Background Excess adiposity in adulthood is an established risk factor for several types of cancer, including colorectal, estrogen receptor (ER)-positive postmenopausal breast, and endometrial cancers. Dysregulated adipocytokine production and chronic low-grade inflammation, insulin resistance and hyperinsulinemia, and alteration in levels of sex-steroid hormones are three of the mechanisms hypothesised to explain the effect of adiposity on cancer risk. Current evidence suggests that these mechanisms are interconnected, and their relative importance is likely different for different cancers. Mediation analysis is a statistical method for quantifying how much of the effect of an exposure (adiposity) on an outcome (cancer incidence) is explained by a mediator (an intermediate mechanism). Recent methodological advances in this area allow assessment of mediation in the presence of multiple dependent mediators and are of great use in unravelling mechanisms linking adiposity to cancer risk. This thesis took advantage of these methods and data from four existing prospective studies to provide a comprehensive investigation of the role of the three putative pathways in explaining the effect of adiposity on the risk of colorectal, ER-positive postmenopausal breast, and endometrial cancers. Methods The UK Biobank cohort was used to investigate the mediating roles of measured biomarkers on inflammatory status (C-reactive protein (CRP)), insulin signalling (glycated haemoglobin), and sex steroid hormone (sex hormone binding globulin (SHBG) and testosterone) pathways in explaining the effect of adiposity on colorectal cancer risk in men and postmenopausal women. Sequential mediation analysis was used to estimate the natural indirect (NIE) and direct (NDE) effects. A case-cohort study within the Melbourne Collaborative Cohort Study (MCCS) was used to investigate the mediating roles of fasting insulin and calculated free estradiol in explaining the effect of adiposity on ER-positive postmenopausal breast cancer risk. A regression-standardisation approach was used to estimate the interventional indirect (IIE) and direct (IDE) effects. A case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) was used to investigate the mediating roles of biomarkers on inflammatory status (captured by a panel of pro- and anti-inflammatory adipocytokines and cytokines), C-peptide, and estrone and calculated free estradiol in explaining the effect of adiposity on endometrial cancer risk in postmenopausal women. The NIEs and NDE were estimated using sequential mediation analysis. Finally, a case-cohort study within the Women’s Health Initiative Observational Study (WHI-OS) was used to investigate the mediating roles of biomarkers on inflammatory status (a panel of pro- and anti-inflammatory adipocytokines and cytokines), fasting insulin, and total estradiol in explaining the effect of adiposity on the risk of colorectal, ER-positive breast, and endometrial cancers in postmenopausal women. The IIEs and IDE were estimated using a regression-standardisation approach. Results The analysis of the UK Biobank data provided evidence for a small mediating role for CRP as well as for SHBG and testosterone (combined and beyond the potential influences of CRP and HbA1c on SHBG and testosterone levels), but no evidence of mediation through HbA1c in explaining the effect of adiposity on colorectal cancer risk in men. In postmenopausal women, there was evidence for a small mediating effect through CRP, but no evidence for mediation through HbA1c or SHBG and testosterone combined. For both men and women, a large part of the effect of adiposity on colorectal cancer risk remained unexplained by the biomarkers included in the analysis. In the MCCS case-cohort study of adiposity and ER-positive postmenopausal breast cancer, moderate to strong mediation was observed through free estradiol. The point estimate was also suggestive of weak mediation through fasting insulin, but there was high uncertainty around the estimated indirect effect. In the case-control study nested within the EPIC there was evidence for moderate mediation through inflammatory status. There was also a suggestion for weak mediation through C-peptide (excluding the potential influence of inflammatory status on C-peptide levels) and weak to moderate mediation through free estradiol and estrone (excluding the influences of inflammatory status and C-peptide on sex-hormone levels), but there was high uncertainty around the estimated indirect effects. In the WHI-OS case-cohort study of postmenopausal women, for colorectal cancer there was high uncertainty around the estimated mediating effects for all pathways, precluding the possibility of making a definitive judgement about presence and strength of mediation through the assessed biomarkers. For ER-positive breast cancer, a strong mediating effect was observed through fasting insulin and a weak to moderate mediation for estradiol, but there was high uncertainty around the estimated indirect effect through inflammatory status. For endometrial cancer, a moderate mediating effect through estradiol was observed, but there was high uncertainly around the estimated indirect effects for inflammatory status and fasting insulin. Conclusion This thesis offers an investigation of the mediating roles of inflammatory status, insulin resistance and hyperinsulinemia, and sex-steroid hormone pathways in explaining the effect of adiposity on the risk of colorectal cancer in men and postmenopausal women, and ER-positive breast and endometrial cancer in postmenopausal women. Findings from this research need to be replicated by studies ideally with larger sample sizes and repeated measures for adiposity and biomarkers, and as has been performed in this thesis, proper application of causal mediation analysis approaches to take the dependence between biomarkers into account.

Background Establishing healthy dietary intakes in childhood is important for growth, development and the prevention of overweight/obesity and many non-communicable diseases such as dental caries. There is a lack of longitudinal data on children’s dietary intake between birth and five years. A substantial proportion of Australian children are regularly cared for by their grandparents, yet there is little research exploring the influence of this environment on child health. The aim of this thesis is to describe what young children are eating across the first five years of life and examine the role that informal care, particularly grandparent care, plays in the promotion of nutrition and oral health behaviours in early childhood. Methods This thesis was guided by socio-ecological models of health and comprises four studies: 1. Examining the validity and reliability of a food frequency questionnaire (FFQ) for use with young children and pilot testing new context of eating questions (quantitative, primary data collection); 2. Exploring food and beverage consumption in Victorian children between 6 months and five years of age (secondary analysis of data from an existing birth cohort study); 3. Examining dietary intake and oral health/hygiene behaviours in three to four year old children and the association with attending formal and/or informal care (secondary analysis of data from an existing birth cohort study); 4. Exploring the role of the grandparent care environment in the promotion of nutrition and oral health behaviours (qualitative interviews with parents and grandparents). Results The FFQ is reliable and valid for use at a group rather than individual level however, the context of eating questions require further development. Discretionary foods are observed in the diets of children as early as six months of age and become more common as children get older. Living in a regional area, having an older parent or parent with high fruit and vegetable intake was associated with more frequent consumption of core foods between 6 months and 5 years of age. A socio-ecological model demonstrating the range of factors which influence nutrition and oral health in the grandparent care environment was developed. Communication between family members, knowledge, past experience and perception of roles are key influences on nutrition and oral health in this environment. Conclusion This PhD research contributes new knowledge about the dietary intakes of young children in Australia and the influence of grandparent care on dietary intake and oral health care behaviours. Early introduction and consumption of discretionary foods and drinks has ongoing implications for a range of health issues including dental caries, overweight and obesity. Dietary intake and oral health behaviours in young children are influenced by a complex mix of factors across different socio-ecological and physical environments. Grandparent care is one such environment where provision of food and oral health behaviours are influenced by a range of factors and are underpinned by the relationship dynamics within a family. Opportunities exist for further research and health promotion interventions involving grandparents.

Cerebral palsy (CP) is the most common physical disability in children in Australia and other high-income countries (Reid et al., 2016; Shaunak & Kelly, 2017). CP has permanent consequences across many areas of life from children’s early development throughout the lifespan. In research and health service settings, quality of life (QOL) is recognised as a useful conceptual model for measuring subjective wellbeing across many areas of life, including those that may be impacted by various health conditions. Generic measures aim to capture QOL for all people, while condition-specific measures have been developed to address specific aspects of life that may be affected by specific conditions, such as CP. Four CP-specific measures of QOL have been developed for children, but there are shortcomings in both current conceptual understandings of QOL for children and in these measures, particularly in their inclusion of the views of children themselves. This thesis aimed to develop a constructivist grounded theory of QOL for children with CP including the views of children with CP and of their parents, and to compare this to the content of CP QOL-Child (Waters et al., 2006), an existing condition-specific measure of QOL for children with CP. In-depth, open-ended interviews were conducted with 18 families of children with varying severity of CP, including 19 parents of children aged five to 12 years. Eight of the children aged nine to 12 years with mild or moderate CP also completed individual interviews. Interview topics ranged over many facets of child and family life, focussing on aspects that were beneficial or a hinderance to a good child QOL. Interviews were analysed using constructivist grounded theory methods proposed by Charmaz (2014). These methods are appropriate to research focusing on understanding lived experiences of participants and led to developing QOL theory that centred child and parent perspectives. Child interviews used a flexible child-friendly approach, including multiple strategies such as visual prompts and drawing materials. The use of multiple strategies contributed to child engagement and added to the richness of the data gathered, both in children’s responses to the interviews and in the process of analysis. Analysis of child interviews included examining interactions within the interview, which helped to expose disability-specific assumptions and identities. Overall, child and parent findings mirrored the same main contributors to child QOL, with some exceptions. Children provided greater insight into the complex impacts of social relationships on their QOL, while parents provided detail of wider family functioning that children may be unaware of, such as managing finances and balancing time between childcare and other responsibilities. For both children with CP and their parents, children’s QOL was the result of interactions between person and environmental factors, including issues of accessibility and inclusion. Through relationships with family members, peers, teachers, aides, and other adults in their lives, children negotiated for adaptations to overcome environmental barriers and achieve QOL goals. For parents, supporting child QOL began from the time of diagnosis, and included day-to-day management as well as future considerations for themselves, their children, and other family members. Parents worked towards good QOL for their children through hierarchical tasks, from basic care needs, to participation goals, to future considerations and advocating for systemic change. The interactions between individual personal factors and environmental circumstances reflected in the findings support socio-ecological underpinnings of QOL definitions, and social models of disability. QOL research for children with disabilities would benefit from improved conceptual models of QOL that include disability models and are based on child data for child self-report measurement models, with parent report encompassing family QOL concepts.

In address the burden of non-communicable diseases (NCDs) and achieve the universal health coverage, China officially launched the New Health System Reform in 2009. This thesis investigated trends and socioeconomic inequalities in the healthcare utilisation and financial protection among patients with NCDs in China, using two nationally representative datasets. The findings are useful for evaluating the performance of reformed health system and provide a complete picture for thinking about the socioeconomic disparity in healthcare for NCDs and multimorbidity in China.

For Indigenous peoples, community-controlled health services are a key means by which communities exert control in the planning, development and delivery of primary health care services and represent an avenue to ensure that health policy and services reflect Indigenous values and an understanding of their health needs. Sustainable implementation of community-controlled health services is strongly dependent on the existence of supportive policy, as well as a health system that is open, flexible and able to respond to external input. However, assessments of participatory health initiatives frequently examine the features of the initiative or program with minimal consideration of how the wider policy environment affects participatory processes. The current study examines the influence of local and distant factors on the effectiveness of Indigenous community-controlled health centres as participatory mechanisms, including interactions between international and domestic legislation and policy. Additionally, the research explored the applicability of lessons learned from countries’ experiences in Indigenous community participation in health to other international contexts. Case studies were undertaken with two Mapuche community-controlled health centres in Chile in order to gain perspective on the day-to-day workings and decision-making processes of the health centres. Interviews were also conducted with Ministry of Health personnel to provide a comprehensive picture of Indigenous health policy and stakeholders’ perspectives. Evidence from international experiences was then used to contextualise the Chilean findings and provide some guidance for strengthening Indigenous community participation in health both in Chile and internationally. Mapuche health administrators cited the existence of a wider system that was extremely resistant to external influence and ‘blind’ to Mapuche health as a key barrier to their work. As a result, Mapuche health centres were highly restricted in terms of their capacity to respond to local priorities and needs, even as staff considered the centres as potential vehicles for increased Mapuche political power within the health system. One of the primary aims of Indigenous community control, increased autonomy and self-determination, was thereby curtailed. Overall, the evidence indicates that international legislation alone carries little weight in facilitating consultation or engagement with Indigenous communities; however, these instruments can provide guidance to countries for the alignment of domestic policy with established principles. Such alignment both enables countries to adopt international agreements and subsequently facilitates implementation of the relevant principles and obligations. The research makes the case for approaches to Indigenous health policy that are undertaken with an eye towards building cohesion between legislation and policy across all levels to support engagement with Indigenous peoples. In conjunction with stronger political representation, incorporating the principles of reciprocal accountability into contractual agreements between the State and Indigenous health centres could support a shift towards relationships that are more equitable, provide greater stability for Indigenous health centres and facilitate increased latitude to respond to their communities’ needs appropriately. Analysis of Indigenous health policy, programs and services that takes a holistic perspective of the international, national and community-level factors impacting implementation would support decision-making in this area.

Disasters are highly disruptive events that have the capacity to result in a wide range of complex, interconnected and compounding impacts for those affected. Disaster recovery is an under-researched but developing field. While much of the recovery research to date has examined disaster impacts in isolation to each other, those affected by disasters face a multiplicity of impacts simultaneously. Additionally, the voices of those with lived experience have often been missing from existing research. To address this, this study took a deliberately broad approach, asking people affected by disasters what they considered to be helpful and unhelpful in their recovery. A constructivist, qualitative approach underpinned the study. A novel data collection method was used, where participants were asked to write a letter to themselves about what they found to be helpful and unhelpful in their recovery. A second phase of the study explored participants’ research experience. Following an overview of relevant literature, this thesis first reports on the background and methodology of the study, and then presents the results as five separate papers, each addressing the main research findings. The first finding is that people affected by disasters have a wide range of conceptualisations of what recovery means. The second is that there was a range of things participants found to be helpful and unhelpful after disasters, but broadly they could be linked to existing principles, with practical implications for future disasters. The third finding is that a hierarchy of affectedness is formed in the aftermath of disasters, and an expansion of existing models to explore this concept is presented. The fourth paper investigates the experience of people holding dual roles in recovery; being employed as recovery workers while also being personally impacted by the disaster. These individuals offer a unique perspective on experiences of recovery. The final paper presents findings related to experiences of participating in research on potentially distressing events with an unusual data collection method. Implications for policy, practice and future research are identified, with a strong focus on how support to those impacted by disasters can be improved.

Background: Asthma affects people of all ages and is associated with a substantial impact on both the individual and the community, yet there are few effective strategies to prevent its development or persistence. This is because the aetiology of asthma and factors influencing its progression or remission are currently poorly understood. Asthma primarily affects lung function. Progressive lung function decline associated with asthma is well-recognised but has not been commonly investigated as an outcome in asthma studies. Knowledge on the critical factors influencing maximal development of lung function in childhood is scarce. The development of asthma and allergic diseases is very complex and believed to be influenced by multiple genetic and environmental factors that may influence asthma risk from pre-conception through to adult life. A range of strategies modifying environmental exposures have been trialled to potentially reduce the risk of asthma, with many studies finding no evidence of substantial benefit, or only limited benefit, from the interventions. Additionally, although some genes are associated with increased asthma risk, the associations are small and only explain a small percentage of the large asthma burden. There is evidence of some gene-environmental interactions, but these relationships are varied and complex and have not yet been fully investigated or understood. Elucidating the interactions between environmental risk factors and genetic factors and their associations with respiratory outcomes in both childhood and adulthood may help identify asthma prevention strategies. The main aim of my PhD work was to investigate one group of gene-environment interactions; the relationship between oxidative exposures and antioxidant genes on asthma and lung function. Specifically, I investigated the associations between various household environmental oxidant exposures and respiratory outcomes from childhood to middle age and examined whether those associations were modified by Glutathione s-Transferase (GST) genes, which are known buffers of oxidative stress. Methods: I used a range of methods to address my research aims, including a systematic literature review and data analyses of two longitudinal cohort studies: the Melbourne Atopy Cohort study (MACS), and the Tasmanian Longitudinal Health Study (TAHS). MACS began as a randomised controlled trial investigating the effects of infant formulas at weaning and, has subsequently become a prospective birth cohort. Initially, 620 pregnant women were recruited between 1990 and 1994. The MACS children have now been followed up to 18 years of age. The TAHS is a population-based study of respiratory disease spanning from childhood to adulthood. The study began in 1968, recruiting 8,583 Tasmanian school children born in 1961 (approx. 98.8% of the Tasmanian population for 1961 births). Extensive follow-ups of initial participants were conducted in 2002 and 2012, respectively, when participants were in their 40s and 50s. Both the MACS and the TAHS collected a substantial amount of exposure and outcome data at multiple ages over the lifespan through questionnaires and clinical testing, providing a great opportunity to address questions concerning gene-environment interactions and respiratory health outcomes. I investigated the following oxidative exposures: early life tobacco smoke, early life paracetamol, heating and cooking facilities, mould, long term and current active and passive tobacco smoke. Previous evidence suggests that these common home environmental exposures are associated with increased oxidative stress, and therefore, their impacts are likely to be modified by GST genes. So, in conjunction with these exposures, I investigated potential interactions with GST gene polymorphisms at two significant developmental stages: during lung function growth in childhood and adolescence, and during lung function decline in middle age. Research Gaps: Firstly, I systematically reviewed the current evidence on interactions between indoor air pollution and GST genes in association with allergies, asthma and lung function (Aim 1: Chapter 3). I then conducted a study to examine the interactions between early life tobacco smoke exposure and GST genes on asthma and lung function in childhood and adolescence using Melbourne Atopy Cohort Study (MACS) data (Aim 2: Chapter 5). Another study on the potential interactions between paracetamol use before 2 years of age and GST genes in association with asthma and lung function in later life was performed using MACS data (Aim 3: Chapter 6). In this study, I adjusted for early life exposure to respiratory infections, an important confounding factor which has not been adjusted for by many previous studies. Finally, I conducted a study using data from the TAHS to investigate similar associations in middle-age (Aim 4: Chapter 7). In this analysis, I identified seven longitudinal exposure profiles using Latent Class Analysis (LCA) methods with common household air exposures including heating and cooking types, mould exposure, passive and active smoking. I then determined the associations between these risk profiles and respiratory outcomes, and whether these profiles were modified by GST genes. Linear and logistic regression were used to investigate these associations. Results: Aim 1. My systematic review of the relationship between indoor air pollution, GST genes and asthma identified 22 eligible studies, with 15 finding some evidence of gene-environment interactions. Overall, carriers of GSTM1/T1 null and GSTP1 Val105 genotypes exposed to indoor air pollution, were more susceptible to developing asthma and reduced lung function. However, these findings were more consistent in studies of children compared to studies of adults (Chapter 3). Aim 2. I found evidence that early life tobacco smoke exposure was associated with an increased risk of asthma, reduced lung function growth between 12 and 18 years, and reduced lung function at 18 years, with girls appearing to be more susceptible than boys (master research program). I also found an interaction between early life tobacco smoke exposure and GST genotypes on lung function at both 12 and 18 years. Carriers of GST null mutations and GSTP1 Ile/Ile alleles were more susceptible to tobacco smoke in early life, and these associations were not found in carriers of other GST genotypes (Chapter 5). Aim 3. I found some evidence that early life paracetamol use may be associated with impaired lung function and increased risk of asthma in adolescence after adjustment for the frequency of early life respiratory tract infections. Interaction analysis suggested that these associations were only for carriers of GSTM1 null and GSTP1 Ile/Ile genotypes, I did not find evidence for carriers of other GST genotypes (Chapter 6). Aim 4. I found that the exposure profiles of “Wood heating”, “All gas”, “Wood heating/smoking” and “Wood heating/gas cooking” were associated with persistent asthma and greater lung function decline by age 53 years. Carriers of GSTP1 Ile/Ile genotypes had a greater risk of asthma at age 53 years with exposure to “All gas” and “Wood heating/smoking” compared to a reference group (reverse cycle air conditioning, electric cooking and no smoking). Carriers of GSTM1 null and GSTP1 Ile/Ile genotypes had a greater risk of accelerated lung function decline when exposed to “Wood & gas heating/gas cooking/smoking” and “Wood heating/gas cooking” compared this reference group. These associations were not observed in carriers of other genotypes (Chapter 7). Conclusions: My work identified several household risk factors associated with the progression of asthma, limited maximal lung function development in childhood, or accelerated lung function decline in adulthood. Additionally, this work provides evidence on interactions between household exposures and GST polymorphisms and has contributed significantly to our understanding of gene-environment interactions in relation to respiratory health. These findings highlight the importance of considering potential gene-environment interactions in studies that investigate exposures associated with lung oxidative stress. These findings have the potential to inform guidelines and preventive strategies, especially for people who are at increased risk.

Background People with disabilities in Australia experience poorer mental health than people without disability. However, the mechanisms by which disability leads to poor mental health are inadequately understood. This PhD thesis aims to form a better understanding of how people’s socio-economic circumstances influence the effect of disability acquisition on mental health. Elucidating the causal mechanisms underpinning this relationship will inform the development of effective public health and social policies to improve the mental health of people with disabilities. Methods I used data from the Household, Income and Labour Dynamics in Australia Survey – a large nationally representative longitudinal dataset – to quantify the effect of disability on mental health and to examine the socio-economic mechanisms leading from disability acquisition to poor mental health. I identified adults who acquired a disability during their participation in the survey and used data both before and after they acquired the disability to estimate the causal effect of disability on mental health. Firstly, I conducted analyses of effect modification, examining a wide range of different socio-economic factors to determine whether they influenced the magnitude of the effect of disability acquisition on mental health, using inverse probability weighting and fixed effects models to better control for confounding. Secondly, I conducted causal mediation analyses to further examine the socio-economic mechanisms leading from disability to poor mental health, using sequential mediation analysis to examine a broad range of socio-economic characteristics and an interventional mediation approach to quantify indirect effects operating through two distinct socio-economic characteristics: employment and income. Finally, I examined the indirect effect mediated by employment in greater detail, further decomposing the natural indirect effect through employment to estimate the proportion attributable to interaction, mediation and their joint effects. Results There is a clinically significant and large effect of disability acquisition on mental health. The analyses of effect modification provided evidence that the magnitude of the effect differed according to people’s socio-economic characteristics, with greater effects observed for more disadvantaged groups. The mediation analyses provided additional evidence that socio-economic characteristics contribute to the effect of disability acquisition on mental health. A third of the effect was found to be mediated by material socio-economic factors such as employment, income, wealth, financial hardship and housing characteristics, and a further investigation of the indirect effect through employment and income highlighted employment (but not income) as an important contributing factor, explaining 11% of the effect alone. Finally, further decomposition of the indirect effect through employment suggested that the mediated effect was due to interaction between disability and employment, rather than pure mediation. Conclusion The findings of this thesis highlight the importance of the social determinants of health in generating mental health inequalities. Interventions should prioritise addressing the social determinants of health to improve the mental health of people with disabilities and reduce disability-related mental health inequalities. Furthermore, the evidence that employment is a key mediator of the effect of disability acquisition on mental health indicates that policy strategies are needed to target the causes of low employment rates for people with disabilities.

Background The number of people with type 2 diabetes is increasing rapidly, particularly in low- and middle-income countries (LMICs). High and increasing prevalence of type 2 diabetes contributes to increased morbidity and mortality due to its complications, most importantly, cardiovascular diseases (CVD). Therefore, preventing type 2 diabetes is a high priority. This thesis focuses on the effectiveness of two types of lifestyle interventions that aim to prevent type 2 diabetes and reduce CVD risk by reducing underlying modifiable lifestyle risk factors. The interventions include 1) community-wide lifestyle interventions that target the whole population living in a particular geographic area and 2) structured lifestyle interventions among individuals at high risk of developing type 2 diabetes based on a screening tool. Aims The overarching aim of the current thesis is to assess the effectiveness of lifestyle intervention programs in the prevention of type 2 diabetes and the reduction of cardiovascular diseases risk in resource-constrained settings. This thesis has three main objectives to address its overarching aim: i) To evaluate the effectiveness of a community-wide lifestyle intervention on the prevention of type 2 diabetes in a trial conducted in Iran (Chapter 4), ii) To evaluate the performance of different screening methods in identifying those at high risk of type 2 diabetes (Chapters 5 and 6), iii) To evaluate the effects of a structured lifestyle intervention on the reduction of CVD risk among individuals at high risk of developing type 2 diabetes in a cluster-randomized trial conducted in India (Chapter 7). Methods To meet the study objectives, I conducted a secondary analysis to datasets of two lifestyle intervention trails entitled “Tehran Lipid and Glucose Study (TLGS)” and “Kerala Diabetes Prevention Program (KDPP)”: In TLGS, three areas in District 13 of Tehran, the capital city of Iran, were selected for the study. People living in one area received a multi-component community-wide intervention including an educational session in a medical health centre, newsletters and health education materials four times a year and public education in community gatherings from 1999 until 2015. People in the other two areas were assigned to the control status. People in all three areas were followed up every three years, from 1999 until 2015 (Wave 1 to Wave 5). In KDPP, 60 randomly-selected polling areas in the Kerala state (India) were screened by a non-invasive risk score entitled “Indian Diabetes Risk Score (IDRS)”. Those with IDRS score of >=60 were recruited in the KDPP study if they did not have type 2 diabetes in an oral glucose tolerance test. Identified high-risk individuals in 30 randomly-selected polling areas were assigned to the lifestyle intervention and their counterparts in the other 30 polling areas were assigned to the control. People in the intervention group received 15 group sessions delivered over 12 months. High-risk individuals in both intervention and control groups were followed at baseline, 12 months, and 24 months. I used generalized estimating equations (GEEs) to evaluate the effectiveness of lifestyle intervention programs in the prevention of type 2 diabetes in TLGS. I also used the Framingham risk prediction model for CVD to compare the change in predicted 10-year CVD risk between intervention and control groups of KDPP study, using mixed-effect models. Moreover, I validated several non-invasive and step-wise screening methods in the control group of TLGS, and then I assessed their performance for identifying those at high risk of type 2 diabetes. Results I found that lifestyle intervention in TLGS was associated with a 28% reduction in the incidence of type 2 diabetes in short-time (i.e., 3.4 years after starting the intervention). However, there was no statistically significant and clinically meaningful reduction in the incidence of type 2 diabetes in the following waves (Chapter 4). I also showed that favourable effects of the lifestyle intervention on the reduction of smoking prevalence and improvement of diet quality maintained even in the latest follow-up wave (Chapter 4). In addition, I found that non-invasive risk prediction models have limited utility in identifying those at high risk of developing type 2 diabetes and cannot be used as the only measurement for screening in Iran (Chapter 5). However, stepwise screening methods that combine a non-invasive measurement (e.g., anthropometrics) with a lab-based measurement (e.g., fasting plasma glucose level) have acceptable performance in identifying those at high risk of type 2 diabetes. Moreover, I found that the KDPP lifestyle intervention was associated with a one percentage point reduction in the 10-year CVD risk based on the Framingham risk prediction model after 24 months. My further investigations showed that favourable effects of the intervention on CVD risk are mainly due to a reduction in the incidence of type 2 diabetes and the reduction of smoking prevalence in the intervention group as compared to the control group. Conclusions This thesis provides much-needed evidence on the effects of lifestyle intervention programs on type 2 diabetes prevention and CVD risk reduction in LMICs. Findings from this thesis also highlight the importance of selecting a valid, reliable, and accurate screening method for identifying those at high risk of type 2 diabetes in designing lifestyle intervention programs with a high-risk strategy.

Co-production is where citizens and clients actively contribute to the work of delivering public services and the production of publicly valuable outcomes. This thesis examines co-production in the care of ageing populations, as one of the greatest challenges facing 21st century governments. It comprises both theoretical and applied research at the point where two literatures, in co-production and in health and social care intersect, with important implications for policy and practice. A narrative review of the literature was conducted revealing gaps in the current analysis. From a top- down perspective, a systematic policy document analysis and key stakeholder interviews were performed, that illustrates the impact of emerging Australian health reforms on co-production. The main study of the thesis adopted a bottom-up perspective, that involved qualitative semi-structured interviews to capture the lived experiences of older people with complex needs and their carers as ‘co- producers’ of complex care in the community. This thesis provides frameworks for facilitating and sustaining the co-production of complex care that consider what influences people’s propensity to co- produce in this context and how care tasks are distributed between clients, their informal carers and the service system.

Background Common mental health problems are a rising cause of disability in the workplace. Help-seeking rates are low and there are considerable individual, social and economic impacts. One way to address the impact of mental health problems in the workplace as part of an integrated approach is to improve mental health literacy through training. An existing evidence-informed mental health literacy training program is Mental Health First Aid (MHFA). The MHFA program has a large body of evidence for improving participant mental health first aid knowledge and confidence and reducing stigmatising attitudes. Follow-up studies also indicate that participants go on to use their skills to offer assistance to others they are concerned about. The Standard MHFA course is focused on adults helping other adults and the content is informed by a series of guidelines developed through the Delphi consensus method. Given the MHFA program is widely disseminated internationally, it has good potential for uptake by workplaces wishing to train their workers in how to offer mental health first aid to co-workers. Further research is required to ensure this work is guided by evidence. This thesis aims to build knowledge around mental health first aid in the workplace setting to inform future interventions by: 1. Better understanding how the existing MHFA course is delivered in Australian workplaces and inviting feedback on how the course could be tailored for the workplace setting 2. Developing expert consensus guidelines on how to provide mental health first aid to a co-worker 3. Developing evidence-based recommendations for workplaces wishing to establish formal Mental Health First Aid Officer (MHFAO) roles. Three studies were carried out to fulfil the thesis aims. Study 1 Method The first study focused on exploring the experiences of instructors who had delivered MHFA training to workplaces. One hundred and twenty Australian MHFA instructors completed a purpose designed survey retrospectively reporting on MHFA course delivery in workplaces in the previous 12 months, including the industries, reasons for delivering training and any observed impacts after training. The survey also asked for feedback on how the MHFA course content and mode of delivery could be tailored for workplaces. Finally, instructors reported on the perceived benefits and challenges in delivering workplace training and further support they may require. Results The first study found that MHFA training in workplaces was largely concentrated within three industry areas, more often with a focus on developing skills to help clients rather than co-workers and prompted by an internal policy recommending mental health training. Instructors indicated they most wanted workplace specific content and scenarios added to the course and most endorsed face-to-face delivery to an audience of mixed role types, rather than separate training for employees and managers/leaders. A number of benefits, challenges and support needs were also identified. Study 2 Method The second study used Delphi consensus methodology drawing on the expertise of three groups of panellists from English speaking developed countries; individuals with lived experience of mental illness whilst working, managers and workplace mental health professionals. The study aimed to build consensus amongst the expert panellists on the importance of a series of mental health first aid actions in the workplace drawn from the literature to be included in a guideline document. Results A literature search yielded 246 possible helping statements. Of these, 201 items were agreed to be important or very important to be included in a guideline document by at least 80% of the panellists. These items included actions on how to approach and offer support to a co-worker and additional considerations when the person being offered first aid is a supervisor or manager, or if the person is in a crisis situation such as acute distress or intoxication. The study found that panellists found difficulty in reaching consensus on a number of items related to role delineation, privacy and assisting a person in a more senior position. Study 3 Method The final study explored the experiences of workplaces that had appointed employees trained in MHFA into formal MHFAO roles using qualitative case study methodology. Employees from five diverse workplaces with Australian sites completed semi-structured interviews on their implementation approach and the perceived benefits and challenges experienced. Results The results suggested that organisations tended to differ in their implementation approach based on the amount of experience they had with the MHFAO role. There was strong agreement across organisations on the benefits and challenges experienced with the role. Respondents across all organisations agreed it was important to offer MHFA training to all staff if feasible and identified important differences between the MHFAO role and a traditional first aid officer role. A number of recommendations for future workplaces appointing MHFAOs were developed based on the insights shared by organisational representatives. Discussion The results of these three studies provide new knowledge on mental health first aid in the workplace in a number of ways. The results from the first study highlighted that the dissemination across industries has been relatively narrow to date, suggesting that the current MHFA course may need further tailoring to enable broader reach across industries. The guidelines resulting from the second study provide clear consensus-based strategies on how to offer mental health first aid to a co-worker. There was contention on certain topics, suggesting that providing mental health first aid in a workplace context can be complex possibly due to the constraints of workplace roles and responsibilities. In collaboration with MHFA Australia, the insights provided by instructors and the guidelines have now informed the content and delivery of a tailored MHFA course for the workplace. An important finding from the third study was that organisations appointing MHFAOs found it challenging to provide adequate support to those trained in MHFA, in addition to this being the most cited area of suggested improvement by participants. This suggests that organisations may benefit from being offered guidance when planning their approach to MHFA training in the workplace. An MHFA implementation guide for workplaces has now been developed as a result of the third study. The findings from all three studies can be used to develop further relevant resources and services in order to enhance the well-established benefits of MHFA training. Future work could evaluate the guidelines as a standalone minimal intervention and refine the process of revising the guidelines so that they are more targeted for their intended use. Since this thesis research commenced, the field of workplace mental health has significantly progressed and a number of evaluations of mental health literacy interventions in the workplace have been published. These recent findings are discussed in the context of how a possible workplace specific MHFA intervention informed by the three research studies would be conducted in future. Suggestions for future evaluations include providing implementation support to organisations before and after training, including broader workplace measures to assess impact such as help-seeking behaviours and productivity within the workplace and finally, including MHFA training in an integrated workplace mental health intervention.

In 2018, 3,046 people in Australia died by suicide of whom the vast majority, 2,320 (76.2%), were men. A range of reasons have been put forward to explain the higher rate of suicide among men compared with women but perhaps underpinning all these are conformity to masculine norms. If the rate among men is to be reduced, then suicide prevention interventions are needed that adopt a gendered approach and attend to the influence of masculine norms. In Australia, the ‘dominant masculinity’ is one that endorses the norms of stoicism, independence, invulnerability and avoidance of negative emotions. Conformity to these masculine norms has been associated with suicidal thinking, poor mental health and reduced and delayed help-seeking. Evidence has been found for the mediating role of harmful masculine norms in men’s help-seeking for mental health and suicide concerns. Men demonstrate lower rates of help-seeking for mental health problems and suicidal thoughts compared to women, and help-seeking behaviour has been cited as a key target for improving men’s health. If conformity to masculine norms both confers increased risk of suicidal thinking and influences reduced help-seeking, then interventions that address masculine norms may be a fruitful avenue from a suicide prevention perspective. Little is known about how masculine norms might be targeted to improve these outcomes. The Man Up project was funded by the Movember Foundation in Australia with the intention of addressing the high suicide rate among men by promoting help-seeking for personal or emotional problems via an exploration of Australian masculinity. Man Up was a media-based population-level suicide prevention intervention, the centrepiece of which was the Man Up documentary. The documentary examined how society shapes the way men and boys see themselves and the way in which they act and explored how this might affect mental health and, potentially, lead to thoughts of suicide. It was aired by the Australian Broadcasting Corporation (ABC), Australia’s national public free-to-air broadcaster, in October 2016 and was accompanied by a digital strategy across social media and a website. The overall aim of this thesis is to examine the ways in which Man Up contributed to help-seeking by men with a view to informing future suicide prevention interventions. The thesis aims to determine whether, and how, Man Up brought about changes in men’s help-seeking via a focus on masculine norms. This aim is addressed through four papers that are incorporated into the thesis. A randomised controlled study demonstrated quantifiable changes in help-seeking intentions and conformity to masculine norms in those who viewed Man Up. Qualitative feedback demonstrated impacts of Man Up on men’s awareness of suicide and mental health problem, others’ emotional lives, willingness to help others, and openness about emotions and problems, as well as behavioural changes related to helping others and being more emotionally expressive. In an in-depth analysis of feedback provided through the trial and the website survey regarding the impacts of Man Up on men’s views of masculinity, participants commented they had rethought stereotypes of masculinity and considered the inclusion of a wider diversity of attitudes and behaviours in relation to ‘being a man’. An evaluation of the website, website survey and emails to the website demonstrated that the website provided an important opportunity for people to engage with Man Up and seek help. These findings indicate that Man Up had positive impacts on men’s help-seeking and conformity to harmful masculine norms. It is likely that Man Up had significant population-wide positive impacts when it was delivered as a multimedia intervention in late 2016. The thesis demonstrates the importance of focusing on masculine norms to bring about improvements in men’s help-seeking and the media is highlighted as a valuable tool to be harnessed to this end. Strategies and associated actions for future help-seeking interventions for men are made based on the Theory of Planned Behaviour, and avenues for further research are recommended. Key among the strategies, and perhaps underpinning them all, is attention to changing men’s conformity to masculine norms that discourage help-seeking and emotional expressiveness, and the need for a community that is supportive of men’s help-seeking. Further research regarding the sustainability of change in these domains is also needed. These suggestions for future interventions and research have the potential to further improve men’s help-seeking and ultimately may contribute to reduced suicides by men.