Rationale and objectives: Alcohol and nicotine are the most commonly abused drugs and they are often taken together. To help address some of clinical issues regarding nicotine and alcohol co-dependence, a procedure in which rats self-administer nicotine intravenously and alcohol orally during the same operant session has been developed. Methods: Male Wistar rats were trained to self-administer alcohol (12%, w/v; 0.19 ml/delivery) or implanted with jugular catheters and trained to self-administer nicotine (30 μg/kg IV/infusion) by pressing a lever or were trained to self-administer both drugs, some with alcohol first, and others with nicotine first. Results: Animals readily coadministered alcohol and nicotine concurrently. Access to alcohol reduced nicotine selfadministration significantly. Conclusions: These results show that rats will self-administer relevant amounts of intravenous nicotine and oral alcohol concurrently. They also provide further support for the important relationship between nicotine and alcohol.

Rationale and objectives: Alcohol and nicotine are the most commonly abused drugs and they are often taken together. To help address some of clinical issues regarding nicotine and alcohol co-dependence, a procedure in which rats self-administer nicotine intravenously and alcohol orally during the same operant session has been developed. Methods: Male Wistar rats were trained to self-administer alcohol (12%, w/v; 0.19 ml/delivery) or implanted with jugular catheters and trained to self-administer nicotine (30 μg/kg IV/infusion) by pressing a lever or were trained to self-administer both drugs, some with alcohol first, and others with nicotine first. Results: Animals readily coadministered alcohol and nicotine concurrently. Access to alcohol reduced nicotine selfadministration significantly. Conclusions: These results show that rats will self-administer relevant amounts of intravenous nicotine and oral alcohol concurrently. They also provide further support for the important relationship between nicotine and alcohol.

In Canada, nicotine replacement therapy (NRT) is a best practice for adult smoking cessation, but it is not recommended for use by youth smokers. Previous research has indicated that more than 20 percent of high school-aged smokers in Canada had used NRT, despite the cross-Canada requirement that youths under the age of 18 have a physician’s prescription to purchase NRT. The goal of this study was to examine both student and school-level characteristics associated with use of NRT by youths. Data from 29,296 grade 9 to 12 students who participated in the 2008-2009 National Youth Smoking Survey (YSS) were combined with Canadian census and built environment data in multilevel logistic regression models. The associations between lifetime and current NRT use with student characteristics (i.e., smoking status, social smoking connections) were examined alongside school environment factors such as urban/rural location and pharmacy density within a one kilometre radius of schools. In 2008-2009, 21.1% of youth smokers in Canada had ever used NRT and 5.1% were currently using NRT. Odds of NRT use were highest among daily smokers, boys, youths who had made multiple quit attempts, and youths who self-identified as smokers. Attending a school located within an urban area increased youths’ odds of NRT use, whereas higher density of pharmacies surrounding a school was inversely associated with NRT use. This study is the first to identify significant between school differences in NRT use. It also reveals that many youths are using NRT in the absence of a quit attempt. Further research is needed to identify school characteristics that impact NRT use, and understand how youths are accessing NRT.

Background: Across North America, smoking prevalence is highest among young adults (YAs). Understanding the cessation behaviours of YAs is critical given their higher smoking rates; however, there is a paucity of prospective studies on YA cessation from a population-based sample of smokers. Objectives: This study characterizes younger and older adult smokers as well as identifies the rate of making a quit attempt (QA) and smoking cessation among a representative sample of younger and older adult smokers. Guided by the Social Cognitive Theory (SCT), this study also examines the interpersonal predictors of moving toward smoking cessation among YAs. Methods: Self-report data on 592 YA and 2777 older adult smokers were compiled from the Ontario Tobacco Survey baseline and six-month follow-up interviews. Smoking cessation behaviour was measured as an ordinal variable: made no attempt to quit, made a QA that lasted for less than 30 days, and successfully quit for 30 days or longer. Design-based analyses examined the characteristics of young and older adult smokers. Making a QA and smoking cessation during a six-month follow-up period were modeled according to the SCT constructs while accounting for the complex study design. Results: Young adult smokers were more likely to be men with lower levels of addiction but greater self-efficacy and an intention to quit than their older counterparts. While YA smokers were more likely to make a QA than their older counterparts (25% vs. 17%, respectively), they were no more likely to succeed (14% vs. 10%, respectively). Having an intention to quit smoking and having made two or more lifetime number of QAs predicted making a QA; the use of smoking cessation aids or resources and having knowledge that stop smoking medications make quitting a lot easier also contributed to making an attempt to quit. Self-efficacy, use of smoking cessation aids or resources and having someone to support one‘s QA were positive predictors of quitting whereas having high levels of addiction was a negative predictor of cessation. Conclusions: Young and older adults are distinct types of smokers with different personal and smoking characteristics. Different factors predicted making a QA and smoking cessation among YAs. Smoking cessation interventions for YAs should provide social support and skills to build and maintain self-efficacy to quit. It is critical to ensure YA smokers have effective smoking cessation aids and services that are easily accessible and appropriate for this population. Future research is needed to understand long-term smoking cessation and relapse in this vulnerable population.

Objective: The main objective was to examine characteristics associated with cigarette access behaviours among underage current youth smokers. Methods: This cross-sectional study used self-reported data collected from 29,296 students in Grades 9 to 12 who participated in the 2008-09 Youth Smoking Survey (YSS), and data from the 2008-09 DMTI-EPOI (Enhanced Points of Interest) data file. Multilevel logistic regression analyses were used to jointly examine whether student characteristics and the number of tobacco retailers surrounding schools were associated with the odds of a current youth smoker accessing cigarettes from: (a) a retailer source, (b) a family member, and (c) a friend or someone else. Results: Among underage current smokers, the majority reported usually buying their own cigarettes from a retailer (44.1%), and getting cigarettes from a friend or someone else (42.2%). Significant between-school random variation was identified for youth cigarette access from a retailer source, and from a friend or stranger. Males were more likely to buy their own cigarettes from a retailer (OR 2.08, 95% CI 1.74-2.48), whereas females were more likely to access cigarettes from a family member (OR 0.68, 95% CI 0.53-0.88), or a friend or someone else (OR 0.52, 95% CI 0.44-0.61). Binge smoking was associated with buying cigarettes from a retailer (OR 0.65, 95% CI 0.48-0.86). Youth with a smoking parent or guardian (OR 2.95, 95% CI 2.02-4.31) were more likely to get cigarettes from a family member. Youth who reported that they sometimes (OR 2.80, 95% CI 1.94-4.04), or usually or always (OR 3.15, 95% CI 2.17-4.58) share cigarettes with others was associated with accessing cigarettes from a friend or someone else. Each additional tobacco retailer surrounding a school was associated with an increased likelihood of youth purchasing their own cigarettes from a retailer (OR 1.04, 95% CI 1.01-1.07). Conclusion: Tobacco point-of-sale restrictions are inadequate as youth can still procure cigarettes from both retailers and social sources. Future studies should explore beyond individual-level factors and examine what influences cigarette access behaviours in the broader school context. Such insight will inform the development of new school-level tobacco control initiatives that can more effectively prevent youth from acquiring cigarettes.

As shisha smoking is increasing globally, the need for a critical action to control shisha smoking consumption becomes crucial. Despite the success of cigarette warning labels in increasing smokers' awareness of the negative health effects of smoking and in motivating smokers to quit, nothing is known about the potential impact health warning labels may have on shisha users. The current study investigated the perception of effectiveness of text-only versus graphic warning among shisha smokers. This study sought to examine the impact of viewing health warning labels on perceived susceptibility and severity of shisha smoking health hazards, on motivating intentions to quit, and on changing the pattern of shisha smoking. Eligible participants first completed an online baseline questionnaire, and were then randomly assigned to one of three conditions:a control condition, in which they viewed nutrition labels (n=100) , or one of two experimental groups in which they viewed Text- only warning labels (n=117), or they viewed Graphic warning labels (n=125). In each of these three conditions, participants viewed six health warning labels and rated them using likert scale questions immediately following each label. Two weeks later, participants were invited to complete an online follow-up questionnaire. The findings indicate that Graphic tobacco warnings grab participants' attention and elicit unfavourable emotional reactions. Although there was a relatively little impact of viewing health warnings on subsequent shisha use, Graphic warnings significantly improved some of the participants' health knowledge .In addition, Graphic warnings significantly increased smokers' beliefs that shisha is harmful to health and dangerous to non-smokers. Patterns of the findings revealed that quit intentions were relatively higher among those who viewed Graphic warning labels. To our knowledge, this study is the first to examine the effect of health warnings on shisha smokers. Overall, findings provide modest support for the efficcacy of shisha warnings on establised users. Findings imply that packaging and labelling policies for shisha and shisha products require additional development. Further examination of specific themes and contents of health warnings directed specifically to shisha smokers in different cultural settings will be critical to ensure the relevance of health warnings in distinct cultural settings.

Most adult smokers begin smoking during adolescence; nicotine dependence can develop relatively quickly and, once established, most smokers smoke for approximately 40 years. For adolescents dependent upon nicotine, cessation interventions are not well established. It is, therefore, essential that public health interventions focus on preventing initiation and maintenance and decreasing the prevalence of youth smoking. In spite of legislation to protect New Zealand adolescents, a large proportion continues to use tobacco at least weekly. Recent surveys have shown a slight decrease in cigarette smoking prevalence, overall, but, no reduction and marked increases have been reported within some subgroups. The overall aim of this research was to identify school and personal factors associated with secondary school students smoking. The specific research objectives included: a) identifying factors at the personal, family, peer, school and 'tobacco-genic' environment levels which were associated with regular and established cigarette smoking; b) describing the extent of smoke-free policy and health education programmes in secondary schools; and, c) evaluating the relations between cigarette smoking among students and potential protective factors, smoke-free policies and practices and health education programmes. The research was based on data from 3,434 secondary school students from 82 schools. The multi-stage sampling procedures and data analyses ensured that the results were able to be generalised to the New Zealand secondary school student population. Smoking was more prevalent amongst girls for all measures of smoking frequency and significant differences were found for smoking prevalence between ethnic groups and school decile. In terms of family influences, the smoking behaviours of parents were not associated with increased odds of smoking nor were perceived relationships between students and their parents, or exposure to SHS. In contrast, the smoking behaviour of siblings was associated with increased odds of smoking but it is likely that both student and sibling smoking are both influenced by the same processes within the family. Similarly, low levels of self-concept were not associated with increased odds for daily smoking. The smoking behaviour of a best friend was a pervasive risk factor as was a high level of disposable income, frequent episodes of unsupervised activities, and 'pro-smoking' knowledge. Being male, visiting a place of worship, and the intention to stay at school until after Year 13 reduced the odds of daily smoking among students. Multilevel models were used to identify school level effects. After adjusting for student, family and school characteristics significant between-school variance in smoking prevalence remained and this suggests that there are factors, arguably beyond the immediate control of the student or family that may influence a student�s smoking behaviour. The presence of a school effect also supports the WHO concept of 'health promoting schools' in that schools can make a difference to health outcomes. Understanding how the health promoting schools model has been interpreted and implemented in NZ schools, along with critique of the implementation of the amended legislation making all schools smoke-free, would be a pertinent 'next-step' in identifying characteristics of schools which are associated with decreased tobacco use.

ABSTRACT Background Oesophageal cancer has a high mortality; it is the 6th most common cause of death due to cancer worldwide. Of the common subtypes of oesophageal cancer, it is the adenocarcinomas that have been rising rapidly in incidence throughout the western world. The incidence of adenocarcinomas now exceeds the previously common squamous cell carcinoma. These recent changes in the incidence patterns of oesophageal cancer suggests that the environmental risk factors associated with these subtypes differ, and that changes in the prevalence of these exposures over time are the most likely explanation for the observed shifts in the incidence. However, due to its low incidence until a few decades ago, the adenocarcinoma subtype has been less studied compared to squamous cell carcinoma, and the environmental factors associated with this cancer have not been so clearly defined. Smoking and alcohol have been the strongest environmental risk factors reported for oesophageal squamous cell carcinoma (OSCC) whereas for oesophageal adenocarcinoma (OAC), the effect of smoking appears to be weaker, and the evidence for an effect of alcohol is scant and inconsistent. However, epidemiologic studies consistently identify people with frequent symptoms of gastro-oesophageal reflux (GOR) as having the highest risk of OAC, but the effect of GOR on OSCC has been negligible. Furthermore, it has been argued that adenocarcinoma occurring at the gastro-oesophageal junction (GOJAC) may have different aetiology again. Together, these reports suggest the three subtypes of oesophageal cancers (OAC, GOJAC and OSCC) may arise through different mechanisms with different strengths in the impact of risk factors. This thesis investigated the independent associations of smoking, alcohol and gastro-oesophageal reflux on cancers of the oesophagus by considering the possibility of variation in the risks due to differences in the dose effect patterns of various measures such as smoking, alcohol and GOR. Method Data from a population-based case-control study of oesophageal and ovarian cancers in Australia were used. Study participants comprised histologically confirmed cases of OSCC (n=308), OAC (n=367) and GOJAC (n=426) who were frequency matched to 1580 controls from the general population. Exposure history for both cases and controls were derived from health and lifestyle questionnaires. Unconditional multivariate logistic regression was used to calculate the odds ratios and 95% confidence intervals for the risk factors analysed. In addition, generalised additive model with a logit link was also used to explore and present the non-linearity in the dose effect pattern for continuous exposures adjusting for other confounding factors. The effects of two exposures combined on these cancers were assessed by obtaining synergy index. Results Smokers were at significantly higher risk of all three subtypes of oesophageal cancer with the risk greatest for OSCC. The effect of smoking was greater for adenocarcinoma occurring at the gastro-oesophageal junction compared to that of the oesophagus. Of the various measures of smoking, duration was significantly associated with all three subtypes of cancer whereas intensity was associated with only OSCC and GOJAC and the dose effect was non-linear. Time since quitting was associated with a steady decline in risk of all three cancers emphasising the health benefits of quitting among smokers. Alcohol was not associated with OAC or GOJAC but was significantly associated with OSCC among those drinking in excess of 170g/week. The association between alcohol and OSCC was modified by smoking; the association with alcohol was significantly greater among current smokers with effect. Low to moderate wine consumption was associated with significant risk reduction for all three cancers compared to non-drinkers. Increased frequency of GOR symptoms was associated with increased risks of OAC and GOJAC, although the risk of OSCC was constrained to frequent GOR symptoms only. The effect of GOR symptoms were exacerbated by smoking whereas it was weakened by regular NSAID use. Lastly, the sensitivity analysis that assessed the effect of non-participation among controls in the estimated effect of smoking and BMI (the two risk factors most likely to be affected by non-participation) showed a slight overestimation of effect of smoking assuming higher exposure rate among non-participants but not BMI while the effect remained strong and statistically significant. Conclusion Smoking, alcohol and GOR symptoms were the environmental factors strongly associated with all subtypes of oesophageal cancers. However, the dose effect patterns of these exposures varied by cancer subtypes. Smoking and alcohol were the larger contributing factors for OSCC whereas smoking and GOR symptoms had greater impact on OAC and GOJAC. Low to moderate wine consumption and regular NSAID use reduced the risk of all three subtypes significantly. While selection bias may have led to mildly inflated risks for smoking, the effects persisted even when modelled under extreme scenarios of biased participation amongst controls, and there was no evidence that selection bias materially affected the other associations.

ABSTRACT Background Oesophageal cancer has a high mortality; it is the 6th most common cause of death due to cancer worldwide. Of the common subtypes of oesophageal cancer, it is the adenocarcinomas that have been rising rapidly in incidence throughout the western world. The incidence of adenocarcinomas now exceeds the previously common squamous cell carcinoma. These recent changes in the incidence patterns of oesophageal cancer suggests that the environmental risk factors associated with these subtypes differ, and that changes in the prevalence of these exposures over time are the most likely explanation for the observed shifts in the incidence. However, due to its low incidence until a few decades ago, the adenocarcinoma subtype has been less studied compared to squamous cell carcinoma, and the environmental factors associated with this cancer have not been so clearly defined. Smoking and alcohol have been the strongest environmental risk factors reported for oesophageal squamous cell carcinoma (OSCC) whereas for oesophageal adenocarcinoma (OAC), the effect of smoking appears to be weaker, and the evidence for an effect of alcohol is scant and inconsistent. However, epidemiologic studies consistently identify people with frequent symptoms of gastro-oesophageal reflux (GOR) as having the highest risk of OAC, but the effect of GOR on OSCC has been negligible. Furthermore, it has been argued that adenocarcinoma occurring at the gastro-oesophageal junction (GOJAC) may have different aetiology again. Together, these reports suggest the three subtypes of oesophageal cancers (OAC, GOJAC and OSCC) may arise through different mechanisms with different strengths in the impact of risk factors. This thesis investigated the independent associations of smoking, alcohol and gastro-oesophageal reflux on cancers of the oesophagus by considering the possibility of variation in the risks due to differences in the dose effect patterns of various measures such as smoking, alcohol and GOR. Method Data from a population-based case-control study of oesophageal and ovarian cancers in Australia were used. Study participants comprised histologically confirmed cases of OSCC (n=308), OAC (n=367) and GOJAC (n=426) who were frequency matched to 1580 controls from the general population. Exposure history for both cases and controls were derived from health and lifestyle questionnaires. Unconditional multivariate logistic regression was used to calculate the odds ratios and 95% confidence intervals for the risk factors analysed. In addition, generalised additive model with a logit link was also used to explore and present the non-linearity in the dose effect pattern for continuous exposures adjusting for other confounding factors. The effects of two exposures combined on these cancers were assessed by obtaining synergy index. Results Smokers were at significantly higher risk of all three subtypes of oesophageal cancer with the risk greatest for OSCC. The effect of smoking was greater for adenocarcinoma occurring at the gastro-oesophageal junction compared to that of the oesophagus. Of the various measures of smoking, duration was significantly associated with all three subtypes of cancer whereas intensity was associated with only OSCC and GOJAC and the dose effect was non-linear. Time since quitting was associated with a steady decline in risk of all three cancers emphasising the health benefits of quitting among smokers. Alcohol was not associated with OAC or GOJAC but was significantly associated with OSCC among those drinking in excess of 170g/week. The association between alcohol and OSCC was modified by smoking; the association with alcohol was significantly greater among current smokers with effect. Low to moderate wine consumption was associated with significant risk reduction for all three cancers compared to non-drinkers. Increased frequency of GOR symptoms was associated with increased risks of OAC and GOJAC, although the risk of OSCC was constrained to frequent GOR symptoms only. The effect of GOR symptoms were exacerbated by smoking whereas it was weakened by regular NSAID use. Lastly, the sensitivity analysis that assessed the effect of non-participation among controls in the estimated effect of smoking and BMI (the two risk factors most likely to be affected by non-participation) showed a slight overestimation of effect of smoking assuming higher exposure rate among non-participants but not BMI while the effect remained strong and statistically significant. Conclusion Smoking, alcohol and GOR symptoms were the environmental factors strongly associated with all subtypes of oesophageal cancers. However, the dose effect patterns of these exposures varied by cancer subtypes. Smoking and alcohol were the larger contributing factors for OSCC whereas smoking and GOR symptoms had greater impact on OAC and GOJAC. Low to moderate wine consumption and regular NSAID use reduced the risk of all three subtypes significantly. While selection bias may have led to mildly inflated risks for smoking, the effects persisted even when modelled under extreme scenarios of biased participation amongst controls, and there was no evidence that selection bias materially affected the other associations.

ABSTRACT Background Oesophageal cancer has a high mortality; it is the 6th most common cause of death due to cancer worldwide. Of the common subtypes of oesophageal cancer, it is the adenocarcinomas that have been rising rapidly in incidence throughout the western world. The incidence of adenocarcinomas now exceeds the previously common squamous cell carcinoma. These recent changes in the incidence patterns of oesophageal cancer suggests that the environmental risk factors associated with these subtypes differ, and that changes in the prevalence of these exposures over time are the most likely explanation for the observed shifts in the incidence. However, due to its low incidence until a few decades ago, the adenocarcinoma subtype has been less studied compared to squamous cell carcinoma, and the environmental factors associated with this cancer have not been so clearly defined. Smoking and alcohol have been the strongest environmental risk factors reported for oesophageal squamous cell carcinoma (OSCC) whereas for oesophageal adenocarcinoma (OAC), the effect of smoking appears to be weaker, and the evidence for an effect of alcohol is scant and inconsistent. However, epidemiologic studies consistently identify people with frequent symptoms of gastro-oesophageal reflux (GOR) as having the highest risk of OAC, but the effect of GOR on OSCC has been negligible. Furthermore, it has been argued that adenocarcinoma occurring at the gastro-oesophageal junction (GOJAC) may have different aetiology again. Together, these reports suggest the three subtypes of oesophageal cancers (OAC, GOJAC and OSCC) may arise through different mechanisms with different strengths in the impact of risk factors. This thesis investigated the independent associations of smoking, alcohol and gastro-oesophageal reflux on cancers of the oesophagus by considering the possibility of variation in the risks due to differences in the dose effect patterns of various measures such as smoking, alcohol and GOR. Method Data from a population-based case-control study of oesophageal and ovarian cancers in Australia were used. Study participants comprised histologically confirmed cases of OSCC (n=308), OAC (n=367) and GOJAC (n=426) who were frequency matched to 1580 controls from the general population. Exposure history for both cases and controls were derived from health and lifestyle questionnaires. Unconditional multivariate logistic regression was used to calculate the odds ratios and 95% confidence intervals for the risk factors analysed. In addition, generalised additive model with a logit link was also used to explore and present the non-linearity in the dose effect pattern for continuous exposures adjusting for other confounding factors. The effects of two exposures combined on these cancers were assessed by obtaining synergy index. Results Smokers were at significantly higher risk of all three subtypes of oesophageal cancer with the risk greatest for OSCC. The effect of smoking was greater for adenocarcinoma occurring at the gastro-oesophageal junction compared to that of the oesophagus. Of the various measures of smoking, duration was significantly associated with all three subtypes of cancer whereas intensity was associated with only OSCC and GOJAC and the dose effect was non-linear. Time since quitting was associated with a steady decline in risk of all three cancers emphasising the health benefits of quitting among smokers. Alcohol was not associated with OAC or GOJAC but was significantly associated with OSCC among those drinking in excess of 170g/week. The association between alcohol and OSCC was modified by smoking; the association with alcohol was significantly greater among current smokers with effect. Low to moderate wine consumption was associated with significant risk reduction for all three cancers compared to non-drinkers. Increased frequency of GOR symptoms was associated with increased risks of OAC and GOJAC, although the risk of OSCC was constrained to frequent GOR symptoms only. The effect of GOR symptoms were exacerbated by smoking whereas it was weakened by regular NSAID use. Lastly, the sensitivity analysis that assessed the effect of non-participation among controls in the estimated effect of smoking and BMI (the two risk factors most likely to be affected by non-participation) showed a slight overestimation of effect of smoking assuming higher exposure rate among non-participants but not BMI while the effect remained strong and statistically significant. Conclusion Smoking, alcohol and GOR symptoms were the environmental factors strongly associated with all subtypes of oesophageal cancers. However, the dose effect patterns of these exposures varied by cancer subtypes. Smoking and alcohol were the larger contributing factors for OSCC whereas smoking and GOR symptoms had greater impact on OAC and GOJAC. Low to moderate wine consumption and regular NSAID use reduced the risk of all three subtypes significantly. While selection bias may have led to mildly inflated risks for smoking, the effects persisted even when modelled under extreme scenarios of biased participation amongst controls, and there was no evidence that selection bias materially affected the other associations.