College of Medicine and Health - Doctoral Theses
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Item An evaluation of Ireland’s water fluoridation policy(University College Cork, 2024) Cronin, Jodi; Woods, Noel; Harding, Mairead; Moore, Stephen; Whelton, HelenIntroduction Community water fluoridation (CWF), the controlled addition of fluoride to the water supply, is an approved preventive oral health intervention to reduce the prevalence and severity of dental caries (dental decay). Celebrated for its role in reducing dental caries, it is recognised as one of the ten great public health promotion measures of the 20th century. Today, 60 years since fluoride was first added to the public water supply in Dublin, 71% of the Irish population have access to fluoridated water, emphasising the lasting influence of CWF as a fundamental aspect of public health in Ireland. This thesis aims to comprehensively assess the economic and oral health implications of Ireland’s CWF policy within the context of the nation’s hybrid oral healthcare system. This system, operating in parallel to the main healthcare system, combines public and private service provision, with most individuals paying out-of-pocket fees to independent dental practitioners. Methods The thesis explores historical, contextual, and methodological landscapes to provide a comprehensive understanding of the Ireland’s CWF policy and its implications for public health policy. To address the gaps in the evidence relating to CWF in the Irish setting, three studies were undertaken. The first study described in Chapter 6, critically appraises the methodological conduct and reporting quality of economic evaluations (EEs) of CWF. Guided by established principles for reviewing economic evidence, the study assesses the economic evidence using reliable quality appraisal instruments, specifically the Consensus on Health Economic Criteria list (CHEC) and the Consolidated Health Economic Evaluation Reporting Standards statement (CHEERS). Chapter 7, presents an economic evaluation of CWF for schoolchildren, the first formal assessment of its cost-effectiveness in the Irish setting since the adoption of the policy in 1964. Following traditional economic evaluation methods and using epidemiological data from a representative sample of schoolchildren with and without lifetime exposure to CWF, a cost-effectiveness analysis (CEA) is performed from the health-payer perspective. The third study, presented in Chapter 8, examines the long-term effects of exposure to the Ireland’s CWF policy on dental caries among adults. The study uses epidemiological, demographic, and sociological data from adult residents of the Republic of Ireland (Ireland) with lifelong exposure to a CWF policy and adults in Northern Ireland without exposure to CWF. Negative binomial regressions are employed to estimate the relative risks of various explanatory variables, including CWF exposure, on dental caries experience among adults. Results Collectively, the results of these three studies provide a more comprehensive understanding of the effects of Ireland’s CWF policy on oral health outcomes. Chapter 6, highlights persistent misunderstandings in valuing consequences within cost-benefit analyses of CWF. The study also identifies shortcomings in the measurement and valuation of costs and outcomes across all evaluation types. Moreover, it reveals methodological subtleties that may not be discerned by the quality assessment instruments, such as accurately estimating the impact of fluoridation and the inclusion of treatment savings within cost estimates. This chapter provides valuable insights into the existing economic evidence of CWF, helping policymakers effectively leverage it to inform resource allocation decisions. Additionally, it may serve as a resource for researchers, facilitating improvements in the methodological rigor and reporting standards of future EEs of CWF. In Chapter 7, compelling economic evidence highlights the imperative of maintaining public provision of CWF for schoolchildren despite the current environment of multiple fluoride sources. CWF as a health intervention provides a reduction in the national disease burden and offers cost-savings to the health-payer, which in Ireland, is often the private individual. The findings presented by the analysis in Chapter 8, reveals that adults, exposed to a CWF policy for most of their lives, show a significantly reduced dental caries experience compared to individuals of similar age with no exposure. Furthermore, exposure to the CWF policy emerges as the most influential variable affecting caries outcomes when compared to the other variables examined in the study. Conclusions The mandatory legislation surrounding CWF in the Irish context has been instrumental in ensuring widespread access to the benefits of this preventive measure. The findings of this thesis affirm that Ireland’s CWF policy has not only been the cornerstone of its preventive oral healthcare strategy but also a steadfast pillar of the publicly funded oral healthcare service. Despite the challenges posed by a fragmented and underfunded oral healthcare system that has yet to be fully integrated into the broader healthcare agenda, the CWF policy has reliably maintained the population’s oral health since its introduction in 1964. This highlights the policy’s critical role in mitigating the negative impacts of systemic shortcomings while also demonstrating its capacity to drive enhancements in oral health outcomes for all members of the community. By providing a consistent and accessible source of fluoride through the public water supply (PWS), CWF offers a cost-effective and broad-reaching intervention to improve oral health outcomes. The findings of this thesis emphasise the significance of CWF as a public health measure in reducing the prevalence of dental caries and health inequalities, supporting its continued implementation as a public health strategy.Item Caries and developmental defect of enamel prevalence in adults with cystic fibrosis(University College Cork, 2024) O'Leary, Fiona; Hayes, Martina; Burke, Francis M.; Roberts, Anthony; Health Research Board; Cystic Fibrosis IrelandObjectives This research had five objectives. 1. To evaluate the available literature regarding oral disease in people with cystic fibrosis specifically caries and developmental defects of enamel. 2. To ascertain the current practices and attitudes of dental practitioners regarding the provision of oral care for people with cystic fibrosis. 3. To ascertain the current practices and attitudes of dental practitioners regarding the provision of dental treatment pre and post solid organ transplantation. 4. To assess a cohort of people with cystic fibrosis for the presence of developmental defects of enamel and compare the results with a control group of people without cystic fibrosis. 5. To measure caries experience in a cohort of people with cystic fibrosis and compare the results with a control group of people without cystic fibrosis. Methods Objective 1 A systematic review of the available literature was conducted for caries experience in people with cystic fibrosis. A second systematic review was conducted assessing the prevalence of developmental defects of enamel in people with cystic fibrosis. Objective 2 & 3 A questionnaire was developed following PPI (patient and public involvement) with representatives of the dental profession and patient advocates from Cystic Fibrosis Ireland. The questionnaire consisted of 56 questions and multiple-choice questions related to cystic fibrosis manifestations and management, dental health certification for solid organ transplantation, and the dental management of people with cystic fibrosis and recipients of solid organ transplants. Dentists were invited to complete the anonymised survey online. Data was collected from 135 dental practitioners. Data was qualitatively analysed. Objective 4 & 5 A total of 92 people with cystic fibrosis and 92 people without cystic fibrosis were recruited for this cross-sectional study. Each participant completed the World Health Organisation's ‘Oral Health Questionnaire for Adults’. Individuals with cystic fibrosis in the study group completed additional questions specifically related to cystic fibrosis diagnosis, treatment and management. All participants underwent an oral examination, performed by two calibrated examiners to assess for the presence of developmental defects of enamel (DDE index), to measure caries experience (DMF) and other clinical variables (periodontal assessment using the CPI-modified index, and oral hygiene status using the Greene–Vermillion index). Collected data was statistically analysed with help from statisticians from the Cystic Fibrosis Registry of Ireland. Results Objectives 1 Studies included in the systematic review demonstrated a trend that caries levels in paediatric populations with cystic fibrosis are lower when compared to a population without cystic fibrosis. Caries levels are higher in adults with cystic fibrosis when compared to populations without cystic fibrosis. Similarly, the majority of included studies indicate that people with cystic fibrosis have a higher prevalence of developmental defects of enamel. Objective 2 & 3 Twenty-four percent (n=32) of dental practitioners were currently providing care for people with cystic fibrosis, 13% (n = 17) did not know, and 63% (n = 85) were not currently providing care for this population. 72% (n = 97) of respondents reported that they were comfortable treating people with cystic fibrosis, 28% (n = 38) said that they were not comfortable treating these patients. Thirty four percent of respondents currently or had previously provided care for recipients of solid organ transplants. 29% (n=36) of dentists had provided dental health certification for individuals undergoing transplantation, only 11% (n=4) had received correspondence or guidance from the patient’s medical team. 88% of respondents consider the currently available literature providing guidance for the provision of dental health certification inadequate. Objective 4 & 5 Sixty-four percent (n=59) of people with cystic fibrosis had developmental defects of enamel, compared to 30% (n=28) of people without cystic fibrosis. The median number of teeth affected by enamel defects in the study group was 1.5, compared to 0 in the control group. The percentage of people with cystic fibrosis with untreated dental caries present was 38% (n=35) compared to 13% (n=12) of people in the control group. The mean DMFT values were higher in the study group compared to the control group but only the decayed value (DT) was statistically significantly higher (0.99 vs. 0.18; (p= <0.001)). Conclusions Objective 1 While there is not a unanimous agreement across all studies, there is a consistent pattern that the prevalence of enamel defects is higher in people with cystic fibrosis compared to individuals without cystic fibrosis. While a pattern emerged that children with cystic fibrosis had lower levels of dental caries compared to healthy children, adults with cystic fibrosis had higher levels of caries compared to adults without cystic fibrosis. Objective 2 & 3 The results from the survey indicate a wide variety in the knowledge, attitudes and practices of dental practitioners regarding the oral health of people with cystic fibrosis. Similarly, the data indicates a wide variation in the provision of treatment for patients undergoing or in receipt of a solid organ transplant. There are currently no guidelines for the provision of dental treatment for people with cystic fibrosis or people pre/post solid organ transplantation. Future research should focus on the development of such guidelines to aid dental practitioners and ensure that patients receive an appropriate standard of care. Objective 4 & 5 In this study the cohort of adults with cystic fibrosis had a higher DMFT when compared to a control population without cystic fibrosis. Adults with cystic fibrosis had a statistically higher prevalence of developmental defects of enamel compared to the control group.Item Bi-directional tumour-host interaction in a murine model(University College Cork, 2001) O'Brien, Mike; Shanahan, FergusTumours evoke immunologic responses yet they continue to grow and develop. The majority of people who develop tumours are immunocompetant, evoke immune responses and yet metastases occur in lymphnodes, potentially the most hostile immune environment. This is the paradox that we are attempting to unravel. It is hoped that this work would eventually lead to improved immunotherapeutic strategies. The primary objective of the work was to study the mechanisms by which tumours of differing origins and antigenic spectra circumvent the anti-tumour immune response to grow and develop. Responses were characterised for two histologically distinct murine tumours grown in immunocompetant, syngeneic mice. Immunological response profiles were defined in terms of lymphocyte proliferation, cytotoxic function and lymphocyte subsets in naive non-tumour bearing mice and mice with increasing tumour burden. The effect of this antitumour immune response on the developing tumour was examined in a model of mixed tumour antigenicity established in our laboratory. The influence of tumour derived immunosuppressive factors on the immune response was examined. These factors were partially characterised and compared to determine if the differing response profiles could be attributed to differing immunosuppressive factors. The possible effect of tumour antigens shed into and processed by the gut associated lymphoid tissue with consequent down regulation of the systemic immune response (Oral Tolerance) to a developing tumour was examined.Item Real-world Orkambi Cork (ROCK) study - a prospective 12 months analysis addressing the impact of CFTR modulation in patients with cystic fibrosis homozygous for F508del CFTR variant(University College Cork, 2024) Arooj, Parniya; Plant, Barry; Eustace, JoeCystic fibrosis (CF) stands as one of modern medicine's success stories, with significant and sustained improvements in survival rates, transforming it from a childhood fatal condition to one of adult survival. Historically, CF management has centered on addressing the consequences of CFTR dysfunction. The introduction of Lumacaftor-Ivacaftor marks a pivotal shift, allowing researchers to assess the impact of CFTR function restoration on both pulmonary disease and extrapulmonary manifestations. Globally, approximately 82% of individuals with CF are homozygous for the F508del mutation, whereas this prevalence is 53% at the Cork CF centre. This study examines the effects of CFTR modulation on clinical outcomes, patient-reported measures, systemic and airway inflammation, and lung microbiota composition.Item AI-based analysis of cerebral oxygenation in preterm and term infants(University College Cork, 2024) Ashoori, Minoo; McDonald, Fiona; O'Halloran, Ken; Science Foundation IrelandPreterm and term infants are vulnerable to brain injuries resulting from inadequate cerebral oxygenation, posing significant risks to their long-term neurodevelopment. Near-infrared spectroscopy (NIRS) is a non-invasive technology capable of monitoring regional cerebral oxygen saturation (rcSO2) and detecting cerebral desaturation events in neonates. However, the clinical utility of NIRS signals remains limited due to challenges in interpreting complex patterns. This thesis aimed to enhance the diagnostic and prognostic value of NIRS by employing advanced signal processing and artificial intelligence (AI) techniques. We developed and optimized methods to extract prolonged relative desaturations (PRDs) from NIRS signals and combined these with machine learning (ML) and deep learning approaches. These models integrated quantitative features derived from rcSO2 and peripheral oxygen saturation (SpO2) signals to predict brain injuries, such as intraventricular hemorrhage (IVH) in preterm infants and hypoxic-ischemic encephalopathy (HIE) in term infants. Our findings demonstrated that features extracted from PRDs significantly outperformed traditional threshold-based approaches in predicting adverse outcomes, achieving an area under the receiver operating characteristic curve (AUC) of 0.846 for IVH detection in preterm infants. Additionally, machine learning models revealed a significant association between rcSO2 patterns and adverse outcomed assessed by MRI, with AUC values reaching 0.73. Deep learning methods further automated feature extraction, providing modest accuracy in detecting MRI-confirmed brain injuries. These results highlight the potential of integrating NIRS with AI-driven analysis to improve early detection and management of neonatal brain injuries. This research lays the foundation for more personalized and timely interventions, ultimately advancing neonatal care and outcomes.