doctor or other health care professional, telephone or quitline services) was reported significantly more frequently among respondents with PAD compared to those without PAD. Conclusions: Given both pharmacological and non-pharmacological quit smoking aids have been shown to be safe, acceptable and effective for people with and without mental illness it is important that their use be promoted among smokers with anxiety and depression alongside behavioral counseling. Our findings support the need for interventions targeting health care professionals in providing smoking cessation assistance among this population of smokers

European adult smokers' perceptions of the harmfulness of e-cigarettes relative to combustible cigarettes: cohort findings from the 2016 and 2018 EUREST-PLUS ITC Europe Surveys

Background: This study presents perceptions of the harmfulness of electronic cigarettes (e-cigarettes) relative to combustible cigarettes among smokers from six European Union (EU) countries, prior to the implementation of the EU Tobacco Products Directive (TPD), and 2 years post-TPD. Methods: Data were drawn from the EUREST-PLUS ITC Europe Surveys, a cohort study of adult smokers (>= 18 years) from Germany, Greece, Hungary, Poland, Romania and Spain. Data were collected in 2016 (pre-TPD: N = 6011) and 2018 (post-TPD: N = 6027). Weighted generalized estimating equations were used to estimate perceptions of the harmfulness of e-cigarettes compared to combustible cigarettes (less harmful, equally harmful, more harmful or 'don't know'). Results: In 2016, among respondents who were aware of e-cigarettes (72.2%), 28.6% reported that they perceived e-cigarettes to be less harmful than cigarettes (range 22.0% in Spain to 34.1% in Hungary). In 2018, 72.2% of respondents were aware of e-cigarettes, of whom 28.4% reported perceiving that e-cigarettes are less harmful. The majority of respondents perceived e-cigarettes to be equally or more harmful than cigarettes in both 2016 (58.5%) and 2018 (61.8%, P>0.05). Overall, there were no significant changes in the perceptions that e-cigarettes are less, equally or more harmful than cigarettes, but 'don't know' responses significantly decreased from 12.9% to 9.8% (P = 0.036). The only significant change within countries was a decrease in 'don't know' responses in Spain (19.3-9.4%, P = .001). Conclusions: The majority of respondents in these six EU countries perceived e-cigarettes to be equally or more harmful than combustible cigarettes

Cigarette brand loyalty among smokers in six European countries - findings from the EUREST-PLUS ITC Survey

INTRODUCTION This study aims to describe the degree of smokers' loyalty to a specific brand of tobacco products and the variables related to choosing a specific brand among smokers in six European countries. METHODS A cross-sectional analysis was conducted for a representative sample of adult smokers from Germany, Greece, Hungary, Poland, Romania, and Spain (approximately 1000 smokers per country). The prevalence of smokers' having a usual brand of cigarettes smoked (factory-made or roll-your-own cigarettes), the brand of choice, the factors for choosing a specific brand and the degree of loyalty to that brand (not at all, a little, somewhat and a lot) were assessed by country, sociodemographics and smoking-related variables. RESULTS In total, 86.6% of the smokers reported having a usual brand. In three out of the six countries, one brand holds the loyalty of between 17.8% and 24.5% of the smokers that reported having a usual brand for factory-made cigarettes. Most participants reported being loyal 'a lot' to their brand of choice (44.4%). The reasons most reported for choosing a cigarette brand were the taste (83.2%) and the price (51.7%). CONCLUSIONS Brand loyalty is high among factory-made and roll-your-own cigarette smokers in six European countries. Future research on longitudinal trends of brand loyalty to evaluate the effect of tobacco control policies in these European countries is warranted

Knowledge of the health risks of smoking and impact of cigarette warning labels among tobacco users in six European countries: Findings from the EUREST-PLUS ITC Europe Surveys

INTRODUCTION The aim of this study was to examine knowledge of health effects of smoking and the impact of cigarette package warnings among tobacco users from six European Union (EU) Member States (MS) immediately prior to the introduction of the EU Tobacco Products Directive (TPD) in 2016 and to explore the interrelationship between these two factors. METHODS Cross-sectional data were collected via face-to-face interviews with adult smokers (n=6011) from six EU MS (Germany, Greece, Hungary, Poland, Romania, Spain) between June-September 2016. Sociodemographic variables and knowledge of health risks of smoking (KHR) were assessed. Warning salience, thoughts of harm, thoughts of quitting and foregoing of cigarettes as a result of health warnings were assessed. The Label Impact Index (LII) was used as a composite measure of warning effects. Linear and logistic regression analyses were used to examine sociodemographic predictors of KHR and LII and the inter-relationship between knowledge and LII scores. RESULTS The KHR index was highest in Romania and Greece and lowest in Hungary and Germany. While the majority of smokers knew that smoking increases the risk for heart diseases, lung and throat cancer, there was lower awareness that tobacco use caused mouth cancer, pulmonary diseases, stroke, and there were very low levels of knowledge that it was also associated with impotence and blindness, in all six countries. Knowledge regarding the health risks of passive smoking was moderate in most countries. The LII was highest in Romania and Poland, followed by Spain and Greece, and lowest in Germany and Hungary. In almost all countries, there was a positive association between LII scores and higher KHR scores after controlling for sociodemographic variables. Several sociodemographic factors were associated with KHR and LII, with differences in these associations documented across countries. CONCLUSIONS These data provide evidence to support the need for stronger educational efforts and policies that can enhance the effectiveness of health warnings in communicating health risks and promoting quit attempts. Data will serve as a baseline for examining the impact of the TPD

r84, a Novel Therapeutic Antibody against Mouse and Human VEGF with Potent Anti-Tumor Activity and Limited Toxicity Induction

Vascular endothelial growth factor (VEGF) is critical for physiological and pathological angiogenesis. Within the tumor microenvironment, VEGF functions as an endothelial cell survival factor, permeability factor, mitogen, and chemotactic agent. The majority of these functions are mediated by VEGF-induced activation of VEGF receptor 2 (VEGFR2), a high affinity receptor tyrosine kinase expressed by endothelial cells and other cell types in the tumor microenvironment. VEGF can also ligate other cell surface receptors including VEGFR1 and neuropilin-1 and -2. However, the importance of VEGF-induced activation of these receptors in tumorigenesis is still unclear. We report the development and characterization of r84, a fully human monoclonal antibody that binds human and mouse VEGF and selectively blocks VEGF from interacting with VEGFR2 but does not interfere with VEGF∶VEGFR1 interaction. Selective blockade of VEGF binding to VEGFR2 by r84 is shown through ELISA, receptor binding assays, receptor activation assays, and cell-based functional assays. Furthermore, we show that r84 has potent anti-tumor activity and does not alter tissue histology or blood and urine chemistry after chronic high dose therapy in mice. In addition, chronic r84 therapy does not induce elevated blood pressure levels in some models. The ability of r84 to specifically block VEGF∶VEGFR2 binding provides a valuable tool for the characterization of VEGF receptor pathway activation during tumor progression and highlights the utility and safety of selective blockade of VEGF-induced VEGFR2 signaling in tumors

Identification of novel targets for breast cancer by exploring gene switches on a genome scale

<p>Abstract</p> <p>Background</p> <p>An important feature that emerges from analyzing gene regulatory networks is the "switch-like behavior" or "bistability", a dynamic feature of a particular gene to preferentially toggle between two steady-states. The state of gene switches plays pivotal roles in cell fate decision, but identifying switches has been difficult. Therefore a challenge confronting the field is to be able to systematically identify gene switches.</p> <p>Results</p> <p>We propose a top-down mining approach to exploring gene switches on a genome-scale level. Theoretical analysis, proof-of-concept examples, and experimental studies demonstrate the ability of our mining approach to identify bistable genes by sampling across a variety of different conditions. Applying the approach to human breast cancer data identified genes that show bimodality within the cancer samples, such as estrogen receptor (ER) and ERBB2, as well as genes that show bimodality between cancer and non-cancer samples, where tumor-associated calcium signal transducer 2 (TACSTD2) is uncovered. We further suggest a likely transcription factor that regulates TACSTD2.</p> <p>Conclusions</p> <p>Our mining approach demonstrates that one can capitalize on genome-wide expression profiling to capture dynamic properties of a complex network. To the best of our knowledge, this is the first attempt in applying mining approaches to explore gene switches on a genome-scale, and the identification of TACSTD2 demonstrates that single cell-level bistability can be predicted from microarray data. Experimental confirmation of the computational results suggest TACSTD2 could be a potential biomarker and attractive candidate for drug therapy against both ER+ and ER- subtypes of breast cancer, including the triple negative subtype.</p