Personalised profiling to identify clinically relevant changes in tremor due to multiple sclerosis

Background: There is growing interest in sensor-based assessment of upper limb tremor in multiple sclerosis and other movement disorders. However, previously such assessments have not been found to offer any improvement over conventional clinical observation in identifying clinically relevant changes in an individual's tremor symptoms, due to poor test-retest repeatability. Method: We hypothesised that this barrier could be overcome by constructing a tremor change metric that is customised to each individual's tremor characteristics, such that random variability can be distinguished from clinically relevant changes in symptoms. In a cohort of 24 people with tremor due to multiple sclerosis, the newly proposed metrics were compared against conventional clinical and sensor-based metrics. Each metric was evaluated based on Spearman rank correlation with two reference metrics extracted from the Fahn-Tolosa-Marin Tremor Rating Scale: a task-based measure of functional disability (FTMTRS B) and the subject's self-assessment of the impact of tremor on their activities of daily living (FTMTRS C). Results: Unlike the conventional sensor-based and clinical metrics, the newly proposed ’change in scale’ metrics presented statistically significant correlations with changes in self-assessed impact of tremor (max R2>0.5,p< 0.05 after correction for false discovery rate control). They also outperformed all other metrics in terms of correlations with changes in task-based functional performance (R2=0.25 vs. R2=0.15 for conventional clinical observation, both p< 0.05).Conclusions: The proposed metrics achieve an elusive goal of sensor-based tremor assessment: improving on conventional visual observation in terms of sensitivity to change. Further refinement and evaluation of the proposed techniques is required, but our core findings imply that the main barrier to translational impact for this application can be overcome. Sensor-based tremor assessments may improve personalised treatment selection and the efficiency of clinical trials for new treatments by enabling greater standardisation and sensitivity to clinically relevant changes in symptoms

Extent and correlates of self-reported exposure to tobacco advertising, promotion and sponsorship in smokers: Findings from the EUREST-PLUS ITC Europe Surveys

Introduction: Tobacco advertising, promotion and sponsorship (TAPS) are known to promote tobacco consumption and to discourage smoking cessation. Consequently, comprehensive TAPS bans are effective measures to reduce smoking. The objective of this study was to investigate to what extent smokers are exposed to TAPS in general, and in various media and localities, in different European countries. Methods: A cross-sectional analysis of national representative samples of adult smokers in 2016 from Germany, Greece, Hungary, Poland, Romania, and Spain (EUREST-PLUS Project, n=6011), as well as England (n=3503) and the Netherlands (n=1213) (ITC Europe Surveys) was conducted. Prevalence of self-reported TAPS exposure is reported by country, and socioeconomic correlates were investigated using logistic regression models. Results: Self-reported exposure to TAPS varied widely among the countries, from 15.4 % in Hungary to 69.2 % in the Netherlands. In most countries, tobacco advertising was most commonly seen at the point of sale, and rarely noticed in mass media. The multivariate analysis revealed some variation in exposure to TAPS by sociodemographic factors. Age showed the greatest consistency across countries with younger smokers (18–24 years) being more likely to notice TAPS than older smokers. Conclusions: TAPS exposure tended to be higher in countries with less restrictive regulation but was also reported in countries with more comprehensive bans, although at lower levels. The findings indicate the need for a comprehensive ban on TAPS to avoid a shift of marketing efforts to less regulated channels, and for stronger enforcement of existing bans

A pathogenic role for germline PTEN variants which accumulate into the nucleus.

The PTEN gene encodes a master regulator protein that exerts essential functions both in the cytoplasm and in the nucleus. PTEN is mutated in the germline of both patients with heterogeneous tumor syndromic diseases, categorized as PTEN hamartoma tumor syndrome (PHTS), and a group affected with autism spectrum disorders (ASD). Previous studies have unveiled the functional heterogeneity of PTEN variants found in both patient cohorts, making functional studies necessary to provide mechanistic insights related to their pathogenicity. Here, we have functionally characterized a PTEN missense variant [c.49C>G; p.(Gln17Glu); Q17E] associated to both PHTS and ASD patients. The PTEN Q17E variant displayed partially reduced PIP3-catalytic activity and normal stability in cells, as shown using S. cerevisiae and mammalian cell experimental models. Remarkably, PTEN Q17E accumulated in the nucleus, in a process involving the PTEN N-terminal nuclear localization sequence. The analysis of additional germline-associated PTEN N-terminal variants illustrated the existence of a PTEN N-terminal region whose targeting in disease causes PTEN nuclear accumulation, in parallel with defects in PIP3-catalytic activity in cells. Our findings highlight the frequent occurrence of PTEN gene mutations targeting PTEN N-terminus whose pathogenicity may be related, at least in part, with the retention of PTEN in the nucleus. This could be important for the implementation of precision therapies for patients with alterations in the PTEN pathway

Patterns of tobacco use, quit attempts, readiness to quit and self-efficacy among smokers with anxiety or depression: Findings among six countries of the EUREST-PLUS ITC Europe Surveys

Introduction: We compared smoking behaviors, past quit attempts, readiness to quit and beliefs about quitting among current cigarette smokers with probable anxiety or depression (PAD) to those without PAD, from six European Union (EU) Member States (MS). Methods: A nationally representative cross-sectional sample of 6011 adult cigarette smokers from six EU MS (Germany, Greece, Hungary, Poland, Romania, Spain) was randomly selected through a multistage cluster sampling design in 2016. Respondents were classified as having PAD based on self-reported current diagnosis or treatment for anxiety or depression, or a positive screen for major depression, according to a validated two-item instrument. Sociodemographic characteristics, patterns of tobacco use, past quitting, readiness to quit, self-efficacy and beliefs about quitting were assessed for patients with and without PAD. Logistic regression was used to examine predictors of PAD. All analyses were conducted using the complex samples package of SPSS. Results: Among smokers sampled, 21.0% (95% CI: 19.3–22.9) were identified as having PAD. Logistic regression analyses controlling for socioeconomic variables and cigarettes smoked per day found smokers with PAD were more likely to have made an attempt to quit smoking in the past (AOR=1.48; 95% CI: 1.25–1.74), made a quit attempt in the last 12 months (AOR=1.75; 95% CI: 1.45–2.11), and report lower self-efficacy with quitting (AOR=1.83; 95% CI: 1.44–2.32) compared to smokers without PAD. Additionally, it was found that individuals with PAD were more likely to report having received advice to quit from a doctor or health professional and having used quitline support as part of their last quit attempt. Conclusions: Smokers with PAD report a greater interest in quitting in the future and more frequent failed quit attempts than smokers without PAD; however, the high rates of untreated anxiety or depression, nicotine dependence, low confidence in the ability to quit, infrequent use of cessation methods, as well as socioeconomic factors may make quitting difficult

Smoking in public places in six European countries: Findings from the EUREST-PLUS ITC Europe Survey

Introduction: Surveillance of tobacco consumption in public places is an important measure to evaluate the impact of tobacco control interventions over time. The objective of this study was to estimate the prevalence of smoking as seen by smokers and their smoking behaviour in public places, in six European countries. Methods: We used baseline data of the International Tobacco Control Six European countries (ITC 6E) Survey, part of the EUREST-PLUS Project, conducted in 2016 in national representative samples of about 1000 adult smokers aged 18 years and older in Germany, Greece, Hungary, Poland, Romania and Spain. For each setting (workplaces, restaurants, bars/pubs and discos) participants were asked whether they had seen someone smoking during their last visit there and whether they too had smoked there. We report the overall and by-country weighted prevalence of seeing someone smoking and the smokers’ own smoking behaviour at each setting. We also assess the relationship between seeing someone smoking and smoking themselves at these settings. Results: The prevalence of smoking as seen by smokers was 18.8% at workplaces, with high variability among countries (from 4.7% in Hungary to 40.8% in Greece). Among smokers visiting leisure facilities in the last year, during their last visit 22.7% had seen someone smoking inside restaurants and 12.2% had smoked themselves there, while for bars/pubs the corresponding prevalences were 33.9% and 20.4%, and inside discos 44.8% and 34.8%. Conclusions: Smoking is still prevalent at leisure facilities, particularly at discos in Europe, with high variability among countries. More extensive awareness campaigns and stricter enforcement are needed to increase the compliance of smokefree regulations, especially in leisure facilities

Social norms towards smoking and electronic cigarettes among adult smokers in seven European Countries: Findings from the EUREST-PLUS ITC Europe Surveys

Introduction: This study explores whether current smokers’ social norms towards smoking and electronic cigarettes (e-cigarettes) vary across seven European countries alongside smoking and e-cigarette prevalence rates. At the time of surveying, England had the lowest current smoking prevalence and Greece the highest. Hungary, Romania and Spain had the lowest prevalence of any e-cigarette use and England the highest. // Methods: Respondents were adult (≥18 years) current smokers from the 2016 EUREST-PLUS ITC (Romania, Spain, Hungary, Poland, Greece, Germany) and ITC 4CV England Surveys (N=7779). Using logistic regression, associations between country and (a) smoking norms and (b) e-cigarette norms were assessed, adjusting for age, sex, income, education, smoking status, heaviness of smoking, and e-cigarette status. // Results: Compared with England, smoking norms were higher in all countries: reporting that at least three of five closest friends smoke (19% vs 65–84% [AOR=6.9–24.0; Hungary–Greece]), perceiving that people important to them approve of smoking (8% vs 14–57% [1.9–51.1; Spain–Hungary]), perceiving that the public approves of smoking (5% vs 6–37% [1.7–15.8; Spain–Hungary]), disagreeing that smokers are marginalised (9% vs 16–50% [2.3–12.3; Poland–Greece]) except in Hungary. Compared with England: reporting that at least one of five closest friends uses e-cigarettes was higher in Poland (28% vs 36% [2.7]) but lower in Spain and Romania (28% vs 6–14% [0.3–0.6]), perceiving that the public approves of e-cigarettes was higher in Poland, Hungary and Greece (32% vs 36–40% [1.5–1.6]) but lower in Spain and Romania in unadjusted analyses only (32% vs 24–26%), reporting seeing e-cigarette use in public at least some days was lower in all countries (81% vs 12–55% [0.1–0.4]; Spain–Greece). // Conclusions: Smokers from England had the least pro-smoking norms. Smokers from Spain had the least pro-e-cigarette norms. Friend smoking and disagreeing that smokers are marginalised broadly aligned with country-level current smoking rates. Seeing e-cigarette use in public broadly aligned with countrylevel any e-cigarette use. Generally, no other norms aligned with product prevalence

Secondhand exposure to e-cigarette aerosols among smokers: A cross-sectional study in six European countries of the EUREST-PLUS ITC Europe Surveys

Introduction: Electronic cigarette (e-cigarette) use has grown significantly in some European Union (EU) Member States (MS). A better understanding of the exposure to secondhand e-cigarette aerosols (SHA) is necessary to develop and implement comprehensive regulations on e-cigarette use in public places. This study aims to assess the observation of e-cigarette use in public places, the self-reported exposure to SHA, and the level of users’ comfort using e-cigarettes in the presence of others. Methods: This is a cross-sectional study of the Wave 1 International Tobacco Control 6 European Countries Survey recruiting adult smokers (n=6011) across six EU MS: Germany, Greece, Hungary, Poland, Romania, and Spain, within the EURESTPLUS Project. A descriptive analysis was conducted to estimate the prevalence (%) of observed e-cigarette use in different places, frequency of self-reported exposure to SHA, and level of comfort using e-cigarettes in the presence of others. Results: In all, 31.0% of smokers observed others using e-cigarette in public places, 19.7% in indoor places where smoking is banned, and 14.5% indoors at work. Almost 37% of smokers reported to be ever exposed to SHA, ranging from 17.7% in Spain to 63.3% in Greece. The higher prevalence of observed e-cigarette use and passive exposure to SHA was reported by smokers of younger age, of higher educational level and those being current or former e-cigarette users. Part (8.8%) of the smokers who were also e-cigarette users reported feeling uncomfortable using e-cigarettes in the presence of others. Conclusions: A third of smokers from six EU MS reported being exposed to SHA. Prevalence differences were observed among the countries. In the context of scarce evidence on long-term health effects of exposure to SHA, precautionary regulations protecting bystanders from involuntary exposure should be developed

Receiving support to quit smoking and quit attempts among smokers with and without smoking related diseases: Findings from the EUREST-PLUS ITC Europe Surveys

Introduction: Having a chronic disease either caused or worsened by tobacco smoking does not always translate into quitting smoking. Although smoking cessation is one of the most cost-effective medical interventions, it remains poorly implemented in healthcare settings. The aim was to examine whether smokers with chronic and respiratory diseases were more likely to receive support to quit smoking by a healthcare provider or make a quit attempt than smokers without these diseases. Methods: This population-based study included a sample of 6011 adult smokers in six European countries. The participants were interviewed face-to-face and asked questions on sociodemographic characteristics, current diagnoses for chronic diseases, healthcare visits in the last 12 months and, if so, whether they had received any support to quit smoking. Questions on smoking behavior included nicotine dependence, motivation to quit smoking and quit attempts in the last 12 months. The results are presented as weighted percentages with 95% confidence intervals (CI) and as adjusted odds ratios with 95% CI based on logistic regression analyses. Results: Smokers with chronic respiratory disease, those aged 55 years and older, as well as those with one or more chronic diseases were more likely to receive smoking cessation advice from a healthcare professional. Making a quit attempt in the last year was related to younger age, high educational level, higher motivation to quit, lower nicotine dependence and having received advice to quit from a healthcare professional but not with having chronic diseases. There were significant differences between countries with smokers in Romania consistently reporting more support to quit as well as quit attempts. Conclusions: Although smokers with respiratory disease did indeed receive smoking cessation support more often than smokers without disease, many smokers did not receive any advice or support to quit during a healthcare visit