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  • Storytelling and poetry in the time of coronavirus.

    Barrett, Elizabeth; Dickson, Melissa; Hayes-Brady, Clare; Wheelock, Harriet (2020-05-14)
    The coronavirus crisis occurs at a time when many clinicians have already experienced burnout. One in three Irish doctors were suffering from burnout in the 2019 National Study of Wellbeing of Hospital Doctors in Ireland; rates are also high in Irish Psychiatry. We present a perspective on the use of narrative in medicine and recognise that storytelling, and the patient history are very much at the heart of medicine. Clinician storytelling, such as Schwartz Rounds and Balint group work, has very much come to the fore in Irish Psychiatry and in training. Projects such as MindReading have explored overlaps between clinicians, humanities experts and experts by experience. We give an overview of some approaches from the movement around narrative in medicine to bolster this. We explore why clinicians write as ways to support identification, catharsis and a way to process experiences. Clinicians and patients may also use literature and poetry to promote coping. The historical context and practical strategies are highlighted, particularly with reference to poetry use during the current crisis.
  • Sepsis at ICU admission does not decrease 30-day survival in very old patients: a post-hoc analysis of the VIP1 multinational cohort study.

    Ibarz, Mercedes; Boumendil, Ariane; Haas, Lenneke E M; Irazabal, Marian; Flaatten, Hans; de Lange, Dylan W; Morandi, Alessandro; Andersen, Finn H; Bertolini, Guido; Cecconi, Maurizio; et al. (2020-05-13)
    Background: The number of intensive care patients aged ≥ 80 years (Very old Intensive Care Patients; VIPs) is growing. VIPs have high mortality and morbidity and the benefits of ICU admission are frequently questioned. Sepsis incidence has risen in recent years and identification of outcomes is of considerable public importance. We aimed to determine whether VIPs admitted for sepsis had different outcomes than those admitted for other acute reasons and identify potential prognostic factors for 30-day survival. Results: This prospective study included VIPs with Sequential Organ Failure Assessment (SOFA) scores ≥ 2 acutely admitted to 307 ICUs in 21 European countries. Of 3869 acutely admitted VIPs, 493 (12.7%) [53.8% male, median age 83 (81-86) years] were admitted for sepsis. Sepsis was defined according to clinical criteria; suspected or demonstrated focus of infection and SOFA score ≥ 2 points. Compared to VIPs admitted for other acute reasons, VIPs admitted for sepsis were younger, had a higher SOFA score (9 vs. 7, p < 0.0001), required more vasoactive drugs [82.2% vs. 55.1%, p < 0.0001] and renal replacement therapies [17.4% vs. 9.9%; p < 0.0001], and had more life-sustaining treatment limitations [37.3% vs. 32.1%; p = 0.02]. Frailty was similar in both groups. Unadjusted 30-day survival was not significantly different between the two groups. After adjustment for age, gender, frailty, and SOFA score, sepsis had no impact on 30-day survival [HR 0.99 (95% CI 0.86-1.15), p = 0.917]. Inverse-probability weight (IPW)-adjusted survival curves for the first 30 days after ICU admission were similar for acute septic and non-septic patients [HR: 1.00 (95% CI 0.87-1.17), p = 0.95]. A matched-pair analysis in which patients with sepsis were matched with two control patients of the same gender with the same age, SOFA score, and level of frailty was also performed. A Cox proportional hazard regression model stratified on the matched pairs showed that 30-day survival was similar in both groups [57.2% (95% CI 52.7-60.7) vs. 57.1% (95% CI 53.7-60.1), p = 0.85]. Conclusions: After adjusting for organ dysfunction, sepsis at admission was not independently associated with decreased 30-day survival in this multinational study of 3869 VIPs. Age, frailty, and SOFA score were independently associated with survival.
  • Mindfulness moments for clinicians in the midst of a pandemic.

    Hedderman, E; O'Doherty, V; O'Connor, S (2020-05-21)
    Clinicians are routinely subjected to intense and stressful working environments, and the current COVID-19 crisis increases their risk of psychological distress. Mindfulness has been shown to improve life satisfaction, resilience to stress, self-compassion, compassion and general well-being in healthcare workers. Based on their clinical experience, the authors present mindfulness moments for clinicians (MMFC), a selection of short, simple and accessible mindfulness practices to promote resilience and compassion among clinicians working in this pandemic. The practices can be used on the job and are accessible to both novice and experienced meditators. Most of these practices are extracted from evidence-based mindfulness programmes. Further research is indicated to assess the effectiveness of using MMFC to support clinicians in their work and to promote resilience.
  • Emerging treatments for inflammatory bowel disease.

    Hazel, Karl; O'connor, Anthony (2020-02-05)
    Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation, a relapsing and remitting clinical course, requirement for lifelong medication and often, significant morbidity. While multiple effective therapeutic options exist for the treatment of IBD, a proportion of patients will either fail to respond or lose response to therapy. Advances in therapeutics, such as the gut-specific anti-integrins, now offer patients an alternative option to systemic immunosuppression. Anti-interleukin 12 (anti-IL-12)/IL-23 agents offer new and effective treatment options for CD, while the oral small molecules now offer an oral alternative for the treatment of moderate-to-severe disease, previously requiring subcutaneous injection or intravenous infusion. Alternatives to pharmacological treatment such as stem-cell transplant and faecal microbiota transplant are also showing some promise in the treatment of both CD and UC.
  • Sepsis Associated Delirium.

    Atterton, Ben; Paulino, Maria Carolina; Povoa, Pedro; Martin-Loeches, Ignacio (2020-05-18)
    Sepsis is a potentially life-threatening condition caused by a systemic dysregulated host response to infection. The brain is particularly susceptible to the effects of sepsis with clinical manifestations ranging from mild confusion to a deep comatose state. Sepsis-associated delirium(SAD) is a cerebral manifestation commonly occurring in patients with sepsis and is thought to occur due to a combination of neuroinflammation and disturbances in cerebral perfusion, the blood brain barrier (BBB) and neurotransmission. The neurological impairment associated with SAD can persist for months or even longer, after the initial septic episode has subsided which may impair the rehabilitation potential of sepsis survivors. Early identification and treatment of the underlying sepsis is key in the management of SAD as once present it can be difficult to control. Through the regular use of validated screening tools for delirium, cases of SAD can be identified early; this allows potentially aggravating factors to be addressed promptly. The usefulness of biomarkers, neuroimaging and electroencephalopathy (EEG) in the diagnosis of SAD remains controversial. The Society of Critical Care Medicine (SCCM) guidelines advise against the use of medications to treat delirium unless distressing symptoms are present or it is hindering the patient’s ability to wean from organ support.
  • Down syndrome and oral health: mothers' perception on their children's oral health and its impact.

    AlJameel, AlBandary H; Watt, Richard G; Tsakos, Georgios; Daly, Blánaid (2020-06-16)
    Background: Individuals with Down syndrome exhibit particular oro-facial characteristics that may increase their risk of oral health problems. However, there is little research on the oral health of children and adults with Down syndrome and the way that oral health may affect Quality of Life (QoL). This study explored mothers' perceptions of the oral health problems experienced by their children with Down syndrome and how these reported problems impacted the lives of the children and their families. Methods: The study involved 20 in-depth, semi-structured interviews with mothers of children and adolescents aged 12-18 years with Down syndrome attending special care centres in Riyadh, Saudi Arabia. Results: The predominant oral-health related problem reported by mothers was difficulty in speaking. Mothers also reported that tooth decay and toothache were problems that had undesirable effects on different aspects of their children's QoL including: performing daily activities, emotional wellbeing, and social relationships. Poor oral health and functional problems had direct and indirect impacts on the family's QoL as well. Conclusion: Mothers perceived an array of QoL impacts from oral conditions, which affected their child with Down syndrome and the wider family.
  • A prospective cohort study of the conservative management of focal cervical intraepithelial neoplasia 2.

    McMahon, Gabriela; Griffin, Sinead; Curley, Jennifer; Hartel, Paul; Kilgallen, Clive; Kondaveeti, Nirmala; Sligo University Hospital (European Society of Gynaecology, 2020)
    Background and Purpose: Traditionally, cervical intraepithelial neoplasia 2 (CIN 2) is managed by the removal of affect-ed tissue in a procedure known as a large loop excision of the transformation zone (LLETZ). In our unit, pathology reports on LLETZ specimens done for a diagnosis of CIN 2 often are reported as CIN 1 or a normal result. So we wondered – are we over-managing CIN 2? Methods: This study was designed to assess the acceptability and outcomes of the conservative management of focal CIN 2. We wanted to establish if monitoring of the disease is sufficient in selected women. In this prospective cohort, women were selected for inclusion in the study by having a histological diagnosis of focal CIN 2 from a cervical biopsy and after discussion at the colposcopy multi-disciplinary team meeting. After explanation of CIN 2 and its future impli-cations, women were informed of the risks and benefits of conservative management versus LLETZ. Women who opted for conservative management were seen in the colposcopy clinic for colposcopy examination, cervical biopsy ± cervical smear and HPV testing at six monthly intervals for two years.Results: Over the two-year follow-up period, 20/31 women (64.5%) had regression of disease, 7/31 women (22.6%) had persistence of CIN 2 and 4/31 women (12.9%) had progression of disease to CIN 3. There were no reported cases of cervical carcinoma in situ or invasive cervical carcinoma. During the follow-up period, patients were offered treatment if there was progression to CIN 3 or worse, persistence of CIN 2 or if they wished to undergo treatment at any stage.Conclusions: Conservative management of CIN 2 may be considered in women who are under the age of 30 with focal CIN 2. However, larger studies should be carried out to define the safety or acceptability of changing this practice.
  • Involving Clients to Inform Development and Implementation of Combined Type 2 Diabetes and Chronic Kidney Disease Care Using Discovery Interview Technique.

    Blanchfield, Denise; O'Connor, Laserina (Innovational Publishers, 2020-10)
    The development of chronic kidney disease in persons with Type 2 diabetes has been described as an epidemic. Standard outpatient care for these associated conditions is routinely provided separately, resulting in missed opportunities to implement preventative and early management strategies. Historically, care delivery for these combined conditions has fallen within the remit of medical professionals, evidenced by a dearth of information pertaining to the contribution of advanced practice nursing for this cohort. Clients report an uncoordinated impersonal approach to care delivery for associated conditions, however incorporating their experience is vital to the delivery of patient centered care and will be included in this study through their stories. The primary aim of this participatory action research (PAR) study is to utilize the client care stories and health-care professional perspectives to inform development and implementation of a new combined Type 2 diabetes and chronic kidney disease service in the context of advanced practice nursing. Methodology: This study adopted a PAR approach informed by patient discovery interviews and key stakeholders focus groups. Transcripts will be developed from discovery interviews and focus groups and analyzed using thematic analysis. Results: The PAR will utilize thematic analysis outcomes to inform the primary aim and clinical outcomes from combined care will be evaluated after 9 months by retrospective chart review. Conclusion: The approach adopted in this study represents a departure from traditional medically led care strategies. Outcomes may elucidate potential challenges to the development and delivery of innovative care delivery for underserved patient cohorts in the context of advanced practice nursing.
  • Beaumont Hospital and National Ambulance Service: Pathfinder Service

    Corcoran, Grace; Kenna, Lawrence; Beaumont Hospital, National Ambulance Service (Beaumont Hospital, 2020-02-26)
    Presentation on integration of ambulance service and Beaumont Hospital ED.
  • Covid-19: safe PPE - hand hygiene first in all cases.

    University of Limerick Hospitals (University pf Limerick Hospitals, 2020-04-03)
    Care of patients with respiratory symptoms/ suspected/confirmed COVID-19.
  • Musculoskeletal anomalies in children with Down syndrome: an observational study.

    Foley, Charlene; Killeen, Orla G (2018-11-24)
    Background: Musculoskeletal complications of Down syndrome (DS) are common but infrequently reported. The combination of ligamentous laxity and low muscle tone contributes to increased risk of a number of musculoskeletal disorders and a delay in acquisition of motor milestones. The primary aim of this study was to describe musculoskeletal anomalies reported in a national cohort of children with DS. Methods: This was an observational study. Children with DS, aged 0-21 years, were invited to attend a musculoskeletal assessment clinic conducted by a paediatric physician. Relevant musculoskeletal history and clinical findings were documented. Results: Over an 18-month period, 503 children with DS were examined (56% male). The median age was 8.1 years (0.6-19.2). Pes planus was almost universal, occurring in 91% of the cohort. A range of other musculoskeletal anomalies were observed, with inflammatory arthritis (7%) and scoliosis (4.8%) occurring most frequently after pes planus. Delay in ambulation was common; the median age to walk was 28 months (12-84). Conclusion: Children with DS are at increased risk of a number of potentially debilitating musculoskeletal problems. These conditions can present in variable manners or be completely asymptomatic. Pes planus is common; therefore, early consideration of orthotics and lifelong appropriate supportive footwear should be considered. Delayed ambulation is frequently noted. A significant proportion of children with DS have arthritis; however, despite a high prevalence, it is often missed, leading to delayed diagnosis. An annual musculoskeletal assessment for all children with DS could potentially enable early detection of problems, allowing for timely multidisciplinary team intervention and better clinical outcomes.
  • Perinatal factors affect the gut microbiota up to four years after birth.

    Fouhy, Fiona; Watkins, Claire; Hill, Cian J; O'Shea, Carol-Anne; Nagle, Brid; Dempsey, Eugene M; O'Toole, Paul W; Ross, R Paul; Ryan, C Anthony; Stanton, Catherine (2019-04-03)
    Perinatal factors impact gut microbiota development in early life, however, little is known on the effects of these factors on microbes in later life. Here we sequence DNA from faecal samples of children over the first four years and reveal a perpetual evolution of the gut microbiota during this period. The significant impact of gestational age at birth and delivery mode on gut microbiota progression is evident in the first four years of life, while no measurable effects of antibiotics are found in the first year. Microbiota profiles are also characteristic in children dependant on gestational age and maturity. Full term delivery is characterised by Bacteroides (year one), Parabacteroides (year two) and Christensenellaceae (year four). Preterm delivery is characterised by Lactobacillus (year one), Streptococcus (year two) and Carnobacterium (year four). This study reveals that the gut retains distinct microbial profiles of perinatal factors up to four years of age.
  • The Role of Religion in Buffering the Impact of Stressful Life Events on Depressive Symptoms in Patients with Depressive Episodes or Adjustment Disorder.

    Lorenz, Louisa; Doherty, Anne; Casey, Patricia (2019-04-08)
    Most studies into the role of religiousness in relation to depression severity have mainly found an inverse relationship between greater religiousness and lower levels of depressive symptoms. There is reason to assume that religiousness has a buffering effect on the relationship between stressful life events and depressive symptoms. The aim of this study was to investigate the role of religiousness in moderating the impact of stressors on depressive symptoms. n = 348 patients with either a depressive episode or adjustment disorder were assessed at referral to the liaison psychiatry services in three Dublin hospitals and n = 132 patients were followed up six months later. We assessed depressive symptoms, life events, social support, and religiosity, and used hierarchical and multiple linear regression for data analysis. The interaction of organised religious activity and the amount of life events was significant (β = -0.19, p = 0.001) in the cross-sectional prediction of depressive symptoms while non-organised religious activity (β = -0.23, p = 0.001) and intrinsic religiousness (β = -0.15, p = 0.033) interacted significantly with life events in the longitudinal analysis. This study demonstrated that various dimensions of religiousness buffered the impact of life events on outcome.
  • Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study.

    Hagens, Eliza R C; van Berge Henegouwen, Mark I; van Sandick, Johanna W; Cuesta, Miguel A; van der Peet, Donald L; Heisterkamp, Joos; Nieuwenhuijzen, Grard A P; Rosman, Camiel; Scheepers, Joris J G; Sosef, Meindert N; et al. (2019-07-04)
    Background: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. Methods: The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. Discussion: The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics.
  • Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability.

    Verheije, Rosalind; Kupchik, Gabriel S; Isidor, Bertrand; Kroes, Hester Y; Lynch, Sally Ann; Hawkes, Lara; Hempel, Maja; Gelb, Bruce D; Ghoumid, Jamal; D'Amours, Guylaine; et al. (2018-10-05)
    Deletions on chromosome 15q14 are a known chromosomal cause of cleft palate, typically co-occurring with intellectual disability, facial dysmorphism, and congenital heart defects. The identification of patients with loss-of-function variants in MEIS2, a gene within this deletion, suggests that these features are attributed to haploinsufficiency of MEIS2. To further delineate the phenotypic spectrum of the MEIS2-related syndrome, we collected 23 previously unreported patients with either a de novo sequence variant in MEIS2 (9 patients), or a 15q14 microdeletion affecting MEIS2 (14 patients). All but one de novo MEIS2 variant were identified by whole-exome sequencing. One variant was found by targeted sequencing of MEIS2 in a girl with a clinical suspicion of this syndrome. In addition to the triad of palatal defects, heart defects, and developmental delay, heterozygous loss of MEIS2 results in recurrent facial features, including thin and arched eyebrows, short alae nasi, and thin vermillion. Genotype-phenotype comparison between patients with 15q14 deletions and patients with sequence variants or intragenic deletions within MEIS2, showed a higher prevalence of moderate-to-severe intellectual disability in the former group, advocating for an independent locus for psychomotor development neighboring MEIS2.
  • Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis.

    Wade, Sarah M; Canavan, Mary; McGarry, Trudy; Low, Candice; Wade, Siobhan C; Mullan, Ronan H; Veale, Douglas J; Fearon, Ursula (2019-01-09)
    PsA synovial tissue infiltrating CD4+ T-cells expressed higher levels of interleukin (IL)-17A, interferon gamma (IFN-γ), GM-CSF and CD161, with parallel enrichment of Th1, Th17 and exTh17 T-helper subsets (all p<0.05). Interestingly, a significant proportion of synovial T-cell subsets were triple-positive for GM-CSF, tumour necrosis factor (-TNF), -IL-17 or IFN-γ compared with matched blood (all p<0.05). Importantly, frequencies of polyfunctional T-cells correlated with DAPSA: Th1-GM-CSF+/TNF+/IFN-γ+ (r=0.7, p<0.01), Th17-GM-CSF+/TNF+/IL-17+ (r=0.6, p<0.057) and exTh17-GM-CSF+/TNF+/IFN-γ+ (r=0.7, p=0.0096), with no associations observed for single cytokine-producing T-cells. Following ex vivo culture of PsA synovial tissue cell suspensions, polyfunctional GM-CSF+TNFα+IL-17A+ or/IFN-γ+-producing T-cells (p<0.05), but not single cytokine-producing T-cells, were inhibited with a PDE4 inhibitor. Conclusion: These data demonstrate enrichment of polyfunctional T-cells in PsA synovial tissue which were strongly associated with DAPSA and ex vivo therapeutic response.
  • KAT6A Syndrome: genotype-phenotype correlation in 76 patients with pathogenic KAT6A variants.

    Kennedy, Joanna; Goudie, David; Blair, Edward; Chandler, Kate; Joss, Shelagh; McKay, Victoria; Green, Andrew; Armstrong, Ruth; Lees, Melissa; Kamien, Benjamin; et al. (2018-09-24)
    Purpose: Pathogenic variants in KAT6A have recently been identified as a cause of syndromic developmental delay. Within 2 years, the number of patients identified with pathogenic KAT6A variants has rapidly expanded and the full extent and variability of the clinical phenotype has not been reported. Methods: We obtained data for patients with KAT6A pathogenic variants through three sources: treating clinicians, an online family survey distributed through social media, and a literature review. Results: We identified 52 unreported cases, bringing the total number of published cases to 76. Our results expand the genotypic spectrum of pathogenic variants to include missense and splicing mutations. We functionally validated a pathogenic splice-site variant and identified a likely hotspot location for de novo missense variants. The majority of clinical features in KAT6A syndrome have highly variable penetrance. For core features such as intellectual disability, speech delay, microcephaly, cardiac anomalies, and gastrointestinal complications, genotype- phenotype correlations show that late-truncating pathogenic variants (exons 16-17) are significantly more prevalent. We highlight novel associations, including an increased risk of gastrointestinal obstruction. Conclusion: Our data expand the genotypic and phenotypic spectrum for individuals with genetic pathogenic variants in KAT6A and we outline appropriate clinical management.
  • Reproductive health outcomes in women with psoriatic arthritis.

    Murray, Kieran; Moore, Louise; McAuliffe, Fionnuala; Veale, Douglas J (2019-02-15)
  • Clinical and genetic landscape of treatment naive cervical cancer: Alterations in PIK3CA and in epigenetic modulators associated with sub-optimal outcome.

    Scholl, Suzy; Popovic, Marina; de la Rochefordiere, Anne; Girard, Elodie; Dureau, Sylvain; Mandic, Aljosa; Koprivsek, Katarina; Samet, Nina; Craina, Marius; Margan, Madalin; et al. (2019-04-02)
    Background: There is a lack of information as to which molecular processes, present at diagnosis, favor tumour escape from standard-of-care treatments in cervical cancer (CC). RAIDs consortium (, conducted a prospectively monitored trial, [BioRAIDs (NCT02428842)] with the objectives to generate high quality samples and molecular assessments to stratify patient populations and to identify molecular patterns associated with poor outcome. Methods: Between 2013 and 2017, RAIDs collected a prospective CC sample and clinical dataset involving 419 participant patients from 18 centers in seven EU countries. Next Generation Sequencing has so far been carried out on a total of 182 samples from 377 evaluable (48%) patients, allowing to define dominant genetic alterations. Reverse phase protein expression arrays (RPPA) was applied to group patients into clusters. Activation of key genetic pathways and protein expression signatures were tested for associations with outcome. Findings: At a median follow up (FU) of 22 months, progression-free survival rates of this FIGO stage IB1-IV population, treated predominantly (87%) by chemoradiation, were65•4% [CI95%: 60•2-71.1]. Dominant oncogenic alterations were seen in PIK3CA (40%), while dominant suppressor gene alterations were seen in KMT2D (15%) and KMT2C (16%). Cumulative frequency of loss-of-function (LOF) mutations in any epigenetic modulator gene alteration was 47% and it was associated with PIK3CA gene alterations in 32%. Patients with tumours harboring alterations in both pathways had a significantly poorer PFS. A new finding was the detection of a high frequency of gains of TLR4 gene amplifications (10%), as well as amplifications, mutations, and non-frame-shift deletions of Androgen receptor (AR) gene in 7% of patients. Finally, RPPA protein expression analysis defined three expression clusters. Interpretation: Our data suggests that patient population may be stratified into four different treatment strategies based on molecular markers at the outset. FUND: European Union's Seventh Program grant agreement No 304810.

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