Medicine - Doctoral Theses

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    Recently qualified doctors learning about end of life care: a socio-cultural perspective
    (University College Cork, 2022) Sweeney, Catherine; Bennett, Deirdre; O'Brien, Tony; National Institute of Allergy and Infectious Diseases
    Background Death and dying are problematic areas in healthcare. In the developed world, socioeconomic and healthcare changes have resulted in increased life expectancy and excessive use of interventions and healthcare resources at the end of life (EoL). Associated with these transformations, there is a wider cultural reluctance to accept the inevitability of death. In the world of contemporary medicine, death can be viewed as failure. Providing care for people approaching and at the EoL is the responsibility of all doctors, not just the remit of a select minority in particular specialties. In the face of increasing specialisation in medicine, generalist competencies can be subverted. Previous research has focused on knowledge, preparedness, and experiences of medical students and recently qualified doctors (RQDs) in palliative and EoL care. Many studies have identified significant deficits and call for inclusion of more content in both formal and informal curricula. Workplace learning about EoL care has not been as well explored from a socio-cultural perspective. The primary aim of this thesis was to explore and offer insights into how workplace socio-cultural factors influence RQD learning and development of capability in EoL care. My research questions were: 1. What and how do recently qualified doctors learn within their physician teams about EoL care? 2. How do recently qualified doctors navigate the wider landscape of practice when caring for patients at the EoL?   3. How do consultants support recently qualified doctors and medical student workplace learning about EoL care? 4. How do specialist palliative care consult team (SPCCT) members perceive RQDs’ capability and involvement in the provision of EoL care? 5. How can specialist palliative care consult team members support recently qualified doctors to develop capability in EoL care? Methodology I have used a qualitative approach in my programme of research. I adopted a socio-cultural perspective, using the theoretical lenses of Communities of Practice (CoP) and Landscapes of Practice (LoP) for analysis. My research was underpinned by an interpretivist paradigm. Methods I conducted 4 studies, each using semi-structured interviews. Participants in studies 1 and 2 were RQDs within the first 4 years of qualification. In study 3, consultants who supervise medical students and trainees were interviewed. In study 4, participants were SPCCT members. I inductively applied Braun and Clarke’s method of reflective thematic analysis. While CoP and LoP theories informed the design of the studies, they were not applied in analysis until phase 3 of Braun and Clarke’s method (generation of initial themes). I sought latent themes and adopted a constructionist approach. In study 3, I also used a realist theory of supervised workplace learning in postgraduate training to examine the data. Results Fifteen RQDs, 14 consultants and 12 nursing and non-consultant medical members of acute hospital SPCCTs were interviewed. Cultural aspects in the workplace were powerful mediators of learning about EoL care. EoL care was not considered to be part of the core business of many physician teams and RQDs were often not supported by senior doctors to learn and develop capability in this area. When patients were identified as dying, what was perceived to be active care was withdrawn and RQDs were often left by their seniors to deliver the medical aspects of EoL care. The RQDs interviewed excused the perceived lack of consultants’ knowledge and skills in this area and their disengagement from patient care at the EoL. The consultant participants had set the bar high for entrustment in EoL communication. Opportunities for supported learning in the form of observation and less commonly participation, were predominantly reserved for senior trainees. Frequently the consultants interviewed failed to recognise that RQDs were involved in communication with patients and relatives towards the EoL and didn’t support their learning in this area. There was substantial variation in consultants’ approaches to EoL care. Dying was sometimes diagnosed late. This coupled with a lack of documentation of care plans to inform patient care out-of-hours, resulted in RQDs suffering moral distress when they were required to carry out burdensome investigations and treatments on dying patients. Emotion in a variety of forms was common in RQDs’ accounts. As RQDs moved teams frequently on their training journey they had to do the emotional work of adjusting to the local practice within each physician team. The on-call landscape was even more complex and RQDs had to deal with increased uncertainty and responsibility. SPCCT participants described their own struggles to gain legitimacy and trust with some physician teams. They noted RQDs’ lack of capability and their struggles in providing EoL care. They supported RQDs to develop knowledge and skills and provided emotional support.
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    Mapping the microbiota in hidradenitis suppurativa
    (University College Cork, 0022) McCarthy, Siobhán; O'Toole, Paul W.; Shanahan, Fergus; Murphy, Michelle
    Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by the formation of nodules, abscesses, and fistula at intertriginous sites. Pain, pruritus, malodour, and suppuration have a significant impact on quality of life for HS patients. The skin-gut axis is an area of emerging research in inflammatory skin disease and is a potential contributory factor to the pathogenesis of HS. Skin microbiome alterations in HS have become an area of expanding research with its role in the pathogenesis of HS becoming clearer. Gut microbiome alterations have been described in many inflammatory diseases including inflammatory bowel disease, rheumatoid arthritis, and cancer, but little is known about the gut microbiome in HS. Our hypothesis is that gut, as well as skin, microbiota alterations and their metabolites, may be responsible for skin inflammation in HS. The level of pain experienced by 150 patients with HS was measured using the visual analogue scale and EQ-5D-5L questionnaires. 59 patients with HS provided faecal samples, nasal and skin swabs of affected sites for analysis. These 59 patients also provided serum samples and completed questionnaires including the Dermatology Life Quality Index (DLQI), Morisky Medication Adherence Scale, International Physical Activity Questionnaire, and Food Frequency Questionnaire. 30 healthy controls provided fecal samples and 20 healthy controls provided nasal and skin swabs. We performed bacterial 16S rRNA gene amplicon sequencing on total DNA derived from the samples. Calprotectin was determined by enzyme-linked immunoassay (CALPROLAB™ Calprotectin ELISA (HRP). Complement C5a levels were assessed using enzyme-linked immunosorbent assay (Abcam ab193695 Complement C5a Human ELISA Kit). Pain was widely reported in 134 responders to the visual analog scale questionnaire. 82.1% reported some level of pain and 35.8% reported high levels of pain. In the EQ-5D-5L questionnaire, 81.4% of responders indicated that they felt pain or discomfort, and 31.0% expressed “severe” or “extreme” pain/discomfort. Weak correlation was seen between levels of pain and one marker of gut microbiota alpha diversity (Chao1), but this failed to be repeated for all indices of microbiota species richness. A significant impact on quality of life with a mean DLQI score of 12.15 (SD 7.67) was observed in patients with HS, which is in line with other severe dermatoses. 59% of patients reported a large or extremely large impact on their quality of life. The DLQI score did not correlate with gut microbial diversity. In this study, over 40% of patients with HS also reported some difficulty remembering to take their medications with 20% reporting that they forgot to take their medication in the previous 2 weeks. Patients with HS also reported moderate-to-high levels of physical activity; however this may be overestimated. Alterations in gut microbiota diversity did not correlate with levels of physical activity. Microbiome alpha diversity was significantly lower in the faecal, skin and nasal samples of individuals with HS which may be secondary to disease biology or related to antibiotic usage. Ruminococcus gnavus was more abundant in the faecal microbiome of individuals with HS, which is also reported in Crohn’s disease (CD), suggesting comorbidity due to shared gut microbiota alterations. No significant difference in faecal microbiota composition or overall habitual diet was seen in the patients with HS and diet was not associated with disease severity. Diet in HS was significantly different to controls, and similar to patients with CD. Finegoldia magna was over-abundant in HS skin samples relative to healthy controls. It is possible local inflammation is driven by F. magna through promoting the formation of neutrophil extracellular traps (NETs). 27.1% of patients with HS had a raised faecal calprotectin level of >50mg/kg with markedly elevated levels of >150mg/kg in 8.5% suggesting occult gastrointestinal inflammation. Median complement C5a level in patients with HS was elevated at 47 ng/ml (IQR 30.55 ng/ml) which is in keeping with prior studies. These alterations in both the gut and skin microbiome in HS warrant further exploration, and therapeutic strategies including faecal microbiota transplant or bacteriotherapy could be of benefit. Faecal calprotectin is a simple test which should be considered in patients with HS, with further investigations warranted in patients with elevated levels. C5a may provide a therapeutic target in patients with HS and serum C5a may act a biomarker of the disease.
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    Return to sport criteria post glenohumeral joint stabilisation in male contact and collision athletes
    (University College Cork, 2023) Fanning, Edel; Falvey, Eanna; Cools, Ann; Daniels, Katherine
    Background The path of return to contact and collision sports after glenohumeral joint stabilisation (GHJS) varies significantly among athletes. There are high rates of re-injury and associated fear and anxiety, especially among young male contact and collision athletes. Return-to-sport (RTS) decision-making can be complex for clinicians and physicians, with no consensus on the use of outcome measures following surgery for this cohort of athletes. In this thesis, I explore a battery of objective measures and psychological factors to aid RTS decision-making. Methods This thesis incorporates the work from four research questions (Chapters 3, 5, and 6) and a systematic review of the use of outcome measures following shoulder stabilisation in the athletic population (Chapter 2). The research comprises of observational cross-sectional and prospective longitudinal studies. For this thesis, I recruited un-injured and post-surgical stabilisation male contact and collision athletes. Data collection included force plate capture of upper quadrant performance tests, angle-specific isokinetic shoulder rotational strength, and psychological and shoulder-specific patient-reported outcome measures. Results The outcome variables of three upper quadrant performance tests (the countermovement push-up, press jump and drop box land) performed on dual force plates and angle-specific isokinetic shoulder rotational strength can be reliability measured in the male collision and contact athlete. Compared to an uninjured cohort, I identified strength and power deficits that persist post-GHJS in male contact and collision athletes. These results highlight the need to assess upper limb strength and power parameters post-GHJS, provide rehabilitation targets following surgery and could help reduce re-injury risk, although this needs further exploring. Finally, I demonstrated that psychological responses and self-reported outcome measures assessed before surgery and early recovery were not associated with time to RTS. However, at six months, lower psychological readiness scores identified athletes who returned to sport longer than 12 months. Conclusion This thesis adds novel insights into the use of strength and power measures and self-reported psychological outcome measures following GHJS in male contact and collision athletes. Targeting these outcomes may enhance rehabilitation and could play a role in injury prevention as athletes RTS.
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    Identification of bacteria-regulated mechanisms for the pathogenesis of inflammatory bowel diseases (IBD) and development of upconverting nanoparticle (UCNP) luminescence imaging for the monitoring of gut bacteria
    (University College Cork, 2022) Singh, Raminder; Melgar Villeda, Silvia; Andersson-Engels, Stefan; Shanahan, Fergus; Science Foundation Ireland; APC Microbiome Institute
    Inflammatory bowel disease (IBD) is a chronic inflammatory state of the gastrointestinal tract, including two inflammatory conditions Crohn’s disease (CD) and ulcerative colitis (UC). The environment, the gut microbiota, the genetic make-up and the immune response are believed to contribute to the aetiology of the disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are believed to exacerbate inflammation in patients with IBD. However, the literature demonstrates no consensus on the association between NSAID use and IBD, with some studies reporting that only high dose NSAID treatment are more likely for IBD exacerbation or relapse. In this study, using the piroxicam-accelerated model of colitis in interlukin-10 deficient (IL-10-/-) mice, we showed that mice fed 100 ppm piroxicam in food for 9 days (high dose) followed by 5 days of regular chow, develop colitis. The colitic phenotype was associated with activation of caspase-8, NLRP3 inflammasome and apoptosis and independent of initial gut microbiota. However, 5 days exposure (low dose) to 100 ppm piroxicam did not lead to colitis development. Adherent-invasive Escherichia coli (AIEC) is widely prevalent and heterogeneously present in the mucosa of IBD patients, particularly in Crohn’s disease. We hypothesise that the presence of AIEC in the gut of IBD patients might explain the NSAID-induced inflammation in IBD under low dose treatment (5 days piroxicam treatment). Indeed, 5 days piroxicam exposure was sufficient to induce colitis in AIEC-precolonised animals, indicating a synergism between AIEC colonisation and piroxicam treatment. Inhibition of NLR family pyrin domain containing 3 (NLRP3) or Caspase-8 activity ameliorated colitis. This synergism was lost under high dose piroxicam (9 days exposure) treatment. Our data indicate that under low dose NSAID treatment, AIEC can potentiate NSAID-induced inflammation in IL-10-/- mice by regulating the intestinal epithelial function and the immune response, highlighting its potential role in NSAID-induced inflammation in IBD patients exposed to low dose NSAIDs. Although, under high dose, NSAID itself is sufficient to induce colitis. This data suggests that the lack of consistency in the association between NSAID use and IBD could be explained by the NSAID dose and the presence of AIEC in the patients with IBD. Future studies should consider both these factors while studying association between NSAID use and symptomatic worsening in IBD. The role of microbes in IBD is supported by various studies performed in animal models where germ free mice are protected from intestinal inflammation. However, the precise interaction(s) between microbes and the host are not well understood. In vivo imaging techniques using custom designed fluorescent probes and bioluminescence have been classically used to track gut microbes. Several disadvantages while using fluorescent probes include autofluorescence, photobleaching and photodamage. To overcome these limitations, we propose to develop upconverting nanoparticles (UCNPs) luminescence imaging for monitoring of gut bacteria. Their unique property of photon upconversion enables them to convert low energy near-infrared (NIR) light into higher energy visible/NIR light offering greater tissue penetrance and signal-to-noise ratio. Here, we investigated the possibility of using UCNP 1) to image a single gut bacterium (e.g., AIEC) using UCNP-conjugated anti-E. coli antibody, and 2) to image the endogenous gut bacteria using metabolic labelling of bacterial peptidoglycan with azido-D-amino acids and strained-cyclooctynes such as Dibenzocyclooctyne (DBCO) -functionalised UCNPs. We showed a proof of principle for both these approaches using a fluorescent dye, but we were not able to replicate it with UCNP. Preliminary data suggests that the size difference between the UCNPs and the fluorescent dyes may be one of the potential reasons for lack of labelling. Future experiments should consider using smaller UCNPs and/or use a polyethylene glycol (PEG) linker between DBCO and UCNPs to increase the length of DBCO-UCNP construct and reduce the steric hinderance for better stability of UCNP-bacteria conjugation.
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    Rethinking stillbirth through behaviour change
    (University College Cork, 2022) Escañuela Sánchez, Tamara; O'Donoghue, Keelin; Matvienko-Sikar, Karen; Meaney, Sarah; Byrne, Molly; Science Foundation Ireland
    Background Worldwide, two million babies are stillborn every year. While the majority of stillbirths occur in low and middle-income countries, stillbirth is still one of the most common adverse pregnancy outcomes in high-income countries. In Ireland, the latest National Perinatal Mortality Clinical Audit report states a stillbirth rate of 4.20 per 1000 births for the year 2020, showing an increase compared to previous years. The belief that reduced stillbirth rates in high-income countries cannot be achieved is refuted by differences in stillbirth rates across different countries. Although not all stillbirths are preventable, there has been a call made in high-income countries to focus on risk factors for stillbirth, in order to reduce stillbirth rates. These risk factors include sociodemographic factors, medical factors, obstetric history-related factors, placental and fetal-related factors as well as behavioural and lifestyle-related factors. Some of these factors are modifiable through medical management or through behaviour change modification. This Thesis focuses on risk factors that have the potential to be modified through maternal behaviour change interventions: substance use (smoking, alcohol, and illicit drug use), high BMI, sleep position, and attendance at antenatal care. Strategies have been successfully implemented internationally to reduce stillbirth rates by designing and implementing care bundles that, amongst other elements, take into consideration the modifiable/behavioural risk factors for stillbirth. However, in Ireland, no such initiatives have been developed, although recommendations have been made that support their development. For behaviour change interventions or public health initiatives to have the best possible success in reducing the rates of stillbirth, they need to be designed with a solid evidence base. Hence, the overall objective of this Thesis was to build the evidence base to enhance the understanding of the modifiable behavioural risk factors for stillbirth and pregnancy. Further, this evidence base is needed to inform the future development of a behaviour change intervention that could be part of a care bundle with the objective of reducing stillbirth rates in Ireland. Methodology To address the Thesis´s aims, both qualitative and quantitative methods were utilised. Applying multiple methods to explore a phenomenon provides flexibility to analyse different aspects of it in the different studies. Initially, a non-systematic review of the literature was conducted to identify the target behavioural risk factors that this project was going to focus on (Chapter 2). A website quantitative content analysis was conducted to assess the availability of information related to stillbirth and behavioural risk factors for stillbirth in Irish and UK websites (Chapter 3). For this study, descriptive and inferential statistics were utilised. Further, three systematic qualitative meta-synthesis were conducted to identify facilitators and barriers to modify identified behavioural risk factors according to the pregnant women’s experience (Chapters 4-6). A meta-ethnographic approach as described by Noblit and Hare was adopted to conduct these qualitative meta-syntheses. Reflexive Thematic Analysis as described by Braun and Clarke, with a constructivist approach, was used to conduct a qualitative semi-structured interview study with postpartum women about their experiences of stillbirth information provision and behaviour change during their antenatal care (Chapter 7). Finally, a systematic review of interventions designed in the context of stillbirth prevention that targeted behavioural risk factors was conducted (Chapter 8). This systematic review had the objective of identifying which behaviour change techniques (BCTs) have been used to date. Results The findings of the literature review (Chapter 2) showed that the modifiable behavioural risk factors with the strongest evidence of associations with stillbirth were substance use, smoking, heavy drinking and illicit drug use, lack of attendance and compliance with antenatal care, weight-related risks, and sleep position. The quantitative content analysis of websites (Chapter 3) revealed that information about stillbirth and behavioural risk factors for stillbirths was scarce on websites directed at the pregnant population, with only one website containing all the information sought. Five main areas of concern were identified across the three meta-synthesis of qualitative research of facilitators and barriers influencing women’s prenatal health behaviours (Chapters 4-6), regardless of the behaviour explored: 1) health literacy, awareness of risks and benefits; 2) insufficient and overwhelming sources of information; 3) lack of opportunities and healthcare professionals attitudes interfering with communication & discussion; 4) social influence of environment, and 5) social judgement, stigmatisation of women and silence around stillbirth. Further, the qualitative study with postpartum women (Chapter 7) revealed that women perceived behaviour change during pregnancy as easy and natural, as they were focused on obtaining the best outcomes for their babies. Although women had high levels of awareness regarding health advice, their awareness about stillbirth was very limited. Women reported a lack of discussion about stillbirth and behavioural risk factors during their antenatal care; however, most women showed a positive disposition towards receiving this information because “knowledge is key”, as long as it is done in a “sensible manner”. The systematic review of interventions designed in the context of stillbirth prevention identified nine relevant interventions. From the BCT coding, it was established that the most common BCT used was “information about health consequences”, followed by “adding objects to the environment” (Chapter 8). Conclusion This research makes a valuable contribution to the understanding of the maternal behaviours associated with an increased risk of stillbirth, and it provides a necessary evidence-base to inform future prevention strategies to reduce rates of stillbirth in Ireland and in similar healthcare settings. This research sought to incorporate women’s voices and use research methods to produce high-quality results that meet the research objectives. The findings from the studies in this Thesis support four overarching topics and highlight issues related to 1) health literacy and sources of information, 2) relationships with healthcare professionals (HCPs), 3) healthcare systems and structural barriers, and 4) interpersonal, social and structural factors. In response to the research findings, several recommendations are made in relation to policy, practice and research which are grounded on women’s experiences during pregnancy. Regarding policy, these recommendations include improving education and information sources for women and HCPs, providing pregnancy-specific supports, utilising community services to support women with behaviour change, and developing a care bundle to tackle the behavioural risk factors for stillbirth. Furthermore, the work practice recommendations made include developing clinical guidelines to support HCPs in providing care to pregnant women, and prioritising health promotion during antenatal care. These priorities might also serve to help funders and researchers to design and conduct policy-relevant research. The key future research areas identified by this Thesis are in relation to the involvement of PPI representatives, the assessment of the quality of the available sources of information and the further exploration of potential facilitators and barriers to modifying pregnant women’s sleeping position from a qualitative perspective. In addition, this Thesis proposes a detailed process to continue building on the work set out in the different studies to develop a pregnancy-specific behaviour change intervention for the modifiable behavioural risk factors for stillbirth in the future.