Melbourne School of Population and Global Health - Theses

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    Economic analysis of next-generation sequencing for blood cancers: informing policy decision-making towards reimbursement
    Vu, Martin Viet Huy ( 2023-12)
    Next-generation sequencing (NGS) technologies constitute a range of methods that can perform genomic analysis of blood cancers, and therefore aims to establish precision therapies and enhance health outcomes in affected individuals. There is considerable enthusiasm surrounding the integration of NGS into healthcare practices and advocacy for its reimbursement as a genomic test. However, achieving routine reimbursement necessitates the development of sufficient and appropriate evidence showcasing its value for healthcare systems. This involves meeting the regulatory criteria set by health technology assessment (HTA) agencies, which stipulate that the intervention must be efficacious, safe, cost-effective, and more efficient than existing standard-of-care practices. Unfortunately, the existing evidence regarding the health economics outcomes of NGS technologies for blood cancers on healthcare systems is currently limited and may not be fit-for-purpose for the practical application of these precision medicine diagnostics for patients with blood cancer. This thesis aims to bridge the current economic evidence gap by evaluating the health economics implications of NGS technologies for the management of blood cancers at various stages of patient clinical care and learning from these assessments to develop a general framework for assessing the health economics value of NGS technologies for patients with blood cancer in Australia. To achieve these aims, this thesis encompasses four distinct studies. The first study reviewed health economics literature for molecular biomarker tests, encompassing NGS, and identified a research gap where various applications of NGS in blood cancers are yet to be explored in terms of their potential health economics outcomes. All subsequent studies from this thesis sought to remedy this lack of research. The second study evaluated the cost-effectiveness of a targeted NGS gene panel designed to identify patients who would respond optimally to a specific first-line novel treatment in chronic lymphocytic leukemia (CLL). This case study was selected for its significance as an NGS application supported by robust clinical evidence and recommendations. However, targeted NGS proved not to be a cost-effective intervention, aligning with the cost-effectiveness concerns associated with the guided treatment being considered either non-cost-effective or excessively expensive. Moving forward, the thesis examined into another application of NGS technology, specifically non-targeted NGS, acknowledging its notable clinical utility for specific blood cancer subtypes such as B-cell acute lymphoblastic leukemia (B-ALL). The third study evaluated the preferences of multiple stakeholders regarding alternative reimbursement pathways for non-targeted NGS in blood cancer. The analysis revealed that the primary drivers for reimbursement were achieving cost neutrality and ensuring accessibility. This was particularly significant when supported by robust clinical evidence and extensive variant testing, despite historical payer preferences prioritizing cost-effectiveness outcomes within an acceptable range. Expanding on the findings from the third study, the fourth study estimated the direct costs of using non-targeted NGS, specifically through whole genome and transcriptome sequencing (WGTS), within the framework of molecular subtyping as opposed to the existing routine diagnostic testing algorithm for B-ALL patients. Despite the higher additional cost of achieving another accurate molecular subtype with WGTS approaches compared to routine diagnostic testing, there is potential for cost reduction through decreased consumable expenses or improved molecular subtype classification yield. The economic analysis conducted on NGS in blood cancers throughout this thesis has presented novel evidence and initial steps towards establishing NGS as a value-for-money intervention. Recent policy developments in Australia, specifically regarding the reimbursement of a targeted gene panel for blood cancers, align with the insights from this thesis, emphasizing NGS as a favored diagnostic tool over considerations of costs and health outcomes associated with novel targeted therapies. In the case of non-targeted NGS, health economics research needs to approach and demonstrate that it does not incur additional costs or is more affordable than current diagnostic approaches to secure reimbursement.
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    Public health ‘evidence’ in Aboriginal and Torres Strait Islander health and social settings: past, present, and future
    Luke, Joanne Nicole ( 2023-07)
    Australian governments and universities are increasingly promoting evidence-based practice in Aboriginal and Torres Strait Islander settings. This practice has meant that Western evaluation and research ‘evidence’ is increasingly being applied to decision making in this setting. In recent years Indigenous scholars and communities have come to question the ethics of applying evidence-based practice within Aboriginal and Torres Strait Islander settings. Firstly, they raise concerns regarding the quality, ethical strength, and safety of the existing evidence-base, especially given the long and tarnished history of “dirty” research on Aboriginal and Torres Strait Islander people. Secondly, they express issue with contemporary Western evidence-based practice methods (including evidence hierarchies, tools and guidelines) which all privilege Western ‘evidence’ which can marginalize the expert perspectives, experiences and knowledge of Aboriginal and Torres Strait Islander community controlled organisations. In this thesis, a critical Indigenous research methodology was applied to better understand the existing evidence-base (research and evaluation) and evidence-based practice relating to Aboriginal and Torres Strait Islander people. This thesis is presented in three sections: Past In Australia, dominant universities such as the University of Melbourne have long been the sites of colonising knowledge production practices where research and evaluations have been constructed without consent, benefit or involvement through methodologies “about us, without us”. Masquerading as ‘evidence’ these knowledges have provided the logic for many social policies that have had real and devastating impacts. This review rather than focusing upon what is known about Aboriginal and Torres Strait Islander bodies, turns the gaze on research ‘experts’. Focusing on researchers from the University of Melbourne, this review describes past research methodologies and the resulting research ‘evidence’. In examining past research, this review brings attention to the everchanging socio-cultural context of research and reflects on the role that ethical reform and Aboriginal and Torres Strait Islander peoples’ self-determination has played in changing research practice and generating more ‘culturally informed evidence’. Present Research has changed dramatically with the establishment of global and national ethical reforms and guidelines. However, the contemporary public health environment is still largely characterised by an environment where qualified ‘experts’ in Australian universities and governments are powered to construct research and evaluation ‘evidence’ about Aboriginal and Torres Strait Islander people using Western research and evaluation methodologies. This section consists of three publications that evaluate and critique contemporary public health practice. These publications highlight issues with the availability, quality and ethical strength of existing research and evaluation ‘evidence’ relating to Aboriginal and Torres Strait Islander people. This research also identifies concerns with contemporary evidence-based practice environments where Western ‘experts’ and western practice methods are valued. Future: In this section, I present an Aboriginal-led epidemiological analysis, where the knowledges and experience of the community controlled sector contributed to the construction of culturally informed evidence. In this section, I also consider future public health practice, arguing that building a culturally informed evidence base and the enaction of culturally informed evidence-based practice will require Aboriginal and Torres Strait Islander people and organisations to have greater control in public health decision making.
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    Sexual Health in Australian Primary Care: How can we improve access and outcomes for young people?
    Bittleston, Helen ( 2023-12)
    Sexual health care, including the diagnosis and management of sexually transmissible infections (STIs) predominantly occurs within general practice in Australia. Young people (aged 15-29 years) are disproportionately burdened by certain sexual health issues, including STIs, and are considered a priority population group for sexual health care. In recent years, diagnoses for several STIs (namely chlamydia, syphilis, and gonorrhoea) have been increasing in Australia, with evidence of increased heterosexual transmission of syphilis and gonorrhoea. Often, these infections are asymptomatic, which can reduce the likelihood of diagnosis. When left untreated STIs can result in severe reproductive health outcomes. Syphilis has severe implications during pregnancy; for example, it can lead to spontaneous miscarriage, stillbirth, and can also be transmitted to the foetus. Untreated chlamydia and gonorrhoea can lead to pelvic inflammatory disease (PID) in women, which is associated with fertility issues and ectopic pregnancy. Timely access to sexual health care services to detect and manage infections is essential to STI control. However, young Australians may be reluctant or unable to access sexual health care due to various previously established barriers. Health care providers may also experience challenges to providing sexual health care, and diagnosing STI-related complications presents clinicians with additional challenges. This PhD sought to explore young people’s experiences of and perspectives on accessing sexual health care, taking into account the impact of the COVID-19 pandemic on accessibility. It also considered certain barriers from the provider perspective, specifically the difficulty that general practitioners (GPs) face providing pelvic examinations and diagnosing PID. The overall aim of this PhD was to explore how young people’s sexual health can be improved. Key objectives were to (i) identify which characteristics and factors impact young people’s access to sexual health care; (ii) identify gaps in young people’s sexual heath knowledge and sexual health care; (iii) understand the impact of COVID-19 on young people’s access to and experiences of sexual health care; and (iv) explore how the diagnosis of STI-related complications may be improved in primary care. To achieve the above objectives, this PhD comprised four distinct projects. The first project involved the development, distribution, and analysis of a large online survey of 16–29-year-olds living in Australia. This first project sought to explore young peoples’ sexual health attitudes, knowledge, and priorities using a mixture of qualitative and quantitative analyses. Young people were found to be generally receptive to discussing their sexual health but continued to experience key barriers to accessing care. Multivariable logistic regression identified two important and modifiable factors that were related to several outcomes; having an established clinical relationship with a GP and having received a school-based sex education were both associated with increased receptiveness to accessing sexual health care. This first project also identified that a substantial number of young people have sexual health concerns that they would like to be addressed by a GP, and hold some key STI knowledge gaps, particularly relating to syphilis. Analysis of free-text survey comments identified that there was low prioritisation of sexual health among young people, as well as misconceptions and confusion around the role of GPs regarding sexual health care. The second project within this thesis involved mixed-methods analyses of repeated online survey data collected throughout the first year of the COVID-19 pandemic. This project specifically considered how access to sexual health care was impacted by the pandemic (and its associated lockdowns). Key findings related to reasons behind young people’s delayed access to sexual health care (including, for example, fears of contracting COVID-19 and uncertainty around the allowability and appropriateness of seeking sexual health care during a pandemic) and the acceptability of Telehealth for sexual health. The third and fourth projects considered the diagnosis of STI-related complications from the health care provider perspective. The third project involved a mixed-methods secondary analysis of data from an online survey of GPs, finding that despite most GPs routinely enquiring about symptoms suggestive of PID in female patients diagnosed with an STI, there are key barriers that prevent them from providing pelvic examinations to support a diagnosis. In particular, bimanual pelvic examinations were performed less frequently when compared with speculum pelvic examinations, with several GPs reporting in free-text comments that their lack of confidence or experience with these examinations prevented them from providing these to patients. The fourth project involved interviews with health care providers and young women regarding the development of a diagnostic test for PID. Thematic analysis was utilised to determine how a test might be used by providers, and key characteristics that such a test would need to be useful and acceptable. Health care providers identified that a diagnostic test for PID would be most useful in patients with mild PID, and in some settings where decisions must be made quickly and patients may be lost to follow up. The patient experience was a very important consideration for health care providers, and young women highlighted the importance of their GPs endorsement of a test. This research has several implications. Firstly, GPs and other providers of sexual health care should be cognisant that young Australians are largely receptive to discussing their sexual health, and indeed, many have unaddressed sexual health issues or concerns that they would like to discuss. Confidentiality concerns and the prospect of intimate examinations are key barriers for young people to raise their sexual health, and this is something that GPs and other health care providers might proactively discuss with young patients to alleviate concerns. This thesis has also highlighted several areas where young people may benefit from further education or health promotion, including the importance of prioritising sexual health (even during a pandemic) and the GP’s role regarding all aspects of sexual health and preventative care. Finally, this body of research has also made clear the importance of investing in further research into the PID diagnosis support needs of primary health care providers, and supports the strengthening and expansion of school-based sex education programs, routine primary care for young people, and telehealth for uncomplicated sexual health issues.
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    Identity and resilience among Hazara and Afghan adolescents and young adults following childhood experiences of forced migration
    Shahimi, Farnaz ( 2024-02)
    In Afghanistan, prolonged conflicts have for decades forced individuals to flee. Globally, the number of forcibly displaced people rose substantially to 108.4 million in 2022. The return of the Taliban government in Afghanistan in 2021 led to a large increase in the number of people fleeing the country. Australia is among the high-income countries hosting Afghans from a refugee background. The large number of resettled children and adolescents from Afghanistan in Australia increases the need to understand how they can be supported to build resilience after the adverse experiences of the refugee journey. In the past two decades, researchers have focused on factors promoting resilience in young people from a refugee background. While research suggests that having a ‘positive sense of identity’ is a protective factor for resilience, little attention has been paid to the process of how a young person [re]constructs a positive sense of identity following experiences of trauma and displacement. Moreover, the interactions between [re]constructing a sense of identity, resilience and a young person’s sociocultural environment following refugee experiences have rarely been studied. This PhD research sought to address this gap. The project furnishes a culturally and contextually grounded understanding of perceptions of identity and resilience in Hazara and Afghan young adults and adolescents and how these perceptions interact. While most studies of identity in the context of forced migration have been conducted with adults, this in-depth qualitative study involved 10 adolescents and six parents, along with 15 Hazara young adults who migrated as children. The work incorporated a scoping review of the past two decades of studies exploring the sense of identity in young people from refugee backgrounds and empirical findings from interviews, narratives and visual elements provided by participants. The findings of the scoping review were that young people from refugee backgrounds perceived themselves as having multiple identity characteristics influenced by their interactions with their sociocultural environments and the need to integrate their past, present and future. The review emphasised the importance of holistic and pluralistic perspectives that consider factors in different layers of the social ecology for understanding how young people from refugee backgrounds shape their identities in their unique sociocultural contexts. Interviews with young Hazara adults revealed that participants perceived their identity as a life story that integrated memories from childhood with experiences of forced migration. The participants reported that traumatic incidents prior to arrival in Australia and challenging experiences in Australia constituted turning points in their lives and disclosed how suffering was translated into resilience, hope, determination, aspirations and achievements. Although this meaning-making and a personal sense of resilience comprised core elements of participants’ positive sense of identity, finding a middle ground between Hazara and Australian identity and developing a sense of belonging were loci of struggle for participants. Findings with adolescents and parents also showed that faced with the effects of current and past adverse experiences, adolescents perceived themselves as resilient, with a sense of agency and determination central to their identity. Analysis of the interviews and narratives showed the substantial effect of post-migration barriers to seeking and finding belonging on the process of [re]constructing a sense of identity. This work showed that when young people have experienced major life challenges (such as trauma and displacement), [re]construction of their identity, finding a sense of belonging and building resilience are interrelated, complex and ongoing processes. Supporting the wellbeing of young people from refugee backgrounds would require a holistic understanding of this complexity. Such an understanding can support the implementation of effective social policies and practices to provide culturally inclusive environments and support positive adjustment.
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    Understanding breast cancer via an automated mammographic measure based on textures
    Ye, Zhoufeng ( 2023-11)
    Background: Breast cancer is a significant global health concern, necessitating improved early detection and risk assessment. Mammography plays a pivotal role in the diagnosis and surveillance of breast cancer, with mammographic density being recognised as a strong risk predictor. Textural information from mammograms has emerged as a promising breast cancer risk predictor, distinct from mammographic density. However, there remains a need for comprehensive evidence to discern which of these mammographic features serves as the superior predictor for breast cancer risk and, in particular, delving into the determinants of Cirrus, a texture-based mammographic measure, which is a stronger risk predictor for breast cancer than mammographic density. Five studies were conducted to address these critical questions. Methods: This doctorate project started with a literature review comparing the predictive performance of mammographic textures and density for breast cancer risk. Three subsequent studies were based on data from the Australian Mammographic Density Twins and Sisters Study only and included investigations into the associations between Cirrus and epidemiological factors, the causal relationships between Cirrus and mammographic density defined by different brightness thresholds, and genetic and environmental influences on the variation in Cirrus. The last study was a genome-wide association study identifying genetic variants associated with Cirrus, using data from the Australian Mammographic Density Twins and Sisters Study, the Australian Breast Cancer Family Study, and the Melbourne Collaborative Cohort Study. Results: Study 1: The literature review found that out of eleven papers reporting odds ratios (ORs), six showed higher ORs for texture-based measures than percent mammographic density (P<0.05). Eleven of 17 papers showed higher the area under the receiver operating characteristic curve (AUC) of textures compared with percent mammographic density (P<0.05). The composite score of multiple textures showed the highest AUCs within the respective studies. Most papers on texture-based mammographic measures suffered from inappropriate study designs, poorly described development pipelines, and lack of transparency. Study 2: The common epidemiological factors, including demographic factors, anthropometric measures, reproductive factors, exogenous hormonal factors, disease history, and lifestyle factors, jointly explained 14% of the variance in Cirrus. After adjusting for age in Cirrus, the other factors collectively accounted for approximately 6% of the variance. Study 3: The causal inference study found evidence for both greater Cirrus and greater amounts of the light and bright areas causing greater amounts of the brightest areas (accounting for 34%, 55%, and 85% of the associations, respectively). Similarly, there was evidence for greater amounts of light and bright areas causing greater Cirrus (accounting for 37% and 28% of the associations, respectively). Study 4: For Cirrus, the familial correlations were 0.51 (standard error=0.03) for monozygotic twin pairs and 0.16 (standard error=0.03) for combined dizygotic twin and non-twin sister pairs. Additive genetic factors accounted for up to 32% (standard error=5%) of the variance in Cirrus, consistent with single-nucleotide polymorphism-based heritability estimates of 36% (standard error=12%). Environmental factors specific to monozygotic twin pairs explained up to 20% (standard error=3%) of the variance. Study 5: The lead single-nucleotide polymorphism rs11077067 on 15q21.1 of protein-coding gene SHC4 was associated with Cirrus with a p-value of 5.11E-8. Conclusion: In a mammogram, different textural features capture distinct breast cancer risk information that is partially independent of mammographic density. Certain textures could outperform mammographic density for predicting breast cancer risk. The performance could be further improved by including multiple textures. However, obtaining reliable mammographic measures based on textures for breast cancer risk prediction necessitates addressing various issues. Given that Cirrus was significantly independent of conventional epidemiological breast cancer risk factors and causally independent of mammographic density after adjusting for age, there could be distinct pathways underlying the association between Cirrus and breast cancer risk, and Cirrus has the potential to improve current breast cancer risk assessment. Cirrus is substantially familial, likely due to genetic factors and an influence of shared environmental factors, that is more evident for monozygotic twin pairs. The latter is consistent with that shared events or environment during early life or even in utero could have a significant impact on Cirrus variation. Implications: Overall, these findings have enhanced the current understanding of Cirrus, and its implications for breast cancer aetiology and risk assessment improvement, filling in the knowledge gaps in the value of texture-based mammographic measures in breast cancer.
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    Cervical cancer prevention in Japan: providing evidence for decision-making
    Palmer, Matthew Robert ( 2023-10)
    Well integrated human papillomavirus (HPV) immunisation programs, access to highly sensitive cervical screening programs, and timely access to high-quality treatment have the potential to eliminate cervical cancer globally. There are considerable deficiencies in the implementation of primary and secondary prevention strategies for cervical cancer in Japan and morbidity and mortality continues to increase. This thesis aimed to establish an evidence base to guide the development of effective HPV vaccination and cervical screening policies in Japan. It addressed this by a meta-analysis that examined the genotype prevalence of HPV, an evaluation of the diagnostic and treatment practices relating to the cervix using individual level insurance data, and a comparative cost-effectiveness evaluation. This thesis is presented as three independent studies. The rationale for this body of work is outlined in Chapter 1, which describes human papillomavirus (HPV), cervical cancer and their association with infection and increased morbidity and mortality in Japan. Japan, as a setting for studying cervical cancer prevention, is also described. The literature review also examines existing evidence for cervical cancer prevention strategies in Japan. Finally, the limitations and gaps in the evidence are described.
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    The Relationship Between Mental Health Problems and Gambling Harm
    Cameron, Lachlan Simon ( 2023-11)
    Gambling is a legal, recreational activity in many countries. It can provide benefits for some, such as enjoyment or socialisation, but can be harmful for others. Common harmful consequences of gambling include financial harm, relationship stress, and poorer health. Mental health problems, common sources of social disadvantage, are highly correlated with gambling harm. However, the causal effects and the underlying mechanisms of this relationship are poorly understood. If gambling causes mental health problems, this would indicate that gambling may create social disadvantage. If mental health problems lead to gambling harm, this would indicate that gambling may exacerbate existing disadvantage and widen social inequalities. Therefore, better understanding the causal relationships is important for informing the need for policy to reduce the effects, and better understanding the mechanisms underlying the relationship would help to identify interventions that could do this effectively. This thesis aims to improve the understanding of the relationship between mental health problems and gambling harm by exploring the causal effects and the underlying mechanisms of the relationship. It does this through a body of research covering theoretical, experimental, and econometric methods. Chapter 2 presents a new theoretical model of gambling behaviour. The model helps to identify personal characteristics that may increase the risk of gambling harm for people with mental health problems, and features of the gambling environment which may be particularly conducive to causing mental health problems. Chapter 3 presents results from a Discrete Choice Experiment mimicking online gambling on horse racing. The study finds that people with mental health problems put less thought into their bets and prefer riskier bets, two characteristics linked with a higher likelihood of developing gambling harm. Chapter 4 presents econometric analysis of spatial data with information on the location of gambling venues and residence of people who died by suicide over an 18 year period. The study finds that greater accessibility to gambling venues is associated with higher rates of suicide. Collectively, the studies in this thesis improve understanding of the relationship between mental health problems and gambling harm, and make important methodological contributions. The findings highlight higher propensity to gamble as an escape and impaired cognitive functioning as two key reasons why people with mental health problems may be more likely to develop gambling harm, and that easy access to gambling is a key feature of the gambling environment that can contribute to mental health problems. These findings have important implications for informing policy that aims to reduce the risk of gambling harm for people with mental health problems, mitigate the causal effect of gambling on mental health problems, and ultimately reduce social disadvantage.
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    Identifying interventions to prevent suicide in public places and evaluating the impact of these interventions
    Shin, Sangsoo ( 2023-12)
    Information is lacking about the extent to which suicides occur in public places, and about the factors that influence suicides in these places. There is also a lack of understanding about which interventions, other than restriction of access to means, might effectively contribute to suicide prevention in public places where suicides are frequent. This thesis comprised four studies designed to address these gaps in knowledge. Study 1 was a descriptive epidemiology study, and Studies 2-4 took the form of pre-post evaluations that assessed the population-level effectiveness of three different interventions. The aim of Study 1 was to identify the percentage of suicides occurring in public places in Australia, and to examine the socio-demographic factors associated with these suicides in public places. Study 2 sought to evaluate the effectiveness of fixed phone boxes, utilising data from six different sites (five bridges and one cliff) in Australia and the United States. Study 3 aimed to assess the effectiveness of incomplete restriction of access to means (i.e., the installation of barriers which still allowed for jumping from part of the site), using data from four bridges in Canada, South Korea, and the United States. Study 4 evaluated two interventions – a Video-based Incident Detection System (VIDS) and rolling bars – that were sequentially applied to a bridge in Korea. All data were obtained from government agencies including data managed by, or for, coroners, police, sheriffs, or national suicide prevention foundations. Study 1 indicated that 25% of suicides in Australia occurred in public places, 69% at home, and 6% in non-public places other than homes (such as institutional facilities and aged care facilities). Males had higher odds of dying by suicide in public places than females, while those who were divorced, separated, or widowed (in comparison to those married), those aged 30-54 or 55 and above (compared to those under 30), and those who were employed or not in the labour force (compared to employed individuals) had lower odds of dying by suicide in public places. Study 2 showed that since the installation of fixed phone boxes, two sites exhibited a statistically significant increase in suicides, while four other sites showed little evidence of an increase. The pooled rate ratio indicated substantial heterogeneity between the effects and insufficient evidence to conclude that there was a difference in the rate between the pre- and post-intervention periods. Study 3, which explicitly evaluated incomplete restriction of access to means, revealed significant site-specific differences in effectiveness. At two of the bridges included in the study there was a decrease in the suicide rate at the site after installation of barriers, while the rates in two other sites after installation did not differ significantly compared to the pre-installation period. Study 4 demonstrated that the installation of the VIDS increased the rate at which interventions occurred when someone engaged in suicidal behaviours before jumping but did not change the suicide rate at the site. Subsequent installation of rolling bars led to a significant decrease in the rates of both suicidal behaviours at which intervention occurred and suicide at the site. These findings indicate that suicides in public places comprise a substantial proportion of all suicides. Site-specific suicide prevention approaches in public places vary in their effectiveness, with restriction of access to means at these sites generally being more impactful than other site-based measures. However, some sites in the above studies demonstrated a significant reduction in suicide rates through interventions other than means restriction, suggesting that a carefully considered approach to implementing site-based interventions could enhance suicide prevention efforts.
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    Epidemiology of adult chronic cough
    Zhang, Jingwen ( 2023-10)
    Background: Cough is common in adults and has major impacts on individuals’ physical and mental health, and a high economic burden. Cough is a heterogenous condition and clinical guidelines recommend classifying or phenotyping cough by its duration (i.e., acute, subacute, and chronic cough) and the underlying conditions causing the cough (e.g., asthmatic cough, reflux cough, etc.). Diagnosing and treating the underlying conditions responsible for cough is often challenging, as sometimes no underlying conditions can be identified and treating the conditions may not fully resolve the cough. Therefore, using cough-related symptoms to explore heterogeneity can be simpler and more practical. Research Gaps: The heterogeneity of cough in the general adult population is poorly understood as most studies have recruited patients from cough clinics, reducing the generalisability of the findings. Furthermore, several studies have been published to investigate the longitudinal risk factors of cough in adults, but the evidence has not been systematically synthesised. There is also inadequate and inconsistent evidence on some risk factors of cough such as occupational exposures and ambient air pollution. This inconsistency may stem from the use of standard definitions of cough (i.e., chronic cough, chronic phlegm, and chronic bronchitis) which may not fully capture the heterogeneity of cough. Aim: My overall aim was to investigate the risk factors for and heterogeneity of cough in the general adult population. My specific objectives are: i) to systematically synthesise the evidence on longitudinal risk factors for adult cough; ii) to investigate the heterogeneity of cough based on cough-related symptoms (i.e., denoted as cough subclasses in my thesis) among a middle-aged population; and iii) to investigate the associations between potential risk factors and the novel cough subclasses identified in the previous objectives. Methods: My doctoral research utilised systematic review methodology and original data from the population-based Tasmanian Longitudinal Health Study (TAHS) that followed participants from age 7 to 53 years. Latent class analysis was used to identify cough subclasses in middle age based on cough-related symptoms. Clinical features of different cough subclasses were described using prevalence with logit-transformed 95% confidence intervals (CIs) and were compared using t-tests or chi2 tests. Occupational exposures were coded into a Job-Exposure Matrix (JEM) using data from participant work history calendars. Markers of ambient air pollution were derived from the residential addresses of participants using satellite-based land-use regression models. Multinomial logistic regression models were performed to assess associations between exposures and the cough subclasses, after adjusting for confounders. Logistical regression models were used for the standard cough definitions (chronic cough, chronic phlegm, and chronic bronchitis) to enable comparisons with the results from my newly identified cough subclasses. Results: In Chapter 3, I present my findings from the systematic review and meta-analysis. It found heterogeneous definitions of chronic cough used in the literature. Asthma, persistent smoking, and lower education were consistently associated with an increased risk of chronic cough in adults with little to moderate heterogeneity. There was inconsistent evidence for risk factors such as occupational exposures and ambient air pollution and substantial heterogeneity was observed across primary studies precluding any meta-analysis for these factors. In Chapter 5, I present my novel classification of six cough subclasses in a middle-aged general population using latent class analysis. Each of the cough subclasses had distinct clinical features cross-sectionally and longitudinally from childhood to middle age. The subclasses were labelled as “minimal cough”, “cough with colds only”, “cough with allergies”, “intermittent productive cough”, “chronic dry cough”, and “chronic productive cough”. In Chapter 6, I report my findings on the associations between occupational exposures and my novel cough subclasses. Specific occupational risks were identified for different cough subclasses, which were not fully captured when using standard cough definitions as outcomes. These included associations between aromatic solvents and chronic dry cough; biological dust and allergic cough; and herbicides, other solvents, and productive cough. In Chapter 7, I report my results of associations between ambient air pollution and my novel cough subclasses. There was a linear, dose-response relationship between ambient nitrogen dioxide (NO2) and productive cough (intermittent and chronic), as well as fine particulate matter with an aerodynamic diameter <= 2.5um (PM2.5) and chronic dry cough. These associations were present even in a low polluted setting as the pollution levels in this study were lower than the Australian National Environment Protection Measure. Conclusions: The identified novel cough subclasses have largely addressed the heterogeneity of cough in the community as shown by their distinct clinical characteristics cross-sectionally and longitudinally. Distinct associations between occupational exposures, ambient air pollution, and cough subclasses were uncovered, which were not detected by the standard cough definitions. Future studies should consider adopting a similar framework to address the heterogeneity of cough in general populations. This will help generate better quality evidence to inform individualised clinical management of cough.
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    Beliefs, understanding and access to male family planning methods in Timor-Leste - a participatory and operational qualitative study
    Henderson, Helen Lucy ( 2023-12)
    Abstract Background The engagement of men is essential to improving the sexual and reproductive health and rights for everyone. Effective male engagement includes increasing the availability and uptake of male family planning methods (vasectomy, male condoms and some natural family planning). The Democratic Republic of Timor-Leste (Timor-Leste) has some of the most critical sexual and reproductive health challenges in the Asia-Pacific region, including low uptake of male family planning methods. While previous studies have explored understanding of and influences upon women’s uptake of family planning methods in Timor-Leste, limited evidence exists about access to and uptake of male methods of family planning. Methods Participatory and operational qualitative research was designed and implemented to explore beliefs, understanding and access to male family planning methods in Timor-Leste from both a community and healthcare provider perspective. Fourteen participatory group discussions were held with 175 community members (84 men, 91 women; aged 18 to 72) across seven municipalities in Timor-Leste (Ainaro, Baucau, Bobonaro, Dili, Lautem, Manufahi, and Oecusse) between August - December 2019. In-depth interviews were held with 24 healthcare providers (16 women, 8 men; aged 25 to 56 years) working in the same location as the participatory group discussions. Data were analysed using reflexive thematic analysis. The ethics of reflexivity and solidarity were practiced throughout the research process. Results Community members and healthcare providers had overall low awareness and knowledge about male family planning methods and male sexual and reproductive health. Misinformation was widespread, contributing to negative attitudes about male family planning methods. Healthcare providers had limited training and experience about male sexual and reproductive health services, including male family planning services. Further, while some healthcare providers reported providing universal access to family planning, others reported restricting access based on gender, age, civil status, or number of children. Reasons for restricting access included: personal belief; misunderstandings about national health policies and laws; pressure or direction from senior health staff or colleagues; and harmful social norms regarding sexual and reproductive health and rights. Men were identified as playing a leading role in the decision to have children and a woman’s ability to access contraception by all participants. However, men were also identified as having limited interaction with healthcare services and healthcare providers. Instead, family planning services were framed as being almost exclusively about healthy birth spacing for pregnant women and mothers, delivered through maternal health services. Participants expressed interest to learn more about male family planning services, and a desire for improved access to sexual and reproductive health services more generally. Conclusion Access to male family planning services in Timor-Leste is complex and influenced by many personal, historical, socio-cultural, geographical, political, and financial factors. This study identified numerous barriers and enablers to increasing access to and uptake of male family planning methods, at the client, provider, health system and society levels. While focused on male methods of family planning, study findings are also relevant and insightful to other population groups, including young and unmarried people, and people with diverse gender and/or sexual identities. Findings indicate that Timor-Leste has a unique opportunity to design and invest in new evidence-based family planning initiatives that can better engage men, are gender transformative and are complementary to existing programs. Research findings were translated into public health practices as the study was implemented, including guiding health promotion initiatives, and informing healthcare provider training. Others working within Timor-Leste and globally can use insights from the research process and findings to inform future research, policy, and program initiatives.