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ItemThe development, implementation and evaluation of first few X household transmission studies in AustraliaMarcato, Adrian John ( 2023-04)New or re-emerging infectious diseases pose a serious threat to public health. First Few X (FFX) studies provide a platform for the rapid collection of detailed epidemiological data and specimens from cases and their close contacts to understand the potential impact of such diseases. When activated in the early epidemic stages, the data collected from FFX studies can be used to produce estimates of key transmissibility and severity parameters to inform public health and social measures. The Australian Government Department of Health recognise the value of FFX studies, however, detailed protocols in the Australian context were not finalised at the start of my doctoral research in 2019. This thesis documents my experience contributing to the development of a global FFX protocol for pandemic influenza in 2019, as part of my internship at the World Health Organization. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the advent of the global coronavirus disease (COVID-19) pandemic during the first year of my studies rapidly pivoted my PhD focus from piloting a FFX study during the 2020-2021 influenza seasons to implementation in a global health emergency. As such, I detail my role coordinating the design and implementation of the Australian FFX Project for COVID-19 – a national study of confirmed cases of COVID-19 and household contacts conducted between April-October 2020. Using a contact-level mixed-effects logistic regression model, I estimated the household secondary attack rate to be 12% (95%CI 7–17%), which aligned with the estimate produced by my collaborators (15%, 95%CrI 8–25%) using a mathematical model. As this was the first project of its kind in Australia, there were many challenges encountered with respect to logistics, ethics, governance, and data management. I subsequently led a qualitative evaluation of stakeholders involved in the project to consolidate on lessons learnt to inform future FFX platform development in Australia. Four main recommendations were developed from the series of modified Delphi surveys and interviews with key stakeholders, including: forming strong partnerships between health departments and researchers; developing FFX protocols that can be easily adapted for different pathogen contexts; investing in data infrastructure, and; having broad ethical approvals in place before a study begins. The learnings presented in this thesis have significant implications for pandemic planning in Australia, by reinforcing the need for pre-determined and pandemic-ready FFX protocols. The development of a fit-for-purpose FFX protocol in Australia, in advance of the next infectious disease emergency, will enable better understanding of the epidemiology in the early and subsequent epidemic phases of a novel or re-emerging pathogen and help inform a proportionate public health response.
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ItemFactors influencing the development and prognosis of eczemaLopez Peralta, Diego Jose ( 2023-03)Eczema (or atopic dermatitis) is a skin condition characterised by impaired skin barrier function and its chronic and inflammatory nature; it affects children and adults worldwide and considerably impacts their quality of life. Throughout this thesis, I used the term eczema as interchangeable with atopic dermatitis. Eczema is the most frequent skin inflammatory disease in children and adults. Eczema has a wide variation in global prevalence, but it is common in developed and developing countries. Australia is among the countries with the highest prevalence of eczema. The prevalence from 6 to 7 years varied from 0.9% to 22.5%, and from 13 to 14 years, the prevalence ranged from 0.2% to 24.6%. Moreover, it is widely accepted that infants have the highest prevalence rates, which are between 6 and 31%. There are no worldwide estimates of adult prevalence; however, the World Allergy Organization reported a range of 2 to 10%. Eczema is the leading contributor to skin-related disability-adjusted life years or DALYs. The high DALY rate is due to years spent living with a disability. The peak eczema prevalence is during early life, which increases the potential years spent living with this condition. The exact pathogenesis remains unknown; the origin of eczema is most probably due to multiple pathogenic pathways in which there is an interplay between skin inflammation due to skin barrier dysfunction, innate and adaptive immunology, the effect of scratching and environmental factors. There needs to be more information on the environmental factors determining eczema development and its phenotypes, especially in adults. Moreover, eczema has a heterogeneous presentation, which varies in severity, age of onset, and response to treatment. For these reasons, the aims of my doctoral research are to assess(1) the eczema latent classes and their association with risk factors and allergic comorbidities in adulthood, (2) whether the exposure to air pollution is associated with eczema and food allergies in the first ten years of life, (3) whether the association between exposure to air pollution is associated with the incidence and prevalence of atopic and non-atopic eczema in middle-aged adults, (4) the associations between water hardness and eczema symptoms development and (5) the potential associations between occupational exposures and eczema prevalence in middle-aged adults. For the first aim, I used latent class analysis to determine eczema subclasses (Chapter 4). For this research project, I used data from 619 participants from the Melbourne Atopy Cohort Study baseline and all data collection points. There were data collection points from birth to 2 years (every four weeks), from age 3-7 years (yearly surveys), one study at 12 years, another at age 18, and a final one at 25 years. I determined five different eczema subclasses, which had different risk factors and allergic comorbidities. “early-onset persistent”, “early-onset resolving”, “mid-onset persistent”, “mid-onset resolving” and “minimal eczema”. Filaggrin null mutations were associated with the early-onset persistent (OR=2.58 95%CI:1.09-6.08) and mid-onset persistent class (OR=2.58 95%CI:1.32-5.0). Compared with “minimal eczema”, participants from early-onset persistent class had higher odds of eczema (OR=11.8 95%CI:5.20-26.6) and allergic rhinitis (OR=3.13 1.43-6.85) at 18 and at 25 years eczema (OR=9.37 95%CI:3.17-27.65), allergic rhinitis (OR=3.26 95%CI:1.07-9.93) and asthma (OR=2.91 95%CI:1.14-7.43). Likewise, mid-onset persistent class had higher odds of eczema (OR=2.59 95%CI:1.31-5.14), allergic rhinitis (OR=1.70 95%CI:1.00-2.89) and asthma (OR=2.00 95%CI:1.10-3.63) at 18 and at 25 years eczema (OR=6.75 95%CI:3.11-14-65), allergic rhinitis (OR=2.74 95%CI:1.28-5.88) and asthma (OR=2.50 95%CI:1.25-5.00). Allergic and food sensitisation in early life was more common in those in the persistent eczema subclasses. To achieve the second aim, I assessed the association between air pollution associated with eczema and food allergies in the first ten years of life (Chapter 5). The HealthNuts cohort collected data when the participants were 1, 4, 6 and 10 years respectively. The air pollution data was assigned using a satellite-based land-use regression model. Eczema was defined at 1 year by the parent report and at 4, 6 and 10 years using the International Study of Asthma and Allergies in Childhood definition. Food sensitisation was defined using skin prick tests and food allergy using oral food challenges in each wave. A total of 4,668 infants were included in the analyses. NO2 exposure at 4 years was associated with food allergy prevalence at 6 years (aOR:1.63 95%CI:1.00-2.64). A higher concentration of PM2.5 at 1 year was associated with having food allergy at 4 years (aOR:1.39 95%CI:1.07-1.81) per 1.6 microg/m3 PM2.5 increase) and at 6 years (aOR:1.32 95%CI:1.02-1.71) per 1.6 microg/m3 PM2.5 increase). Air pollution exposure at 1 year was associated with persistent food allergy and peanut allergy. In contrast, there was no evidence of associations between air pollution markers and eczema during the same period. To accomplish the third aim, I analysed the effect of ambient air pollution markers on eczema in a cohort of adults (Chapter 6). The study population came from the Tasmanian Longitudinal Health study, and the specific data for this project came from participants of the 2002 and 2012 proband studies. The air pollution data came from satellite-based land-use regression models based on the participants’ home locations. Participants completed a self-administered postal survey and attended a clinic visit. Of 3153 participants in both follow-ups, 2369 had valid skin prick tests. For males, a 2.3 ppb increase in baseline NO2 was associated with increased odds of prevalent eczema (OR=1.15 95%CI:0.98-1.36) and prevalent atopic eczema (OR=1.26 95%CI:1.00-1.59). These associations were not seen in females (P for interaction=0.08, <0.01). For both sexes, a 1.6 microg/m3 increase in PM2.5 exposure at follow-up was associated with increased odds of aeroallergen sensitisation (OR=1.15 95%CI:1.03-1.30). To achieve the fourth aim, I investigated how water hardness is related to eczema in adults (Chapter 7). I used the data from the UK Biobank study; the initial assessment visits were done between 2006 and 2010. Detailed data were collected through a touchscreen questionnaire, a nurse-led interview and the participant’s medical history. In 2014, a subset of participants repeated the baseline assessments and assisted with the imaging visits where similar data was collected. Data on domestic water supply was obtained from local water supply companies in England, Wales, and Scotland. This data was linked to the participants based on their approximate home location. 306,531 participants with a mean age of 57 years nested across 7642 postcodes were included in the baseline analysis, and 31,036 participants nested across 3695 postcodes were included in the follow-up analysis. We observed an increase in the odds of eczema at baseline (OR: 1.02 95%CI 1.01-1.04) per 50 mg/L of CaCO3 increase. Furthermore, exposure to domestic hard water (>200 mg/L of CaCO3) was associated with increased odds of prevalent eczema at baseline (OR: 1.12 95%CI 1.04-1.22). Moreover, there was a significant linear trend (p-value: <.001) in which increasing levels of hard water increased eczema prevalence risk. No association was observed with the incident eczema or eczema at follow-up. The intraclass correlation coefficient for postcode was 1.6% (95%CI:0.7-3.4) and remained unexplained by area-level socioeconomic measures. To realise the fifth aim, I assessed the association between several occupational exposures and eczema using a job exposure matrix (Chapter 8). The data for this study came from 3,609 participants from the 2012 follow-up from The Tasmanian Longitudinal Health study when participants had a mean age of 53. Participants completed a self-administered postal survey that collected sociodemographic characteristics and medical diagnoses and completed the lifetime work history calendar. Cumulative exposure to mould was associated with increased odds of current eczema (adjusted odds ratio (aOR)=1.08 95%CI:1.00-1.18 per 5 years exposure-equivalent). Similarly, current occupational exposure to animals (aOR=2.88 1.34-6.22), storage mites (aOR=2.78 95%CI:1.29-5.99) and endotoxin (aOR=1.96 95%CI:1.05-3.66) were associated with increased risk of current eczema. Furthermore, increased odds of NAE was associated with current exposure to animals (aOR=5.33 95%CI:1.37-20.7), storage mites (aOR=5.39 95%CI:1.39-20.9), and metalworking fluids (aOR=1.11 95%CI:1.01-1.23). Current exposures to isocyanates (aOR=4.65 95%CI:1.04-21.4) and acrylates (aOR=7.44 95%CI:1.38-24.8) was associated with AE. Altogether, the findings of my doctorate work have important public health and research impacts and have reduced the knowledge gaps in this area of research (Chapter 9). I showed that early detection of eczema subclasses might be important as persistence classes were associated with more allergic comorbidities. The identification of eczema subclasses may aid in class-specific preventive or therapeutic strategies. I provided evidence of environmental risk factors for eczema in adults, an area that is lacking research. Increased exposure to air pollution was associated with eczema outcomes in adults. Increasing levels of hard water were related to an increased risk of eczema. Occupational exposures to animals, storage mites, endotoxin, metalworking fluids, isocyanates and acrylates were associated with eczema outcomes in adults. Raising awareness and limiting exposures to these risk factors is likely to aid the reduction of eczema prevalence. Air pollution exposure may be a risk factor for food allergy in infants. Avoidance of air pollution in early life could potentially be a food allergy preventive measure. The strengths of this body of research are (1) the data used for this work came from a large prospective cohort study, (2) the use of well-characterised definitions of allergies and (3) the use of contemporary statistical methods, including multilevel modelling and latent class analysis.
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ItemRegulation in Need of Therapy? Relationships Between Doctors’ Health, Medical Regulation, and Medical Negligence Claims in Australia: A Legal, Quantitative, and Qualitative AnalysisBradfield, Owen Matthew ( 2023-05)Background: Medical regulation and medical negligence litigation provide important mechanisms for maintaining quality and safety in healthcare, by ensuring that medical practitioners (hereafter “doctors”) comply with peer professional standards and codes of conduct. They also provide opportunities for patients who suffer harm resulting from medical care to seek answers, redress, and assurances that mistakes will not be repeated. Therefore, notifications and claims can provide an important window into patient harm. Predicting which doctors are at risk of regulatory notifications or medical negligence claims can help to reduce patient harm before adverse events occur. Despite this, there is growing evidence that regulatory notifications and negligence claims increase a doctor’s risk of developing depression, anxiety, and suicidal ideation. An improved ability to predict and avert regulatory notifications and medical negligence claims may not only reduce patient harm, but may also reduce the adverse consequences for doctors subject to these processes. Indeed, a singular focus by regulators on public protection at the expense of doctors’ interests may paradoxically compromise patient safety. This research aims to provide the first detailed study of the risks, predictors and implications of immediate regulatory action, medical negligence claims, and health impairment allegations against doctors in Australia, with particular attention on the intersection between regulatory and negligence claims and the health and wellbeing of doctors. Methods: This thesis incorporates ten studies, all of which have been published in peer reviewed journals. A mixed methods approach is employed. Publications 1, 2, 6 and 10 adopt traditional doctrinal and comparative legal methods that focus on legal precedent and principles to trace how medical regulators, Courts, and Tribunals in Australia and six other jurisdictions approach regulatory decisions and sanctions (primarily immediate action and health impairment allegations) using publicly accessible legal databases. Publications 3, 4 and 5 adopt a quantitative approach. Publication 3 is a retrospective cohort study of 11,200 health practitioner notifications to Ahpra, in which logistic regression and case-level analyses are used to assess the association between immediate action and practitioner characteristics, notification type, and the use of restrictive final action. Publications 4 and 5 are prospective cohort studies using data from over 12,000 participants in the Medicine in Australia Balancing Employment and Life (MABEL) survey. Logistic and linear regression analyses are used to assess the relationship between medical negligence claims, and vocational and psychosocial variables, correcting for confounding variables. Finally, Publications 7, 8 and 9 employ a qualitative design using a trauma-informed approach to one-on-one in-depth semi-structured interviews with 21 allegedly impaired Australian and New Zealand doctors and four experts in doctors’ health to understand their experiences with regulatory processes. Main Findings: Part I: Australian doctors are vulnerable to the far-reaching implications of untested allegations that can result in immediate action. Compared to overseas jurisdictions, statutory thresholds are lower, the scope is wider, and the limitations on regulatory powers are fewer. Moreover, immediate action does not reliably predict the severity of final disciplinary outcomes. In nearly half of all notifications where immediate action was taken, no final regulatory action was required. Conversely, over 80% of notifications resulting in final regulatory action were not preceded by any immediate action. Part II: High job demands, low self-rated life satisfaction, recent serious personal injury or illness, and working at least full-time in a regional centre increase the risk of doctors being sued. An agreeable personality was protective. Working regionally, having low life satisfaction, and not achieving work-life balance predicted claims in male doctors only, whereas working more than part-time hours and having a recent personal injury or illness predicted medical negligence claims in female doctors only. Increasing age predicted claims more strongly in male doctors. On the other hand, being sued was not associated with changes in self-rated health or self-rated life satisfaction, after controlling for vocational factors. Part III: Compared to New Zealand, Australian Courts and Tribunals are less willing to consider the rehabilitation and return-to-work needs of impaired doctors when determining disciplinary sanctions for alleged health impairment, or when deciding applications to suppress identifiable personal information in published reasons. In qualitative interviews, doctors with mental health and substance use challenges report avoiding treatment for fear of being reported to regulators. Ironically, this is associated with worse perceived health outcomes and harsher regulatory sanctions. Despite recognising that regulatory processes also positively influenced aspects of their health, some allegedly impaired doctors would only seek future treatment anonymously or overseas because distressing experiences of regulatory processes reinforced their initial fears. Allegedly impaired doctors were strongly motivated to participate in my qualitative research for their own benefit (desire to be heard, catharsis, and empowerment) and to benefit others (to change the system, and to avoid other doctors experiencing what they experienced), suggesting that perceived benefits outweigh perceived risks of participating in this sensitive research. Conclusions: This PhD represents a significant contribution to the Australian academic literature examining the intersection between medical regulation, medical negligence litigation and doctors’ health. This work is timely, as it occurs against the backdrop of the COVID-19 pandemic, which has caused significant disruption to health systems, leading to high rates of burnout among doctors, particularly general practitioners, who are leaving the profession. Regulation and litigation exist to protect the public from unsafe, unethical, or poorly performing doctors. However, these systems need to be fit for purpose. While it is disconcerting for the public to learn that a doctor’s ability to safely practise may be adversely affected by a medical condition, overly punitive regulation may indirectly harm the public by discouraging candour, encouraging mistakes to be concealed, and creating fear, anxiety, and avoidance of help-seeking amongst the medical profession. This can worsen health outcomes for doctors. This may ultimately exacerbate, rather than address, the potential risks posed to the public by impaired doctors. The findings of this research will assist doctors, regulators, Tribunals, legal representatives, and medical indemnity insurers to better support doctors who are facing, or at increased risk of, regulatory or negligence complaints. This will not only benefit the doctors concerned, but will also support safer systems of healthcare for the benefit of patients and the wider community, both in Australia and overseas.
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ItemA Cultural Adaptation of the World Health Organization’s Mental Health Gap Intervention Guide for use in Community Healthcare Centres, in Shenzhen, ChinaSearle, Kendall Anne ( 2022-11)Over the last decade, China has instigated substantive national health system reform and established a new primary healthcare sector. Shenzhen, China’s flagship of innovation, rapidly developed a network of Community Healthcare Centres (CHC), doubled its medical workforce and now aspires to provide high quality person-centred care. Newly appointed doctors, however, have received limited mental health training and are insufficiently equipped to identify and manage depression. Against a backdrop of high depression prevalence and limited mental health literacy, most depression cases continue to go undetected and untreated. The World Health Organization’s (WHO) Mental Health Gap Intervention Guide (mhGAP- IG.v2), is a decision-support tool for non-specialists, to support assessment, management and follow-up of priority mental, neurological and substance use disorders, including depressive disorder. mhGAP-IG.v2 offers CHCs an evidence-based training resource, however, it requires adaptation to take account of China’s unique healthcare system and cultural context for mental health services. This PhD study is the first in China to involve primary healthcare in the adaptation of the depression component of mhGAP-IG.v2 for the community healthcare context. Designed as a mixed-methods study, it applies the Theoretical Domains Framework (TDF), innovative mental health workshops and the Delphi approach to: 1) explore the current barriers and enablers to depression care in the CHC setting; 2) to compare the mhGAP-IG.v2 against the current clinical practice; and 3) to elicit consensus among primary care doctors to inform the adaption of mhGAP-IG.v2. This research presents the proposed adaptation of mhGAP-IG.v2 for each step of assessment, management, and follow-up of depression. Proposed adaptations include: modifications of the format and content of symptom listings to reflect the cultural nuances; country-specific healthcare priorities and a life course approach for primary care; restructuring of the management section to better reflect CHC role as a key coordinator of intersectoral care; and full replacement of the follow-up section with action-oriented templates for a mental health treatment plan and follow-up review summary to support patient-centred care. Supplementary charts provide additional guidance for person-centred enquiry, the use of assessment instruments and managing patient information. Family members are incorporated as a vital resource to care. Increased attention to suicidal risk is emphasised throughout. The final form of the adapted depression component of mhGAP-IG.v2 will require further development and input from multiple stakeholders at local and national level.
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ItemDetermining effective and safe treatments for vivax malaria using a modelling and simulation frameworkMehdipour, Parinaz ( 2023-02)Background Malaria is a mosquito-borne disease found in 84 countries. Almost half of the malaria cases in Asia and South America are due to Plasmodium vivax (P. vivax). P. vivax parasites stay dormant in the liver, releasing parasites into the bloodstream weeks to months after the initial infection. Primaquine is the only widely available drug that targets the parasites in the liver, however, the recommended 14-day course of primaquine has low adherence and there is an increased risk of haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. This thesis aims to improve the effectiveness and safety of primaquine regimens for P. vivax by better understanding the effect of adherence on effectiveness through an individual patient data meta-analysis and by using a complex mechanistic within-host model to characterise red blood cell (RBC) dynamics and explore the safety of primaquine regimens for G6PD-deficient individuals. Methods Individual patient data from vivax efficacy studies were pooled to investigate the impact of adherence to primaquine on the risk of P. vivax recurrence between days 7 and 90 after starting treatment. Adherence to primaquine was assessed based on supervision status and the total versus expected mg/kg dose administered. The safety of primaquine dosing schemes was explored through the development of a within-host model that captures the effect of primaquine on RBC production and destruction. The mechanistic RBC model was fitted to haemoglobin and reticulocyte measurements from a regimen-adaptive trial of ascending primaquine doses in G6PD-deficient individuals using a Bayesian hierarchical framework. The posterior distributions of the model parameters were then used to determine safe primaquine dosing strategies for G6PD-deficient individuals. Mechanistic within-host models are valuable tools to determine the safety and efficacy of a drug, guiding the development of optimal treatment regimens. However, there are challenges with parameter estimation of these complex non-linear models. Two Bayesian hierarchical approaches for model fitting and parameter estimation of complex non-linear mechanistic models were assessed using a simulation study of hypothetical patients receiving primaquine. The one-stage method analyses all individual data profiles simultaneously to estimate both the population and individual-level parameters, whereas the two-stage approach fits the within-host model to each individual data profile separately and uses the individual-level parameter estimates as proposal distributions to derive the population-level parameters. Results Individual data from 32 studies involving 6,917 patients treated with primaquine showed that reduced adherence increased the risk of vivax recurrence. The Adjusted Hazard Ratio (AHR) was a 2.3-fold [95% Confidence Interval (CI): 1.8-2.9] to 3.2-fold [95% CI: 1.5-6.7] increase in the rate of recurrence when adherence was poor (<50%), defined by supervision or total mg/kg dose, respectively. Mechanistic modelling of the RBC profiles of 24 subjects from the Primaquine Challenge Study showed that ascending regimens of primaquine resulted in predictable self-limiting haemolysis and should be safer than a single high dose. In particular, the mechanistic model describing the RBC dynamics estimated that high primaquine doses (45 mg base) resulted in a reduction of RBC lifespan of approximately 35%. Simulations from the model determined an optimal dosing regimen of 5 mg/kg over 14 days was safe for individuals with dominant G6PD deficiency variants in Southeast Asia. In a simulation study comparing two estimation methods for fitting mechanistic within-host models to longitudinal data in a Bayesian hierarchical framework, the two-stage approach produced comparable point estimates to the one-stage approach for estimation of parameters of the within-host RBC model and was faster to implement. Conclusions This thesis provides evidence to improve the effectiveness and safety of primaquine radical cure for P. vivax; through the importance of enhanced adherence and the potential reduction of haemolysis in vulnerable G6PD-deficient individuals with a proposed ascending dose regimen. For estimation of computationally prohibitive mechanistic within-host models, the two-stage estimation method may be a suitable alternative.
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ItemThe role of short-term grass pollen exposure in allergic disease and lung healthIdrose, Nur Sabrina ( 2023-02)Background: Australia has one of the highest prevalence of allergic diseases. Although the mortality rate is low, allergic conditions are associated with significant burden. Environmental risk factors of allergic diseases include exposure to aeroallergens such as pollen. In Australia, temperate grass pollen is the primary seasonal aeroallergen. Research Gaps: Although it is well-established that temperate grass pollen can trigger asthma hospitalisations, its relationship with lung function and airway inflammation at a community level is understudied. Furthermore, no study to date has considered the short-term associations between pollen exposure and food allergy. Studies on selective populations have shown that eczema can be exacerbated with increasing ambient pollen exposure, but population-based studies are lacking. Moreover, the evidence on the potential effect modification by individual and environmental factors on the associations is scarce. Aim: I investigated the associations between short-term grass pollen exposure and lung function, airway inflammation, food allergy and eczema across different age groups within the community and identified potential effect modifiers of these associations. Methods: My doctoral research utilised a systematic review methodology and original data from large population-based cohorts: HealthNuts, The Melbourne Atopy Cohort Study (MACS) and the Tasmanian Longitudinal Health Study (TAHS). Grass pollen exposure was assessed either using daily concentrations or the season as a proxy measure of exposure. Where daily pollen data were available, exposure was investigated on the day of exposure (lag 0) and up to three days before (lag 3). Statistical modelling was performed accounting for the distribution of the model residuals, the functional form for the associations between the exposure and outcomes, and confounders. Interactions with individual and environmental factors were explored using likelihood ratio tests. Results: Research Question 1 – The systematic review showed that outdoor pollen exposure is an important risk factor for type-2 inflammation in the upper and lower airways in people with ever asthma and/or seasonal allergic rhinitis, but the evidence on lung function was limited (Chapter 3). Research Question 2 – Increasing grass pollen concentrations were associated with reversible obstructive lung function deficits in children with allergic disease, the greatest risk of exacerbation in food allergic children (Chapter 5). Research Question 3 – There was evidence of a relationship between increasing grass pollen concentrations, and subsequent airway inflammation (1-2 days after the exposure) and lung function deficits (2-3 days after the exposure). Adults and individuals with co-existing allergic diseases were especially vulnerable. (Chapter 6). Research Question 4 – Peak grass pollen season was associated with lower pre- and post-bronchodilator lung function in smokers with allergic respiratory disease, those exposed to higher traffic-related air pollution, with co-existing allergic diseases or with poor adherence to inhaled corticosteroids (Chapter 7). Research Question 5 – Persistent grass pollen exposure over 4 days was associated with increased odds of food skin-prick test reactivity and eczema flares in children, but the impact was greater if peanut allergy was already present (Chapter 8). Conclusions: My work has significant public health and clinical implications. Notably, there was evidence of association between ambient grass pollen exposure, and subsequent lung function impairment and airway inflammation in both children and adults, mainly on the large and medium-small sized airways. There was also an association with post-bronchodilator measures in middle-aged adults, implying that the pathology in this age group may be distinct from classic, reversible asthma. Furthermore, the negative health impacts of short-term grass pollen exposure may extend to non-respiratory allergic diseases such as food allergy and eczema. Lastly, I identified high-risk groups who were more vulnerable to grass pollen, which were adults, smokers with allergic respiratory disease, those exposed to higher traffic-related air pollution, with allergic co-morbidities or with poor adherence to inhaled corticosteroids.
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ItemParadoxes of collective drinking: The role and meaning of air kata-kata among young people in Jayapura and Sentani, Papua, IndonesiaPertiwi, Ratih Eka ( 2023-02)This thesis explains the role and meaning of alcohol consumption among young people in Jayapura and Sentani, two sites in Papua, a resource-rich Indonesian province on New Guinea Island. In describing the youths’ experience with alcohol, this study critically engages with previous studies focusing on alcohol globally as well as with theories from health and anthropological studies specific to Papua. Based on 24 months of fieldwork conducted with young people from Jayapura and Sentani, I investigate the youths’ drinking patterns, the benefits and costs of their alcohol use and how the social, cultural and political contexts in which they live interact with their drinking practices. This includes examining the wider societal expectations by gender that there might be for drinking among young people. Findings from this study show that the wider Indonesian society has negative stereotypes towards Papuan youths and their drinking behaviours. This ethnography, therefore, provides a valuable anthropological perspective by offering emic insights that balance the negative stereotypes exhibited towards Papuan youths and their drinking behaviours that have saturated the consciousness of wider Indonesian society. In this study, I have provided the voices of the youths to counteract the outraged concerns of the general community. This study’s findings also demonstrate how racism and marginalisation are central to the experiences of the youths, especially to young Indigenous Papuans, when viewed through the politics of alcohol—a perspective that is greatly overlooked in the literature focusing on Indigenous Papuan youths. This study reveals and focuses on three paradoxes regarding young people’s drinking practices, and how these inconsistencies are handled at various social levels. At the state level, controls over alcohol in Papua are being proposed, aimed to protect Papuan people. However, the same rules and controls are utilised to profit and take further advantage of Papuans. Findings regarding gendered practice of drinking show how the state articulates what it means to be a good Indonesian woman, but Papuan women have been viewed differently and discriminated against. At an individual level, drinking sessions are viewed as a space where the youth can express themselves, but on the other side are a source of violence and ill-health. At the regional level, the Governor of Papua stated that alcohol contributes to the death of Papuans. However, almost nothing has been done to reduce alcohol-related harms among young Papuans. In this powerless situation, the youths’ drinking groups become more than an act of friendship; they provide a space for the youths to support each other and, to some extent, improve their lives. This thesis’ findings include examples of young people who attempted to change the harmful patterns of drinking in their drinking groups. This includes young people who protested against alcohol sales in Sentani, which resulted in a change in alcohol regulation. Finally, this thesis also includes a case study of a group of youths in Jayapura who established a youth organisation to provide alcohol education for their peers and to reduce alcohol-related harms among the young people in their area.
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ItemAssessment of the completeness of death registration and estimation of national and subnational mortality in NepalPandey, Surender Prasad ( 2022)Introduction Timely and quality mortality data provide important evidence to inform health policy and monitor the progress of local and national development goals. In Nepal, a civil registration and vital statistics (CRVS) system has operated for several decades. However, the system’s focus has been on legal and administrative aspects and no vital statistics have been produced from its data. Censuses and surveys collect mortality data, but they focus on early age mortality while adult mortality data suffer from quality and completeness issues. There is hence limited information about mortality in Nepal and reliance on model-based estimates provided by the Global Burden of Disease (GBD) Study and the United Nations (UN). This thesis aims to fill this knowledge gap in Nepal by assessing the completeness and quality of national mortality data sources, estimating the key national and subnational mortality indicators, assessing differentials in death registration completeness by socio-economic, demographic, and geographical characteristics and identifying the main barriers and enablers for death registration. Methods The empirical completeness method was used to measure the completeness of offline (paper-based) and online death registration and household deaths reported in the CRVS Survey 2015/16 by sex, province and ecological belt. The empirical completeness method estimates the completeness of death registration or reporting using data inputs of the registered crude death rate, under-five mortality rate, and the percentage of the population aged 65 years and above. These results together with a linear regression analysis of estimated true crude death rates and the empirical completeness method extension were used to estimate adult mortality and life expectancy at birth by sex, province, and ecological belt in 2017. The CRVS Survey 2015/16 was analysed using bivariate and logistic regression to assess characteristics that predict the likelihood of death registration. The nationally representative CRVS Survey was conducted in 2015 and 2016 and collected information about deaths reported to have occurred in the preceding three years (2013-2015). Responses to this survey from households and service providers (local registrars) were examined to identify reasons for registration and non-registration of deaths, and ways to make death registration more convenient. Results The completeness of the offline death registration in Nepal was 69% in 2017 and had not increased since 2013. Completeness was higher for males (73%) than females (65%) and provincially it ranged from 90% in Gandaki to 39% in Karnali. The completeness of online death registration was 32% in 2019 and completeness of death reporting in the CRVS Survey was 75% in 2015 but just 54% in 2014. Adult mortality in Nepal in 2017 was estimated to be 159 deaths per 1000 population for males and 116 for females and varied by ecological belt (males: Terai 148 to Mountain 181; females: Hill 101 to Mountain 140) and province (males: Madhesh 129 to Karnali 224; females: Bagmati 92 to Sudurpashchim 159). Life expectancy at birth in Nepal was estimated 69.7 years for males and 73.9 years for females in 2017, being marginally higher than GBD estimates and higher than UN estimates. It also varied by ecological belt (male: Mountain 67.3 to Hill and Terai 70.3; female: Mountain 70.9 to Hill 75.6) and province (male: Karnali 64.9 to Madhesh 71.8; female: Sudurpashchim 69.6 to Province 1 77.0). Estimated subnational mortality indicators had a strong correlation with monetary poverty levels. CRVS Survey results showed that there was less likelihood of the registration of the deaths occurring in early age, in households with illiterate heads and in households with fewer communication facilities. The main reasons for registering a death according to households were for property entitlement transfer, social security access and other legal purposes (85% combined). Most deaths (70%) had not been registered by households because they believed they did not have to register them. Both households and service providers believed that organising mobile registration camps and promoting online registration and registration from the place of occurrence as ways to enable greater death registration in Nepal. Conclusion Each mortality data source in Nepal, including CRVS, has weaknesses in terms of completeness and quality. Subnational mortality indicators vary significantly, and these differences are plausible when compared with poverty levels. The differentials, barriers and enablers of death registration according to the CRVS Survey provide important evidence for the design of interventions to help Nepal achieve complete death registration. In particular, the continued roll-out of the online registration system will be important for Nepal to have a major source of timely and reliable mortality data in the future.
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ItemPreventing violence-related death and morbidity among people who have had contact with the criminal justice systemWilloughby, Melissa ( 2022)Although rates of violence globally have been decreasing in recent decades, the risk of experiencing violence remains disproportionally concentrated among people who experience marginalisation and disadvantage. Many of the health and social inequities that predispose people to experiencing violence are highly prevalent among those who have had contact with the criminal justice system. However, there is little evidence on the risk of violence victimisation in this population. This constrains our ability to design effective violence prevention strategies that can meet and respond to the needs of those who have had contact with the criminal justice system. My thesis aimed to fill this gap in the literature by generating novel evidence on the epidemiology of violence-related death and morbidity among young people and adults who have had contact with the criminal justice system. I conducted a narrative review of the literature, five discrete original research studies, and I produced a protocol for a systematic review and meta-analysis, and a letter to the Editor. I also extended the Public Health Approach to Violence by applying it, for the first time, to those who have had contact with the criminal justice system. My thesis findings indicate that young people and adults who have had contact with the criminal justice system have a risk of violence-related death and morbidity that is far greater than that of the general population. Among people who have had contact with the criminal justice system, women, Indigenous people, and those with mental health and/or substance use issues are particularly at risk. Evidence-informed violence prevention strategies are urgently needed in this population. The findings of my thesis can be used to inform the development of such strategies. Taken together, the evidence suggests that in order to be effective, a violence prevention approach for this population should address the health and social inequities that are both drivers of violence and disproportionately impact people who have had contact with the criminal justice system. Effective responses must also take into consideration the sex- and culturally-specific needs of those who have had contact with the criminal justice system. Until such action is taken, people who have contact with the criminal justice system will continue to experience violence victimisation at a rate that far exceeds that in the general population.
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Item“It’s a space for us to express our rights, to change ourselves and our community”: A feminist ethnographic study of Syrian refugee women’s experiences in and because of participating in a women and girl safe space in Beqaa valley, LebanonNasr, Hala ( 2022)Women and girl safe space interventions are increasingly being implemented by multilateral agencies and, international and local non-governmental organisations (NGOs) in areas affected by forced displacement, disaster, and conflict interventions. Women and girl safe space interventions employ gender-segregated space and collective-based strategies in the pursuit of women’s empowerment. There is little research supporting the effectiveness of women and girl safe spaces in empowering women. Much of the existing research uses quantitative methods, and sheds little light on what actually happens in women and girl safe spaces, or the nature of women’s experiences participating in them. To address this, I conducted a feminist ethnographic study exploring Syrian refugee women’s experiences in and because of participating in a women and girl safe space in the Beqaa valley, Lebanon. My research sought to answer the questions: What were women’s experiences in and because of participating in the women and girl safe space? What power relations, practices, and structures facilitated these experiences? What role did their participation (if any) play in transforming gendered norms and power relations? Following the introduction chapter, I begin with an overview of the relevant literature, where I situate women and girl safe spaces implemented by development and humanitarian organisations as one type of ‘safe space’ and explore the current evidence on their effectiveness for empowering women. Using The Roestone Collective’s (2014) ‘safety from/safety for’ conceptual framework, I also explore the common threads across the design and implementation of women and girl safe spaces, linking these threads to the feminist development scholarship on collective empowerment. I then describe my research context in Beqaa, Lebanon. I introduce the intersecting histories of Lebanon and Syria and the 2011 Syrian conflict that led to the mass forced displacement of Syrians, followed by a description of the women and girl safe space where my research took place. I then present the transnational feminist methodological approach I took to my research, including my positionality, data collection methods and analysis, ethical considerations, and strengths and limitations of my study. Given my thesis-with-publication approach, I present my research findings in journal articles. The first journal article (Chapter 4) focuses on the empowering effects of participation in the women and girl safe space on Syrian women and the various safety-making practices and structures that facilitated those empowering effects. The second journal article (Chapter 5) focuses on complicating three dominant assumptions operating in the women and girl safe space – that Syrian women share a common identity; that women are allies and supportive of each other; and that women’s relationships are governed by non-hierarchical power relations – through vignettes that highlight differences, hierarchies, and conflict between women. The final journal article (Chapter 6) highlights the unintended negative consequences when meanings attached to empowerment were imposed by the organisation or not shared amongst women, putting forth several provocations for development and humanitarian practice. In the final chapter, I summarise the key findings across my research, which suggested there were empowering effects for women who participated in the women and girl safe spaces. I then bring together the different threads of the arguments I make across my individual findings chapters. I ultimately advocate for development and humanitarian organisations to embrace a collective self-determination approach, where women participating in women and girl safe spaces are empowered to develop its mandate actively and collectively over time. I also emphasise the importance of fostering ‘enabling’ relationships between participating women (and between participating women and staff), by recognising differences and responding proactively to disempowering or harmful dynamics. I then describe the contributions my research makes, strengths and limitations as well as future research questions, before ending with a final reflection.