Medicine & Health

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Now showing 1 - 10 of 13
  • (2020) Clare, Philip
    Thesis
    There is growing understanding that estimates of causal effects can be obtained from non-randomised studies if appropriate statistical techniques are employed, provided certain assumptions are met. However, doing so can introduce additional sources of bias that must be addressed. One such issue is that of exposure-affected time-varying confounding, where confounders of the relationship between an exposure and an outcome are themselves effected by past exposure. While methods capable of adjusting for such confounding exist, they remain underused in the literature. The thesis had two main aims: firstly, to examine and compare methods for handling exposure-affected time-varying confounding; and secondly to provide guidance on the implementation of these methods, to make them more accessible to applied researchers. The thesis presents: a systematic review of the literature of the use of the methods over a 16-year period; two simulation studies comparing different possible methods for adjusting for exposure-affected time-varying confounding, and handling missing data in analysis when such confounding is present; a tutorial on the use and implementation of targeted maximum likelihood estimation; and two applications of TMLE in the area of substance use research, an area of research which could benefit from greater use of these methods. The findings of the thesis support greater use of ‘doubly robust’ methods for causal inference in observational data. In order to promote this, it provides specific guidance on the use of TMLE, which performed well in simulations, and is also relatively easy to implement in R, using machine learning to avoid the need to manually specify models. The thesis also provides further support for the use of the models based on the findings of the applied research, which found that conclusions of TMLE models differed substantially from naïve analysis that did not account for exposure-affected time-varying confounding. Causal inference using observational data is possible, provided appropriate analysis methods are employed. Despite this, such methods have seen relatively little use in the literature, in part due to lack of familiarity and difficulty in implementation. This thesis provides evidence-based guidance on the use of the methods, and TMLE in particular, in order to make robust causal inference more accessible to applied researchers.

  • (2022) Yuen, Wing See
    Thesis
    In many high-income countries such as Australia, alcohol use has declined in young people since the early 2000s but there is conflicting evidence around reductions in alcohol-related harm. A key issue around quantifying alcohol-related harm is that different data sources can show vastly different patterns due to varying sample characteristics or methods of measurement. The studies comprising this thesis aimed to address these gaps by using a variety of data sources to examine: 1) trends in self-reported harms across age, period, and birth cohort using national surveys (n=121,281); 2) developmental patterns of blackouts, a very common harm, and predictors of high-risk patterns in a recent birth cohort (n=1,821); 3) developmental transitions between different types of alcohol-related harm and predictor of high-risk patterns in a recent birth cohort (n=1,828); and 4) risk factors for experiencing clinical alcohol-related harm for the first time at a younger age and compare rates of subsequent harm by age at first experience of clinical harm in a linked cohort (n=10,300). Several notable findings were identified. National data indicate that alcohol-related risky behaviours are much less common in recent birth cohorts, though they continue to be most prevalent in young people. Males generally had twice the prevalence of risky behaviours compared to females, but with reduced effect among more recent birth cohorts. Longitudinal cohort data indicated that escalating experience of harms, particularly blackouts and psychosocial harms (e.g., getting into fights) increased risk of early adulthood alcohol use disorder symptoms. Females were at higher risk of experiencing physiological harms such as blackouts earlier in life compared to males. Finally, analyses of linked hospital service data indicated that females were at higher risk of accessing hospital services for an alcohol-related problem for the first time at a younger age. Younger people were more likely to have subsequent injury-related ED presentations but less likely to be hospitalised. Past year hospital service access rates in this cohort were much higher than the same-aged general population. This thesis highlights important developments in young peoples’ experience of alcohol-related harm. The identification of a closing male-female gap in harms and of female status as a risk factor for early harm warrants future research and shifts to the approach of harm reduction and prevention among young people.

  • (2022) Santo Jr, Thomas
    Thesis
    Opioid use disorder (OUD) is characterised by persistent opioid use despite the experience of harm. Current literature suggests that childhood trauma and mental disorders are risk factors for illicit OUD. However, little is known about the effects of childhood trauma and mental disorders on OUD-related harm. Our understanding of this relationship is also limited by imprecise childhood trauma and mental disorder prevalence data; few studies on people prescribed opioids for chronic non-cancer pain (CNCP); and a lack of research on interventions that reduce harm related to childhood trauma and mental disorders among people with OUD. This thesis uses multiple study methods on data from several different opioid-using populations to broaden our understanding of the relationship between childhood trauma, mental disorders, and OUD. The studies in this thesis aimed to 1) estimate the prevalence of specific childhood trauma types and mental disorders among people with OUD; 2) investigate childhood trauma as an independent risk factor for OUD among a large sample of people prescribed opioids for CNCP; 3) explore the effects of childhood trauma and mental disorders on OAT engagement, crime, and mortality among people with illicit OUD; and 4) examine the associations between OAT and causes of mortality, including suicide, among people with OUD. Multiple key findings emerged from this thesis. The first two studies confirmed that people with OUD experience childhood trauma and mental disorders at far higher rates than the general population. The third study of people prescribed opioids for CNCP found that childhood trauma independently increased the risk of OUD after controlling for mental disorders and other known OUD risk factors. The fourth study found that childhood trauma and most mental disorders were related to poorer OAT engagement and higher criminal offending rates among people with OUD. The fifth study, a systematic review and meta-analysis, found that OAT was associated with reduced risk of multiple causes of mortality, including suicide, among people with OUD. Findings from these studies highlight the importance of addressing childhood trauma and mental disorders in both the treatment of OUD and the management of CNCP with pharmaceutical opioids. The results can inform clinical guidelines, policy, and future research that impact people with OUD and those prescribed opioids for CNCP.

  • (2021) James, Douglas
    Thesis
    Indigenous peoples in similarly colonised countries (Australia, New Zealand, Canada, United States of America) experience poorer health outcomes compared to their non-Indigenous counterparts. Substance use disorders are directly linked to poorer health and social and emotional wellbeing. Consequently, one response has been the development of Indigenous treatment services for substance use disorders, of which alcohol and other drug (AoD) residential rehabilitation is a key component. This thesis examines what is known about clients on admission to these services in New South Wales (NSW), Australia, and considers the relationship between clients’ intake data and their outcomes. Specifically, a PRISMA compliant systematic review was undertaken (Chapter 2) to collate the current level of published evidence on Indigenous AoD residential rehabilitation services. Chapter 3 analysed client admissions data from all six Indigenous AoD residential rehabilitation services in NSW to identify similarities and variations across services in relation to key program features (e.g., eligibility criteria, primary substance of concern, length of stay). Chapter 4, conducted across the same six services, examined admissions data and treatment outcomes to predict which clients: 1) left treatment early (≤ 28 days), 2) self-discharged or house discharged, and 3) were re-admitted to the same service within two years. The predictors were Aboriginal status, age, justice system referral and primary substance of concern. To our knowledge this is the first-time, in Australia and internationally, that data have been combined from multiple Indigenous AoD residential rehabilitation services into the same analyses and results published in the peer-reviewed literature. This thesis highlights an opportunity for policy makers and services to increase the focus of treatment towards an outcomes-based approach. However, to do so, there is a need to increase standardisation of data collection processes and the use of data in real-time, and to increase stakeholder involvement in delivering Indigenous AoD residential rehabilitation services.

  • (2022) Bosworth, Rebecca
    Thesis
    Within prison, a high prevalence of people living with human immunodeficiency virus (HIV) and opioid use disorder exist. Return to opioid use is common among people released from incarceration. Regardless of incarceration length, an estimated 85% of individuals return to opioid use within one year. Return to opioid use is associated with significant harms. Methadone may reduce return to opioid use and benefit people living with HIV and opioid use disorder due to increasing antiretroviral therapy (ART) adherence, engagement with healthcare services and reducing the risk of HIV transmission. This thesis utilises data from Project Harapan, a pre-release methadone maintenance treatment (MMT) program conducted between 2010 and 2013 in Malaysia. The overarching aim of this thesis was to explore different aspects of the pre-release MMT program among a sample of 310 men living with HIV and opioid use disorder in Malaysia’s largest male prison. This thesis comprises four studies. The first study describes the association between knowledge and attitudes and the choice to initiate pre- release MMT. Uncertainty towards methadone may be associated with MMT-related hesitancy and lower proportions of men choosing to initiate pre-release MMT. The second study uses the behavioural model for vulnerable populations as a framework to explore the association between other factors connected to healthcare utilisation and the choice to initiate pre-release MMT. Findings suggest being of Hindu faith, being prescribed (yet not taking) ART, currently being on ART during incarceration and having a more severe craving for heroin were associated with lower proportions of men choosing to initiate pre-release MMT. The third study demonstrates the impact of pre- release MMT initiation on return to opioid use following release from incarceration. The findings reveal that reductions in opioid use in the first 12 months post-release may be associated with the initiation of pre-release MMT. With HIV-related mortality closely linked with people living with HIV and opioid use disorder, the fourth study reports on a global scoping review of HIV/AIDS, hepatitis and tuberculosis-related mortality among people who experience incarceration. Globally, it remains difficult to locate good-quality infectious disease-related mortality data for prisons. Given the paucity, we located data to suggest the highest number of reported deaths over a 20-year period were attributable to HIV/AIDS (n=3,305), followed by TB (n=2,892), HCV (n=189), HIV/TB co-infection (n=173) and HBV (n=9). Increased investment to improve the reporting of key mortality indicators is urgently required. This research resulted in one published manuscript, two accepted conference abstracts and three manuscripts awaiting submission post the conference embargo period. Thesis conclusions refer to men who experience incarceration in Malaysia in a study conducted between 2010 and 2013. Globally, evidence supports the effectiveness of pre-release MMT on reducing opioid-related harms yet given the paucity of such data among men living with HIV and opioid use disorder who experience incarceration in Malaysia, no such evidence existed, and the effectiveness remained unknown. Therefore, these findings make a significant contribution to the literature in relation to this previously hidden population. This thesis demonstrates that opioid-related harms can be reduced when individuals initiate pre-release MMT. Working towards optimising MMT uptake and supporting individuals to pursue effective treatment for opioid use disorder may prevent opioid-related harms and poor HIV treatment outcomes experienced by this vulnerable population.

  • (2022) Colledge-Frisby, Samantha
    Thesis
    People who inject drugs (PWID) experience a range of clinical harms that contribute to morbidity and increase their risk of mortality. The literature has largely focused on the epidemiology of blood borne viruses (BBVs) in this population; however, other mental and physical conditions affect PWID that significantly impact quality of life. There are gaps in our understanding of the clinical profiles of PWID beyond the risk of BBVs which this thesis aims to address. This thesis employs various study designs to broaden our understanding of the clinical profiles of PWID. Firstly, three systematic reviews were conducted to synthesise the evidence and generate estimates of injecting frequency, non-fatal overdose, and mental health problems (i.e., depression, post-traumatic stress disorder [PTSD], suicidality, and non-suicidal self-harm) among PWID. Second, latent class analyses were performed using cross-sectional data from a national sentinel sample to examine profiles and correlates of PWID reporting recent injecting-related injuries and diseases (IRID). Finally, a large, linked cohort of people engaged in opioid agonist treatment (OAT) from 2001 to 2017 in New South Wales was analysed to examine the impact of OAT on hospitalisations for injecting-related diseases. Several key findings emerged from this thesis. Findings from the systematic reviews indicated that most PWID are injecting daily or more frequently and approximately one in five have experienced a recent non-fatal overdose. Fewer studies were identified that assessed mental disorders and self-harm among PWID; however, pooled estimates across studies suggested that perhaps nearly half of PWID have current severe depressive symptomology, and 22.1% have previously attempted suicide. The latent class analyses identified risk factors that may contribute to PWID experiencing more severe and multiple IRID, namely recent needle re-use and thrombophlebitis. Finally, there is a modest protective association between OAT retention and injecting-related diseases; however, hospitalisations for these diseases are increasing. These findings highlight several important areas for future research, and for clinical and public policy action. Namely, when we consider the healthcare needs of this population, we must consider this broad spectrum of pathology. Continued research into effective interventions that improve PWID health as well as expanding accessibility of existing interventions are crucial future steps.

  • (2023) Raichand, Smriti
    Thesis
    Background: Teratogenic medicines when used in pregnancy increase the risk of foetal defects. The doses above which these risks increase are published for some medicines including four antiepileptics. Among antiepileptics, valproate is associated with the highest risk of foetal harm. It is, therefore, important to understand the utilisation of teratogenic medicines among pregnant women and women of child-bearing age. Study 1 in this thesis measured the prevalence of teratogenic medicine utilisation before and during pregnancy. Study 2 estimated utilisation of teratogenic antiepileptics as average daily doses (ADDs) dispensed to women of child-bearing age. Study 3 examined valproate utilisation in pregnancy, factors associated with continuation in pregnancy, and recent trends in women of child-bearing age. Methods: In Study 1 and Study 3 we used linked administrative health records, which contained pregnancy-related details and mothers’ health service use, including dispensed prescription medicines. The cohorts comprised concessional beneficiaries who gave birth in New South Wales in 2004-2012. To examine medicine utilisation among women of child-bearing age (Study 2, Study 3) we used medicine dispensing records for 10% of the Australian population in 2012-2020. We presented prevalence as percentages and n per 1000 women, ADDs as mg/day, and associations as odds ratios (ORs). Results: The prevalence of teratogenic medicine utilisation at any time during pregnancy was 2.0%, steadily decreasing from first trimester through to birth. Teratogenic antiepileptics (carbamazepine, lamotrigine, and valproate) except phenobarbital, were dispensed at ADDs below the published high-risk dose thresholds, to women of child-bearing age. Prevalence of valproate utilisation was 5.2 in 1000 pregnant women, and approximately 24% continued use in pregnancy. Having a diagnosis of epilepsy (OR 10.2, 95% CI 5.7-18.4) was significantly associated with valproate continuation in pregnancy. Valproate utilisation among women of child-bearing age decreased from 5.8 to 3.5 per 1000 women in 2013-2020. Conclusions: Taken together, our findings on teratogenic medicine use among pregnant women, antiepileptic ADDs among women of child-bearing age and valproate exposure in these populations suggest that Australian prescribers and patients were aware of the potential harms posed by these medicines.

  • (2022) Trudgett, Skye
    Thesis
    Young people who engage in multiple risky behaviours (high-risk young people), such as substance abuse, antisocial behaviour, or suicidal ideation, are more likely to experience serious harms later in life. Despite these harms, there is extraordinarily little intervention research available to guide policy makers’ or service providers’ decision making about investing in effective programs for high-risk young people (HRYP). One potential reason for this is that most interventions available for vulnerable populations globally, are implemented by NGO’s (Non-Government Organisations) that typically lack the capacity and capability to conduct rigorous evaluation in addition to their primary service delivery roles. There is also little to no consideration given to the application of Indigenous Data Sovereignty (IDS) principles in the context of generating evidence with young Indigenous peoples. This thesis presents a range of methods that could be adopted by NGOs to design and deliver evidence-based programs for HRYP, and to explore the capacity to integrate more routine monitoring and evaluation into NGO’s delivery of those programs. This thesis seeks to demonstrate how research can be grounded in principles of IDS and considers methods for how research might best be operationalised in the context of NGO-delivered programs for HRYP. It is hoped that this approach may provide an exemplar for other programs, research projects and organisations that use data from Indigenous controlled organisations and from Indigenous peoples. The implications of the findings from this thesis, and recommendations for future research and practice implementation, are discussed. Dissemination of the methods described in this thesis will not only improve the internal capacity and capability of NGO-delivered programs to conduct evaluations in collaboration with researchers but will also increase the capacity of Indigenous peoples and communities to advocate for greater sovereignty in relation to the data and research methods with which they choose to engage. These improvements will lead to better outcomes for HRYP and their communities.

  • (2021) Hilder, Lisa
    Thesis
    Chapter 1 - Introduction. This provides an overview of mental and behavioural disorders (MBD) definitions and current knowledge about MBD in pregnancy. Maternal MBD in pregnancy are often overlooked. Most studies of MBD in pregnancy focused on a single class of MBD. This thesis used linked data from NSW Perinatal Data Collection and the NSW Admitted Patient Data Collection to assess diagnosed MBD in NSW maternities between 2002 and 2006. Chapter 2 – Methods. Describes data linkage, MBD definitions and preliminary data processing. Chapter 3 – Admissions for MBD in pregnancy. A study to compare rates of MBD admissions in pregnancy relative to MBD admissions in a baseline period. Overall, admissions for MBD were lower in early pregnancy (RR 0.71) and higher in late pregnancy (RR 1.91). Drug disorder admissions were more than 3-fold higher in late pregnancy. Schizophrenia admissions increased from early pregnancy and alcohol admissions remained lower throughout pregnancy. Baseline MBD admissions rates were higher for multiparous than primiparous maternities. Chapter 4 – Admissions with MBD in pregnancy. MBD prevalence in pregnancy was 2.4% overall, 1.4% for drug/alcohol disorders (DA) and 1.2% mental disorders (MD). Pregnancy DA prevalence was the same, psychotic disorder prevalence was half, affective disorder a third and anxiety a tenth that of comparable disorders in women of reproductive age. Coexisting MBD ranged from 23.6% for anxiety to 91.5% for sedative disorders. Smokers and residents in outer regional or more remote locations were identified as maternity populations at high risk of MBD. Chapter 5 – Neonatal outcomes. Assessed relative risks of individual classes of MBD on perinatal mortality, preterm birth, small size at birth, neonatal morbidity, and admission to neonatal intensive care (NICU). Adverse outcomes were on average 3- 4-fold higher for MBD relative to no MBD. Effects were universally attenuated by adjustment for smoking and co-existing MBD. Independent effects of opiate and cannabis disorders remained for most adverse neonatal outcomes, but not for schizophrenia or bipolar disorder. Chapter 6 – Discussion and conclusions. This thesis demonstrates the value of linked population data; has added to the evidence for pregnancy as risk for MBD; provided the first comprehensive prevalence estimates of MBD in pregnancy for all maternities in NSW, including both high and low prevalence MBD; provided evidence to support findings elsewhere of an independent association of alcohol, cannabis, or opiate disorder with poor neonatal outcomes, but not for schizophrenia or bipolar disorder.

  • (2023) Bharat, Chrianna
    Thesis
    Despite strong evidence for the effectiveness of a range of interventions to improve the health and wellbeing of people who are dependent on opioids, morbidity and mortality in this population remains higher than that of the general population. There is a need for innovative approaches to monitor and improve the quality use and safety of available medicines, and to better understand risk factors impacting adverse outcomes in this population. In this thesis, routinely collected administrative data on people with opioid dependence in New South Wales (NSW), Australia, were used to investigate medicine use, including Opioid Agonist Treatment (OAT), opioid analgesics, and other psychotropic medicines. Studies in this thesis examined novel methodological approaches to evaluate medicine exposure and quantify risk, both observed and predicted. This thesis used a diverse range of data sources, including controlled drug registries and pharmaceutical claims databases, linked with health service use and mortality records; and implemented a range of statistical methodologies, including generalised estimating equations, Cox proportional hazards models, and deep learning algorithms. Specifically, this thesis aimed to: (i) estimate retention in OAT and identify person, treatment, and prescriber characteristics that are associated with retention; (ii) develop, evaluate and compare models predicting OAT cessation risk at entry to treatment; (iii) examine trends in opioid analgesic utilisation during periods in and out of OAT; (iv) review methods for generating exposure periods from pharmaceutical dispensing data; and (v) evaluating the all-cause and cause-specific mortality risk associated with opioid analgesics, benzodiazepines, gabapentinoids, and OAT. The first study found retention in OAT to be affected not only by characteristics of the person and their treatment, but also of their prescriber, with longer prescribing tenure associated with increased retention of people in OAT. The results from the second study indicated time-to-event prediction models may be limited in their ability to identify individuals at high cessation risk on entry to OAT. Of the methods used in model development, machine learning approaches performed similarly to traditional statistical methods. In the third study, people with opioid dependence were found to have high rates of recent psychotropic medicine utilisation at the time of opioid analgesic initiation, and reduced opioid analgesic dispensing while engaged in OAT. The fourth study describes a novel method for generating medicine exposure periods from dispensing claims data, developed especially for application to medicines with complex and variable dosing regimens. Finally, in the fifth study, benzodiazepines and gabapentinoids appear to increase mortality risk when used in combination with opioid analgesics, although the risk may be reduced when engaged in OAT. This thesis demonstrates the utility of person-level data linkage and innovative analytical methods to generate real-world evidence about the use and outcomes of prescribed medicines among people with opioid dependence. Awareness of harms in clinical settings and evaluating outcome risk during medicine use would give clinicians the ability to understand who needs prevention and treatment services, ensuring efforts and resources are targeted towards those most at-risk. These represent important strategies for improving quality medicine use and reducing harms among people with opioid dependence.