College of Medicine and Health - Doctoral Theses
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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.Item The potential impact of atrial fibrillation screening in Ireland(University College Cork, 2023) Callanan, Aileen; Buckley, Claire; Bradley, Colin; Kearney, Patricia M.; Quinlan, Diarmuid; Health Service ExecutiveBackground Atrial fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia globally (1-4)and is a major risk factor for ischaemic stroke (5, 6), with stroke risk increasing five-fold in the presence of AF (6). However, AF is frequently asymptomatic, and this coupled with its intermittent nature, makes diagnosis difficult (5). If identified, treatment is available which reduces stroke risk by up to two thirds (7, 8). The two primary treatment options for AF are electrical cardioversion or cardioversion with anti-arrhythmic medication or rate control drugs (9). Guidelines also recommend the use of OAC based on individual thromboembolic risk (9, 10). AF screening meets many of the World Health Organisation (WHO) criteria for screening (11) and is recommended nationally (12) and internationally (2). However, to date there is no national screening programme for AF in Ireland. A community setting such as general practice has been identified as a potential location to conduct AF screening and mobile ECG devices have been reported as the preferred screening tools (13). In Ireland, opportunistic AF case finding via pulse palpation was introduced as part of a new chronic disease management programme in January 2020 to a proportion of the population ≥ 75 years, it is available to those who are covered under the national health insurance scheme (14). Studies have reported increased morbidity and mortality associated with AF related stroke compared to non-AF related stroke (1, 15). Previously, there are no robust estimates of the burden (disability and death) associated with AF related stroke and non-AF related stroke in Ireland. This thesis (i) estimates the burden (disability and death) of AF and non-AF related strokes in the Irish context, (ii) identifies facilitators and barriers to AF screening from the perspectives of general practitioners (GPs) in primary care, and (ii) quantifies the yield and feasibility of a pilot AF screening programme in primary care in the south of Ireland. Aims The overall aim of this thesis was to explore the feasibility of opportunistic AF screening in primary care in Ireland with one-lead ECG technology. Specific aim 1: to estimate the burden of AF by investigating the association between AF related and non-AF related stroke with severe stroke outcomes and death in Ireland. Specific aim 2: to identify facilitators and barriers to AF screening in primary care in Ireland from the perspectives of GPs. Specific aim 3: to implement a pilot AF screening programme in primary care in Ireland using one-lead ECG technology. Methods A multiphase mixed method design including quantitative research conducted concurrently with an exploratory sequential design was adopted for this thesis. Three studies were conducted during the three-year research period: • Study 1 – a secondary data analysis of the Irish National Audit of Stroke (INAS). • Study 2 –a qualitative descriptive study of GPs in primary care. • Study 3 – a pilot AF screening programme in primary care in the south of Ireland. The secondary data analysis of the Irish National Audit of Stroke provides robust evidence regarding the burden of AF related stroke in Ireland and highlights the need for further stroke prevention efforts based on the magnitude of morbidity and mortality associated with AF related stroke. Data from the qualitative study was used to inform the pilot AF screening programme. Facilitators and barriers which were identified in this study were incorporated into the design of the pilot AF screening programme. The pilot AF screening study provides real world evidence regarding the implementation of an AF screening programme using one-lead ECG technology. Data from INAS were analysed using Stata SE version 17.0 statistical package. The modified Rankin scale (mRS) was used as a measure of disability. Students t-test was used to analyse difference in numeric variables, displayed as mean, minimum, maximum, range and standard deviation, Chi-square tests were used to analyse categorical variables, reported as numbers and proportions. Logistic regression was used to investigate the association between AF related stroke and non-AF related stroke, disability and death. Study 2 was a qualitative descriptive study of GPs in primary care to identify facilitators and barriers to AF screening from their perspectives. A total of 58 GPs were invited from the north Cork region to participate in individual interviews at their practices, rural and urban, with a view to recruiting a sample of up to 12 GPs. The interviews were audio-recorded, transcribed verbatim and analysed using framework analysis. Study 3 was a pilot AF screening programme in primary care in the south of Ireland using a one-lead ECG device, KardiaMobile. General practitioners (GPs) were recruited from Cork and Kerry and invited patients ≥65 years to undergo a stroke prevention initiative compromising AF screening, blood pressure check and identification of smoking status. Descriptive statistics were carried out using Stata SE 17.0 statistical package. Results Quantitative study; the association between AF related stroke and stroke severity, disability and death. During the three-year study period, 10,528 ischaemic strokes were recorded by INAS, 4489 (43%) were female with a mean age of 74 (SD 13) years. AF related strokes were found to account for approximately 31% of ischaemic strokes. Patients with AF related stroke were on average older 78 (SD 9.9) than those without AF 70 (SD14), (p<0.001) and a higher proportion were females 1433 (45%) (p 0.008). Having a severe stroke (modified Rankin scale measuring disability) was more likely in the AF related stroke group in the univariate model, OR 2.1 (1.9-2.3, p<0.001), and the multivariate model including sex, age, social position (using GMS national health insurance cover as a proxy), marital status and admission to a stroke unit, OR 1.4 (1.3-1.6, p<0.001). The association remained in sensitivity analyses and subgroup analyses providing robust estimates. The increased risk of morbidity and mortality in this study demonstrates the additional burden of AF related stroke and the potential importance of AF screening to identify unknown AF cases who can be assessed for treatment. Qualitative study; identification of facilitators and barriers to AF screening: Eight GPs, four male, four female from five practices participated. Five were from urban practices, three were from rural practices. Facilitators and barriers were sub-categorised into patient facilitators, practice facilitators, GP facilitators, patient barriers, practice barriers, GP barriers, attitudes to AF screening, willingness to facilitate and priority ranking. All eight participants expressed a willingness to engage in AF screening. Time constraints was the barrier discussed most frequently by all participants along with the need for additional staff. Programme structure was the most discussed facilitator by all participants and patient awareness campaigns. These findings were incorporated into the pilot AF screening programme. Cognisant to lack of time identified as a barrier to AF screening, the pilot screening programme used (i) 1-lead ECG device due to its ability to provide an ECG reading in 30 seconds and (ii) a short one-page clinical report form was used for the study to facilitate prompt data collection by participating GPs. Lack of clear onward referral pathways were also identified as a barrier. Thus, a detailed standard operating procedure (SOP) providing guidance on referral to secondary care was provided in the pilot screening programme. The qualitative study identified important data on facilitators and barriers that may be experienced implementing an AF screening programme in primary care and these findings were integrated into the pilot AF screening programme. Pilot AF screening study; implementation of a pilot AF screening programme in primary care in Ireland: The pilot programme was offered to over 400 GP practices. Anonymised data from 3555 eligible patients, across 34 practices (52GPs) was analysed. Of those 1720 (48%) were female, 1698 (48%) were male. The result of the screening intervention, using Kardia Mobile, was 3282 (92%) had normal readings, 101 (3%) had possible AF, 124 (4%) had unreadable or unclassified readings and 48 (1%) missing data. Of the 101 patients who had a possible AF reading, 45 (45%) had AF confirmed as per 12 lead ECG. Uptake from participants was high from both GPs and patients and the yield of the screening was 1.3%. Levels of hypertension were also high in the screened population, and it may be beneficial to incorporate AF screening into an overall stroke prevention programme focusing on a selection of the main cardiovascular risk factors including hypertension. Conclusion AF related stroke accounts for 31% of ischaemic strokes in Ireland and is associated with considerable disability and death. One third of AF related ischaemic stroke patients were diagnosed with AF on presentation with stroke. While a large proportion of those with AF are on OAC, approximately 80%, the findings demonstrate the potential need for screening. The secondary data analysis study identified high levels of morbidity and mortality associated with AF related stroke. This is a significant public health issue. Despite barriers to AF screening identified by GPs in the qualitative study, there was significant willingness to engage in the pilot AF screening programme as demonstrated by high uptake by GPs and patients. Early detection of AF in asymptomatic individuals enabled assessment for treatment. The high levels of high systolic BP detected are notable. It may be beneficial to conduct more comprehensive stroke risk assessments rather than AF screening in isolation.