Effects of influential points and sample size on the selection and replicability of multivariable fractional polynomial models.

BACKGROUND: The multivariable fractional polynomial (MFP) approach combines variable selection using backward elimination with a function selection procedure (FSP) for fractional polynomial (FP) functions. It is a relatively simple approach which can be easily understood without advanced training in statistical modeling. For continuous variables, a closed test procedure is used to decide between no effect, linear, FP1, or FP2 functions. Influential points (IPs) and small sample sizes can both have a strong impact on a selected function and MFP model. METHODS: We used simulated data with six continuous and four categorical predictors to illustrate approaches which can help to identify IPs with an influence on function selection and the MFP model. Approaches use leave-one or two-out and two related techniques for a multivariable assessment. In eight subsamples, we also investigated the effects of sample size and model replicability, the latter by using three non-overlapping subsamples with the same sample size. For better illustration, a structured profile was used to provide an overview of all analyses conducted. RESULTS: The results showed that one or more IPs can drive the functions and models selected. In addition, with a small sample size, MFP was not able to detect some non-linear functions and the selected model differed substantially from the true underlying model. However, when the sample size was relatively large and regression diagnostics were carefully conducted, MFP selected functions or models that were similar to the underlying true model. CONCLUSIONS: For smaller sample size, IPs and low power are important reasons that the MFP approach may not be able to identify underlying functional relationships for continuous variables and selected models might differ substantially from the true model. However, for larger sample sizes, a carefully conducted MFP analysis is often a suitable way to select a multivariable regression model which includes continuous variables. In such a case, MFP can be the preferred approach to derive a multivariable descriptive model.

Perceived Health and Capacity to Cope With Stress in Recent Ex-smokers: Impact of Vaping Versus Quitting All Nicotine.

INTRODUCTION: Little is known about the continued use of nicotine following smoking cessation on perceived well-being in comparison to complete cessation of nicotine use. AIMS AND METHODS: To explore aspects of perceived well-being and coping among recent ex-smokers as a function of vaping status. Ever-daily smokers in the International Tobacco Control 4 country smoking and vaping surveys in 2016 (w1 N = 883) and 2018 (w2 N = 1088). Cross-sectional associations and longitudinal samples for those who quit between waves and those who quit at w1 and maintained abstinence to w2. Main outcome measures were: Past 30 days of depression symptoms, perceived stress, stress management since quitting, and change in perceived day-to-day health. RESULTS: In the cross-sectional analyses vapers were more likely to report both improved stress management (aOR = 1.71, 95% CI 1.23-2.36) and perceived day-to-day health (aOR = 1.65, 95% CI 1.26-2.16) than nicotine abstainers. In the longitudinal analyses, smokers who switched to vaping between waves (n = 372) were more likely to report depression symptoms at w2 (aOR = 2.00, 95% CI 1.09-3.65) but reported improved perceived health (aOR = 1.92, 95% CI 1.16-3.20). For the past daily smokers who remained quit between waves (n = 382), vapers were more likely to report improved stress management relative to abstainers (RRR = 5.05. 95% CI 1.19-21.40). There were no other significant differences between vapers and nicotine abstainers. CONCLUSIONS: There is little evidence to support the view that perceptions of well-being deteriorate in vapers compared to complete nicotine abstainers in the immediate years after smoking cessation. IMPLICATIONS: This study could find no conclusive evidence that the continued use of nicotine via e-cigarettes was detrimental to health compared to completely stopping nicotine intake altogether. Our results would suggest that continuing to use nicotine may even result in some benefits in the short term such as improved stress management, however further longitudinal studies are required to examine if these effects are restricted to the early post-quitting phase and whether other positive or negative effects on psychosocial health emerge in the future.

Inverse Probability Weighting Enhances Absolute Risk Estimation in Three Common Study Designs of Nosocomial Infections.

Purpose: When studying nosocomial infections, resource-efficient sampling designs such as nested case-control, case-cohort, and point prevalence studies are preferred. However, standard analyses of these study designs can introduce selection bias, especially when interested in absolute rates and risks. Moreover, nosocomial infection studies are often subject to competing risks. We aim to demonstrate in this tutorial how to address these challenges for all three study designs using simple weighting techniques. Patients and Methods: We discuss the study designs and explain how inverse probability weights (IPW) are applied to obtain unbiased hazard ratios (HR), odds ratios and cumulative incidences. We illustrate these methods in a multi-state framework using a dataset from a nosocomial infections study (n = 2286) in Moscow, Russia. Results: Including IPW in the analysis corrects the unweighted naïve analyses and enables the estimation of absolute risks. Resulting estimates are close to the full cohort estimates using substantially smaller numbers of patients. Conclusion: IPW is a powerful tool to account for the unequal selection of controls in case-cohort, nested case-control and point prevalence studies. Findings can be generalized to the full population and absolute risks can be estimated. When applied to a multi-state model, competing risks are also taken into account.

Structured reporting to improve transparency of analyses in prognostic marker studies.

BACKGROUND: Factors contributing to the lack of understanding of research studies include poor reporting practices, such as selective reporting of statistically significant findings or insufficient methodological details. Systematic reviews have shown that prognostic factor studies continue to be poorly reported, even for important aspects, such as the effective sample size. The REMARK reporting guidelines support researchers in reporting key aspects of tumor marker prognostic studies. The REMARK profile was proposed to augment these guidelines to aid in structured reporting with an emphasis on including all aspects of analyses conducted. METHODS: A systematic search of prognostic factor studies was conducted, and fifteen studies published in 2015 were selected, three from each of five oncology journals. A paper was eligible for selection if it included survival outcomes and multivariable models were used in the statistical analyses. For each study, we summarized the key information in a REMARK profile consisting of details about the patient population with available variables and follow-up data, and a list of all analyses conducted. RESULTS: Structured profiles allow an easy assessment if reporting of a study only has weaknesses or if it is poor because many relevant details are missing. Studies had incomplete reporting of exclusion of patients, missing information about the number of events, or lacked details about statistical analyses, e.g., subgroup analyses in small populations without any information about the number of events. Profiles exhibit severe weaknesses in the reporting of more than 50% of the studies. The quality of analyses was not assessed, but some profiles exhibit several deficits at a glance. CONCLUSIONS: A substantial part of prognostic factor studies is poorly reported and analyzed, with severe consequences for related systematic reviews and meta-analyses. We consider inadequate reporting of single studies as one of the most important reasons that the clinical relevance of most markers is still unclear after years of research and dozens of publications. We conclude that structured reporting is an important step to improve the quality of prognostic marker research and discuss its role in the context of selective reporting, meta-analysis, study registration, predefined statistical analysis plans, and improvement of marker research.

Reducing burden from respiratory infections in refugees and immigrants: a systematic review of interventions in OECD, EU, EEA and EU-applicant countries.

BACKGROUND: Respiratory diseases are a major reason for refugees and other immigrants seeking health care in countries of arrival. The burden of respiratory diseases in refugees is exacerbated by sometimes poor living conditions characterised by crowding in mass accommodations and basic living portals. The lack of synthesised evidence and guideline-relevant information to reduce morbidity and mortality from respiratory infections endangers this population. METHODS: A systematic review of all controlled and observational studies assessing interventions targeting the treatment, diagnosis and management of respiratory infections in refugees and immigrants in OECD, EU, EEA and EU-applicant countries published between 2000 and 2019 in MEDLINE, CINAHL, PSYNDEX and the Web of Science. RESULTS: Nine of 5779 identified unique records met our eligibility criteria. Seven studies reported an increase in vaccine coverage from 2 to 52% after educational multilingual interventions for respiratory-related childhood diseases (4 studies) and for influenza (5 studies). There was limited evidence in one study that hand sanitiser reduced rates of upper respiratory infections and when provided together with face masks also the rates of influenza-like-illness in a hard to reach migrant neighbourhood. In outbreak situations of vaccine-preventable diseases, secondary cases and outbreak hazards were reduced by general vaccination strategies early after arrival but not by serological testing after exposure (1 study). We identified evidence gaps regarding interventions assessing housing standards, reducing burden of bacterial pneumonia and implementation of operational standards in refugee care and reception centres. CONCLUSIONS: Multilingual health literacy interventions should be considered to increase uptake of vaccinations in refugees and immigrants. Immediate vaccinations upon arrival at refugee housings may reduce secondary infections and outbreaks. Well-designed controlled studies on housing and operational standards in refugee and immigrant populations early after arrival as well as adequate ways to gain informed consent for early vaccinations in mass housings is required to inform guidelines.

Nicotine replacement treatment, e-cigarettes and an online behavioural intervention to reduce relapse in recent ex-smokers: a multinational four-arm RCT.

BACKGROUND: Relapse remains an unresolved issue in smoking cessation. Extended stop smoking medication use can help, but uptake is low and several behavioural relapse prevention interventions have been found to be ineffective. However, opportunistic 'emergency' use of fast-acting nicotine replacement treatment or electronic cigarettes may be more attractive and effective, and an online behavioural Structured Planning and Prompting Protocol has shown promise. The present trial aimed to evaluate the clinical effectiveness and cost-effectiveness of these two interventions. DESIGN: A randomised controlled trial. SETTING: English stop smoking services and Australian quitlines, Australian social media and St Vincent's Hospital Melbourne, Fitzroy, VIC. PARTICIPANTS: Ex-smokers abstinent for at least 4 weeks, with some participants in Australia also recruited from 1 week post quit date. The planned sample size was 1400, but the trial was curtailed when 235 participants were recruited. INTERVENTIONS: Participants were randomised in permuted blocks of random sizes to (1) oral nicotine replacement treatment/electronic cigarettes to use if at risk of relapse, plus static text messages (n = 60), (2) the Structured Planning and Prompting Protocol and interactive text messages (n = 57), (3) oral nicotine replacement treatment/electronic cigarettes plus the Structured Planning and Prompting Protocol with interactive text messages (n = 58) or (4) usual care plus static text messages (n = 59). OUTCOME MEASURES: Owing to delays in study set-up and recruitment issues, the study was curtailed and the primary outcome was revised. The original objective was to determine whether or not the two interventions, together or separately, reduced relapse rates at 12 months compared with usual care. The revised primary objective was to determine whether or not number of interventions received (i.e. none, one or two) affects relapse rate at 6 months (not biochemically validated because of study curtailment). Relapse was defined as smoking on at least 7 consecutive days, or any smoking in the last month at final follow-up for both the original and curtailed outcomes. Participants with missing outcome data were included as smokers. Secondary outcomes included sustained abstinence (i.e. no more than five cigarettes smoked over the 6 months), nicotine product preferences (e.g. electronic cigarettes or nicotine replacement treatment) and Structured Planning and Prompting Protocol coping strategies used. Two substudies assessed reactions to interventions quantitatively and qualitatively. The trial statistician remained blinded until analysis was complete. RESULTS: The 6-month relapse rates were 60.0%, 43.5% and 49.2% in the usual-care arm, one-intervention arm and the two-intervention arm, respectively (p = 0.11). Sustained abstinence rates were 41.7%, 54.8% and 50.9%, respectively (p = 0.17). Electronic cigarettes were chosen more frequently than nicotine replacement treatment in Australia (71.1% vs. 29.0%; p = 0.001), but not in England (54.0% vs. 46.0%; p = 0.57). Of participants allocated to nicotine products, 23.1% were using them daily at 6 months. The online intervention received positive ratings from 63% of participants at 6 months, but the majority of participants (72%) completed one assessment only. Coping strategies taught in the Structured Planning and Prompting Protocol were used with similar frequency in all study arms, suggesting that these are strategies people had already acquired. Only one participant used the interactive texting, and interactive and static messages received virtually identical ratings. LIMITATIONS: The inability to recruit sufficient participants resulted in a lack of power to detect clinically relevant differences. Self-reported abstinence was not biochemically validated in the curtailed trial, and the ecological momentary assessment substudy was perceived by some as an intervention. CONCLUSIONS: Recruiting recent ex-smokers into an interventional study proved problematic. Both interventions were well received and safe. Combining the interventions did not surpass the effects of each intervention alone. There was a trend in favour of single interventions reducing relapse, but it did not reach significance and there are reasons to interpret the trend with caution. FUTURE WORK: Further studies of both interventions are warranted, using simpler study designs. TRIAL REGISTRATION: Current Controlled Trials ISRCTN11111428. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 68. See the NIHR Journals Library website for further project information. Funding was also provided by the National Health and Medical Research Council, Canberra, ACT, Australia (NHMRC APP1095880). Public Health England provided the funds to purchase the nicotine products in England.

Stop smoking services help people to stop smoking over a short period of time. However, nearly three-quarters of quitters return to smoking (i.e. relapse) within 1 year. Effective relapse prevention strategies are needed. Traditional behavioural relapse prevention strategies (e.g. teaching techniques to resist having a cigarette) have not proved effective. However, an earlier study showed that an online programme guiding smokers in stopping smoking and remaining abstinent reduced relapse between 1 week and 6 months. Long-term use of stop smoking medications (e.g. nicotine replacement treatment) can also help, but most successful quitters do not continue to use them. Nicotine mouth spray, lozenges or electronic cigarettes that can quickly help relieve urges to smoke and that ex-smokers can use 'in emergencies' could be a more attractive option. We planned to test these two interventions, on their own and together, in 1400 participants who had quit ≥ 4 weeks previously and who were recruited from English stop smoking services and Australian quitlines. We would then compare these participants with the participants following usual care (i.e. access to stop smoking medications used during the quit attempt for up to 3 months). Owing to delays in study set-up and difficulties in recruiting, the study recruited only 234 participants (n = 131 in Australia and n = 103 in England). We studied participants' reactions to the two interventions and to their combination, and how clinically effective the interventions were. Both interventions were rated positively by most participants. Among the participants in Australia, electronic cigarettes were more popular than medical nicotine products. In England, both products were equally popular. Participants in the online intervention group appreciated the advice on coping strategies, but they rarely completed repeat assessments. In addition, participants who were not in this group used the strategies just as much. There were hints that the interventions may be helpful in preventing relapse. There is an indication that the two interventions combined did not do any better than each on its own, but this requires replication in a larger study. Although the interventions show promise, the small number of participants recruited means that we are unable to make strong conclusions. The study identified areas for future work.

Evaluating the impact of introducing standardized packaging with larger health-warning labels in England: findings from adult smokers within the EUREST-PLUS ITC Europe Surveys.

BACKGROUND: The European (EU) Tobacco Product Directive (TPD) was implemented in May 2016 to regulate the design and labelling of cigarettes and roll-your-own tobacco. At the same time, the UK introduced standardized packaging measures, whereas Germany, Greece, Hungary, Poland, Romania and Spain did not. This study examines the impact of introducing standardized packaging in England using a quasi-experimental design. METHODS: Data from adult smokers in Waves 1 (2016; N=9547) and 2 (2018; N=9724) from the International Tobacco Control Policy Evaluation surveys (England) and EUREST-PLUS surveys (Germany, Greece, Hungary, Poland, Romania and Spain) were used. Generalized estimating equations were used to estimate changes in pack/brand appeal, salience of health-warning labels (HWLs) and perceived relative harm of different brands in England (where larger HWLs and standardized packaging were implemented), vs. each EU country (where only larger HWLs were implemented). RESULTS: There was an increase in the percentage of respondents from Germany, Hungary and Poland reporting they did not like the look of the pack (4.7%, 9.6%, and 14.2%, respectively), but the largest increase was in England (41.0%). Moreover, there was a statistically significant increase in the salience of HWLs in Hungary, Poland and Romania (17.0%, 13.9%, and 15.3%, respectively), but the largest increase was in England (27.6%). Few differences were observed in cross-country comparisons of the perceived relative harm of different brands. CONCLUSIONS: Findings suggest that standardized packaging reduces pack appeal and enhances the salience of HWLs over and above the effects of larger HWLs. Findings provide additional evidence and support for incorporating standardized packaging into the EU TPD.

Awareness and correlates of noticing changes to cigarette packaging design after implementation of the European Tobacco Products Directive: findings from the EUREST-PLUS ITC Europe Surveys.

BACKGROUND: The European Tobacco Products Directive (TPD), which went into effect in May 2016, regulates packaging design and labelling of cigarettes and roll-your-own (RYO) tobacco. The aim of the current study was to examine whether smokers and recent quitters in six European Union (EU) countries (Germany, Greece, Hungary, Poland, Romania and Spain) reported noticing TPD-related changes to packaging, and correlates of noticing these changes. METHODS: Cross-sectional data from the Wave 2 of the ITC 6 European Country Survey in 2018 after implementation of the TPD. Bivariate analyses included adult smokers (n = 5597) and recent quitters (n = 412). Adjusted logistic regression analyses were restricted to the subset of current smokers (n = 5597) and conducted using SAS-callable SUDAAN. RESULTS: Over half of smokers (58.2%) and 30% of quitters noticed at least one of five types of TPD-related pack changes. Over one-quarter of all respondents noticed changes to health warnings (30.0%), standardized openings (27.7%), minimum pack unit size (27.9%), and the removal of tar, nicotine and carbon monoxide information (26.7%) on packaging. Cross-country differences were observed across all measures, with noticing all pack changes markedly lower in Spain than the other countries. Correlates of noticing specific pack changes included sociodemographic characteristics, smoking behaviours and related to packaging. CONCLUSIONS: This is one of the first cross-country studies to examine the extent to which TPD changes to cigarette and RYO tobacco packaging are being noticed by smokers and recent quitters. Findings indicate that the majority of smokers noticed at least one type of pack change, but this varied across countries and sub-populations.

Impact of the Tobacco Products Directive on self-reported exposure to e-cigarette advertising, promotion and sponsorship in smokers-findings from the EUREST-PLUS ITC Europe Surveys.

BACKGROUND: Advertising, promotion and sponsorship of electronic cigarettes (ECAPS) have increased in recent years. Since May 2016, the Tobacco Products Directive 2014/40/EU (TPD2) prohibits ECAPS in various advertising channels, including media that have cross-border effects. The objective of this study was to investigate changes in exposure to ECAPS in a cohort of smokers from six European Union member states after implementation of TPD2. METHODS: Self-reported exposure to ECAPS overall and in various media and localities was examined over two International Tobacco Control Policy Evaluation survey waves (2016 and 2018) in a cohort of 6011 adult smokers from Germany, Greece, Hungary, Poland, Romania and Spain (EUREST-PLUS Project) using longitudinal generalized estimating equations models. RESULTS: Self-reported ECAPS exposure at both timepoints varied between countries and across examined advertising channels. Overall, there was a significant increase in ECAPS exposure [adjusted odds ratio (aOR): 1.25, 95% CI: 1.09-1.44]. Between waves, no consistent patterns of change in ECAPS exposure across countries and different media were observed. Generally, ECAPS exposure tended to decline in some channels regulated by TPD2, particularly on television and radio, while exposure tended to increase in some unregulated channels, such as at points of sale. CONCLUSIONS: The findings suggest that the TPD2 was generally effective in reducing ECAPS in regulated channels. Nonetheless, further research is warranted to evaluate its role in reducing ECAPS exposure, possibly by triangulation with additional sources of data.

Effectiveness of tobacco warning labels before and after implementation of the European Tobacco Products Directive-findings from the longitudinal EUREST-PLUS ITC Europe surveys.

BACKGROUND: Tobacco product packaging is a key part of marketing efforts to make tobacco use appealing. In contrast, large, prominent health warnings are intended to inform individuals about the risks of smoking. In the European Union, since May 2016, the Tobacco Products Directive 2014/40/EU (TPD2) requires tobacco product packages to carry combined health warnings consisting of a picture, a text warning and information on stop smoking services, covering 65% of the front and back of the packages. METHODS: Key measures of warning label effectiveness (salience, cognitive reactions and behavioural reaction) before and after implementation of the TPD2, determinants of warning labels' effectiveness and country differences were examined in a longitudinal sample of 6011 adult smokers from Germany, Greece, Hungary, Poland, Romania and Spain (EUREST-PLUS Project) using longitudinal Generalized Estimating Equations (GEE) models. RESULTS: In the pooled sample, the warning labels' effectiveness increased significantly over time in terms of salience (adjusted OR = 1.18; 95% CI: 1.03-1.35), while cognitive and behavioural reactions did not show clear increases. Generally, among women, more highly educated smokers and less addicted smokers, the effectiveness of warning labels tended to be higher. CONCLUSION: We found an increase in salience, but no clear increases for cognitive and behavioural reactions to the new warning labels as required by the TPD2. While it is likely that our study underestimated the impact of the new pictorial warning labels, it provides evidence that health messages on tobacco packaging are more salient when supported by large pictures.

Quitting behaviours and cessation methods used in eight European Countries in 2018: findings from the EUREST-PLUS ITC Europe Surveys.

BACKGROUND: We examined quit attempts, use of cessation assistance, quitting beliefs and intentions among smokers who participated in the 2018 International Tobacco Control (ITC) Europe Surveys in eight European Union Member States (England, Germany, Greece, Hungary, the Netherlands, Poland, Romania and Spain). METHODS: Cross-sectional data from 11 543 smokers were collected from Wave 2 of the ITC Six European Country (6E) Survey (Germany, Greece, Hungary, Poland, Romania and Spain-2018), the ITC Netherlands Survey (the Netherlands-late 2017) and the Four Countries Smoking and Vaping (4CV1) Survey (England-2018). Logistic regression was used to examine associations between smokers' characteristics and recent quit attempts. RESULTS: Quit attempts in the past 12 months were more frequently reported by respondents in the Netherlands (33.0%) and England (29.3%) and least frequently in Hungary (11.5%), Greece (14.7%), Poland (16.7%) and Germany (16.7%). With the exception of England (35.9%), the majority (56-84%) of recent quit attempts was unaided. Making a quit attempt was associated with younger age, higher education and income, having a smoking-related illness and living in England. In all countries, the majority of continuing smokers did not intend to quit in the next 6 months, had moderate to high levels of nicotine dependence and perceived quitting to be difficult. CONCLUSIONS: Apart from England and the Netherlands, smokers made few quit attempts in the past year and had low intentions to quit in the near future. The use of cessation assistance was sub-optimal. There is a need to examine approaches to supporting quitting among the significant proportion of tobacco users in Europe and increase the use of cessation support as part of quit attempts.

Annotation of Human Exome Gene Variants with Consensus Pathogenicity.

A novel approach is developed to address the challenge of annotating with phenotypic effects those exome variants for which relevant empirical data are lacking or minimal. The predictive annotation method is implemented as a stacked ensemble of supervised base-learners, including distributed random forest and gradient boosting machines. Ensemble models were trained and cross-validated on evidence-based categorical variant effect annotations from the ClinVar database, and were applied to 84 million non-synonymous single nucleotide variants (SNVs). The consensus model combined 39 functional mutation impacts, cross-species conservation score, and gene indispensability score. The indispensability score, accounting for differences in variant pathogenicities including in essential and mutation-tolerant genes, considerably improved the predictions. The consensus combination is consistent with as many input scores as possible while minimizing false predictions. The input scores are ranked based on their ability to predict effects. The score rankings and categorical phenotypic variant effect predictions are aimed for direct use in clinical and biological applications to prioritize human exome variants and mutations.

A multi-state model analysis of the time from ethical approval to publication of clinical research studies.

BACKGROUND: Results of medical research should be made publicly available in a timely manner to enable patients and health professionals to make informed decisions about health issues. We aimed to apply a multi-state model to analyze the overall time needed to publish study results, and to examine predictors of the timing of transitions within the research process from study initiation through completion/discontinuation to eventual publication. METHODS: Using a newly developed multi-state model approach, we analysed the effect of different study-related factors on each of the transitions from study approval to eventual publication, using a data set of clinical studies approved by a German research ethics committee between 2000 and 2002. RESULTS: Of 917 approved studies, 806 were included in our analyses. About half of the clinical studies which began were subsequently published as full articles, and the median time from study approval to publication was 10 years. Differences across model states were apparent; several factors were predictive of the transition from study approval to completion, while funding source and collaboration were predictive of the transition from completion to publication. CONCLUSIONS: The proposed multi-state model approach permits a more comprehensive analysis of time to publication than a simple examination of the transition from approval to publication, and thus the findings represent an advance on previous studies of this aspect of the research process.

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.

A multi-state model based reanalysis of the Framingham Heart Study: Is dementia incidence really declining?

Recent research by Satizabal and colleagues using data from the Framingham Heart Study demonstrated a linear decline in dementia incidence since the 1970s. The aim of this study is to re-examine these findings, given concerns that bias resulted from failure to account for the probability of acquiring dementia between the last dementia-free observation and death. This analysis included 5118 persons 60+ years of age, and determined the 5-year dementia incidence during four non-overlapping epochs. In addition to a replication using Cox proportional hazards, we applied separate Cox models (given unequal hazards across epochs) and a Spline-based penalized likelihood approach based on the illness-death multi-state model. In addition, we present a simulation study demonstrating the bias associated with the use of standard survival models. The simulation showed that estimates of disease incidence derived from the multi-state model-based approach were consistent with the true disease incidence, whereas Cox regression 'censoring' observations at death or at last observation consistently underestimated it. Using the Framingham data, the 5-year age- and sex-adjusted cumulative hazard rates for dementia as derived from the multi-state model-based approach were 3.84, 2.66, 3.29 and 3.13 per 100 persons in epochs 1, 2, 3 and 4 respectively. The findings do not support the conclusion that dementia incidence has declined in the Framingham Heart Study over the given time period. Previous findings of a decline may have been an artefact resulting from improper treatment of those cases in which death precluded the observation of dementia onset.

Cohort studies were found to be frequently biased by missing disease information due to death.

OBJECTIVES: In epidemiologic cohort studies with missing disease information due to death (MDID), conventional analyses right-censoring death cases at the last observation or at death may yield significant bias in relative risk and hazard ratio estimates. The aim of this study was to investigate susceptibility to this bias and assess its potential direction and magnitude. STUDY DESIGN AND SETTING: Literature review of selected epidemiologic, geriatric, and environmental journals in 2011-2012 and simulation study of various conventional approaches to handling missing disease data. A study was considered susceptible to MDID bias if disease information was collected at follow-up visits only, and a conventional analysis was performed on the data. RESULTS: Of 125 identified studies, 58 (46.4%, 95% confidence interval [CI]: 37.7-55.1%) were classified as susceptible to MDID bias, of which six (10.3%, 95% CI: 2.5-18.2%) attempted to address this in sensitivity analyses. The simulation revealed that depending on the analytic strategy for handling missing disease data, the potential exists for significant under- or over-estimation of risk factor effect estimates. CONCLUSION: Awareness of MDID bias is important as more adequate analysis methods exist permitting an unbiased analysis. Recommendations for better reporting and analysis of MDID are provided.

The association between the nature of the goal committed to and quitting smoking.

Commitments to goals are theorized to affect behavior change outcomes, but competing theories argue for hard to achieve goals and strategic sub-goals as optimum strategies for success. This study aimed to explore whether the nature of the goal affects smoking cessation outcomes. A total of 1043 participants in a randomized controlled trial of variations to an automated computer generated cessation advice program, who had made a quit attempt were asked at 1 month post quit about the initial goal they had set at the time of making the attempt. They were also followed up at 6 months post quit. Compared with those reporting 'seeing how it will go', those who reported the goal of 'taking it a cigarette at a time' were less likely to be quit at 1 month, while those with the most ambitious goal, to 'never smoke again', were more likely to be quit, and were more likely to maintain abstinence for 6 months. Indeed, 'taking it a cigarette at a time' was associated with greater short-term relapse. There is likely to be a benefit in encouraging smokers to set ambitious long-term goals rather than setting intermediate or non-specific goals.

Smokers' perceptions of sources of advice about quitting: findings from the Australian arm of the ITC 4-country survey.

Smokers are exposed to advice about quitting from numerous sources. Within the 2013 ITC 4-Country Survey, 1211 Australian smokers or recent ex-smokers rated the perceived importance of eight sources of advice, categorized into evidence-based, non evidence-based, personal experience and vicarious experience (two items each), and also rated their intention to quit, nicotine dependence, use of quit medication, health concerns and harm beliefs. The eight items were all positively correlated. Respondents who placed greater importance on their experiences (either personal or vicarious) were more likely to agree that the evidence for smoking-related harm is exaggerated, and although not more likely to intend to quit overall, these responses were most strongly related to quit intention. Notably, of those responding that all sources were 'not at all important' (or don't know), only 3.2% reported any interest in quitting in the next 6 months (compared to 36.0% among those who endorsed any), 12.8% were often concerned about smoking's effect on their health (compared with 60.4%), and 73.7% agreed that 'smoking is no more risky than other things' (compared with 34.5%). There was no evidence that rejecting evidence-based sources (medical or governmental) in favour of other sources was associated with lower quit intentions or behaviour.

Prevalence and Correlates of the Belief That Electronic Cigarettes are a Lot Less Harmful Than Conventional Cigarettes Under the Different Regulatory Environments of Australia and the United Kingdom.

INTRODUCTION: The rapid rise in electronic cigarettes (ECs) globally has stimulated much debate about the relative risk and public health impact of this new emerging product category as compared to conventional cigarettes. The sale and marketing of ECs containing nicotine are banned in many countries (eg, Australia) but are allowed in others (eg, United Kingdom). This study examined prevalence and correlates of the belief that ECs are a lot less harmful than conventional cigarettes under the different regulatory environments in Australia (ie, more restrictive) and the United Kingdom (ie, less restrictive). METHODS: Australian and UK data from the 2013 survey of the International Tobacco Control Four-Country project were analyzed. RESULTS: More UK than Australian respondents (58.5% vs. 35.2%) believed that ECs are a lot less harmful than conventional cigarettes but more respondents in Australia than in the United Kingdom selected "Don't Know" (36.5% vs. 17.1%). The proportion that responded "A little less, equally or more harmful" did not differ between countries. Correlates of the belief that ECs are "A lot less harmful" differed between countries, while correlates of "Don't Know" response did not differ. CONCLUSIONS: Consistent with the less restrictive regulatory environment affecting the sale and marketing of ECs, smokers and recent ex-smokers in the United Kingdom were more likely to believe ECs were less harmful relative to conventional cigarettes compared to those in Australia. IMPLICATIONS: What this study adds: Among smokers and ex-smokers, this study found that the belief that ECs are (a lot) less harmful than conventional cigarettes was considerably higher in the United Kingdom than in Australia in 2013. The finding is consistent with the less restrictive regulatory environment for ECs in the United Kingdom, suggesting that the regulatory framework for ECs adopted by a country can affect smokers' perceptions about the relative harmfulness of ECs, the group that stands to gain the most from having an accurate belief about the relative harms of ECs.

Impact of the introduction of standardised packaging on smokers' brand awareness and identification in Australia.

INTRODUCTION AND AIMS: The introduction of standardised packaging (SP) in Australia in December 2012 has heightened interest in how image and branding might affect smoking. This paper tests the hypothesis that brand awareness and identification among smokers will decline after the introduction of SP. DESIGN AND METHODS: Longitudinal study of three waves of smokers in Australia, conducted between October 2011-February 2012 (pre-SP) (n = 1104), February-May 2013 (post-SP1) (n = 1093) and August-December 2014 (post-SP2) (n = 1090). We explored the extent of changes in two variables, brand awareness (noticing others with the brand of cigarettes you smoke) and brand identification (perceiving something in common among smokers of your brand), and examined change in a number of other measures of brand appeal, brand characteristics and determinants of brand choice. RESULTS: Brand awareness 'at least sometimes' reduced from 45.3% pre-SP to 26.9% at post-SP2 [odds ratio (OR) 0.35 (0.27-0.45)]. Brand identification also decreased from 18.2% to 12.7% [OR 0.62 (0.42-0.91)]. Significant decline was also found in measures of perceived brand prestige [OR 0.51 (0.39-0.66)] and choice of brand for health reasons [OR 0.45 (0.32-0.63)]. Liking the look of the pack was strongly associated with brand identification, but only post-SP (P = 0.02 for interaction across the three waves). DISCUSSION AND CONCLUSIONS: The introduction of SP of tobacco products in Australia has been associated with reductions in brand awareness and identification, and changes in related measures. The findings support the notion that SP has reduced the capacity for smokers to use pack branding to create and communicate a desired identity. [Balmford J, Borland R, Yong H-H. Impact of the introduction of standardised packaging on smokers' brand awareness and identification in Australia. Drug Alcohol Rev 2015;00:000-000].