Research by staff affiliated to St. James's Hospital

Recent Submissions

  • Acquired Factor Xiii Deficiency: An Uncommon But Easily Missed Cause Of Severe Bleeding

    Fogarty, H; Byrne, M; O’Connell, NM; Ryan, K; White, B; O’Donnell, JS; Lavin, M (Irish Medical Journal, 2018-05)
    Factor XIII (FXIII) is a plasma clotting protein involved in clot stabilization. Severe FXIII deficiency may present with severe, even fatal bleeding. Critically however, routine coagulation assays may be normal and only specific FXIII assays will detect the abnormality. Herein we discuss a case report of a patient with acquired FXIII deficiency in order to highlight the clinical challenges associated with establishing the diagnosis and discuss the treatment approach. A 70-year-old man presented with a gluteal haematoma despite no preceding personal history of bleeding. Extensive initial haemostatic investigations were normal until a specific FXIII assay showed a marked reduction in FXIII levels. With directed treatment, bleeding episodes ceased and remission was achieved. Clinical awareness of FXIII deficiency is important, so appropriate testing can be implemented in patients with unexplained bleeding diatheses, particularly those in whom bleeding responds poorly to standard replacement therapy.
  • Therapeutics Today May 2018 Number 5

    National Medicines Information Centre, St. James’s Hospital (SJH) Dublin 8 (National Medicines Information Centre, St. James’s Hospital (SJH) Dublin 8, 2018-05)
  • Therapeutics Today April 2018 Number 4

    National Medicines Information Centre, St. James’s Hospital; Dept of Therapeutics Trinity College, Trinity Centre, SJH (National Medicines Information Centre, St. James’s Hospital, 2018-04)
    Newsletter of the National Medicines Information Centre, St. James’s Hospital.
  • The ‘Medication Safety Minute’− Microlearning in Medicine

    Relihan, Eileen (2018-04-06)
    Summary of an initiative of St. James’s Hospital (SJH) medication safety programme to highlighting prescribing safety issues. The project the ‘Medication Safety Minute' was based on the concept of ‘bite-sized learning’. The aim was to deliver a message which could be which could be read and understood in one minute or less. The project was selected for the HSE excellence awards showcase.
  • Methaemoglobinaemia: A Blue Light Emergency

    Uí Bhroin, S; McNamara, R; Kidney, E (Irish Medical Journal, 2018-03)
    Methaemoglobinaemia is a rare but potentially fatal condition. It occurs when the haem molecule of haemoglobin is oxidized from ferrous to ferric form1,2. Methaemoglobin has decreased oxygen carrying capacity. It also causes leftward shift of the oxygen dissociation curve, thus impairing tissue oxygenation1,2. Methaemoglobinaemia can be congenital or, more commonly, acquired3. Many toxins have been implicated in acquired methaemoglobinaemia including local anaesthetics, metoclopramide, cocaine and volatile nitrites4,5.
  • Portal Hypertensive Colopathy with Pelvic Varices presenting as Severe Lower GI Bleed treated with TIPSS

    Murphy, SF; Durand, M; McMorrow, JP; Meaney, JF; Guiney, M (Irish Medical Journal, 2018-02)
    We present the case of a 71-year-old lady with a background of significant alcohol intake who presented with frank lower gastrointestinal (GI) bleeding, lower abdominal pain and haemoglobin 6.3g/dL. CT abdominal angiogram showed right-sided colonic thickening, atrophic liver and enlarged superior mesenteric vein (SMV) and right-sided pelvic varix. This lead to a diagnosis of portal hypertensive colopathy secondary to alcoholic liver cirrhosis. The patient failed conservative management and underwent a Transjugular Intrahepatic Portosystemic Shunt (TIPSS) procedure. This lead to an immediate resolution of her lower-GI bleeding. Repeat CT at three weeks showed a decompressed SMV and resolution of the right-sided pelvic varix. The patient was discharged after three months following optimization of medical condition and social circumstances.
  • Outcomes of a Community-Based Paediatric Weight Management Programme in an Irish Midlands Setting

    Bennett, AE; Johnston Molloy, C; Glennon-Slattery, C; Loane, D (Irish Medical Journal, 2018-02)
    Ongoing investigation is needed into feasible approaches which reduce excess weight in childhood. This study aimed to assess the effectiveness of an adapted version of the Scottish Childhood Overweight Treatment Trial (SCOTT) in an Irish primary care setting. Families were offered monthly dietitian-led sessions for six months. These sessions targeted dietary habits, family meals, screen time and exercise. Of the 95 children (mean age 7.6 years) referred, 90.5% (n86) were obese and 9.5% (n9) were overweight. Fifty-one (53.7%) families opted into the programme from referral, and 18 completed the programme (64.7% attrition). Statistically significant reductions in body mass index (BMI) were observed between sessions one and six (25.7±4.2kg/m2 and 25.3±4.8kg/m2, respectively, p<0.01). BMI z-score modestly decreased by 0.2 (p=0.01). Despite these reductions, issues with programme referral, attrition and long-term effectiveness were evident. Further investigation into strategies which reduce paediatric overweight is warranted.
  • Laryngeal Chondrosarcoma: A rare cause of critical upper airway obstruction.

    Tuite, K; Oosthuizen, J.C; Subramaniam, T; Kinsella, J.B (Irish Medical Journal, 2018-01)
    Laryngeal cancers are rare, encompassing around one percent of all cancers. Suspicion should be raised if a patient presents with classical signs and symptoms; i.e. dysphonia, inspiratory stridor, dysphagia, odynophagia, neck mass, or persistent cough. Laryngeal chondrosarcoma is a rare form of laryngeal cancer, the diagnosis of which can be difficult. The case in question describes an unusual presentation of one such case, and its subsequent investigation, management and outcome.
  • Incorporating Oral Health as Part of Routine Diabetes Care in Ireland

    Ahern, J; Hamnvik, OP; Barrow, J; Nunn, J (Irish Medical Journal, 2017-11)
    Diabetes mellitus is a common disorder of glucose metabolism that is increasingly prevalent in the Irish population. It is associated with a range of complications leading to substantial morbidity and mortality. A less well-recognized complication of diabetes is periodontal disease. This is a chronic inflammatory disease affecting the periodontium, the specialized group of tissues that surround and support the teeth, including the gingiva (gums) and alveolar bone. Periodontal disease affects patients with diabetes with a greater prevalence and incidence than non-diabetic patients, and can itself exert negative effects on glucose control in people with diabetes. The National Clinical Programme for Diabetes in Ireland aims to reduce the morbidity and mortality associated with diabetes, which includes the development and dissemination of guidelines supporting integrated care. Based on the bidirectional relationship between diabetes mellitus and periodontal disease, we recommend that an oral health evaluation, as well as any necessary onward referral, be incorporated into the Irish recommendations for routine diabetes care, as part of the National Clinical Programme.
  • Interventions to Improve the Treatment of Malaria in an Acute Teaching Hospital in Ireland

    O’Connor, R; Morley, D; Relihan, E; Broderick, A; Merry, C; Bergin, C (Irish Medical Journal, 2017-11)
    Malaria is the most serious parasitic infection. At our institution over a two year period there were treatment errors in 18% (n=3) of cases. The aim of this multidisciplinary study was to ensure appropriate and timely treatment of malaria by implementation of a cluster of interventions: reconfiguration of existing guidelines, provision of prescribing information; delivery of education sessions to front-line staff and enabling rapid access to medication. Staff feedback was assessed through a questionnaire. Perceived benefits gained included awareness of guidelines (91%, n= 39), how to diagnose (81%, n =35), how to treat (86%, n=37), that treatment must be prompt (77%, n=33) and where to find treatment out of hours (84%, n=36). ‘Others’ perceived benefits (5% n= 2) noted referred to treatment in pregnancy. Going forward, a programme of on-going staff education, repeated audits of guideline compliance and promotion of reporting of medication errors should help ensure that these benefits are sustained
  • Trends in surgical mortality following colorectal resection between 2002 and 2012: A single-centre, retrospective analysis.

    Stephens, I; Stuart, C; Stephens, R; McCormick, P; Larkin, J; Mehigan, B (Irish Medical Journal, 2017-06)
    Surgical mortality is a commonly-used measurement of surgical risk. It is imperative that patients receive accurate, up-to-date information regarding operative risk. To date, studies investigating temporal changes in surgical mortality following colorectal resection in Ireland have been limited. This retrospective study investigates such trends in one of the eight centres for symptomatic and screen-detected colorectal cancers in Ireland, across an 11-year period. A steady decline in surgical mortality was found across this time, showing a significant difference in rates before and after centralisation of rectal cancer care and the advent of colorectal surgery as a surgical specialisation (5.2%, 1.52%). This has important implications for the organisation of colorectal cancer care in Ireland.
  • Physiotherapy ‘Great Place to Work’ Initiative Survey

    Murphy, Niamh; Physiotherapy Department, St James’s Hospital (Physiotherapy Department, St James’s Hospital, 2014-10)
  • MicroRNA-330-5p as a Putative Modulator of Neoadjuvant Chemoradiotherapy Sensitivity in Oesophageal Adenocarcinoma.

    Bibby, Becky A S; Reynolds, John V; Maher, Stephen G (PLoS ONE, 2015)
    Oesophageal adenocarcinoma (OAC) is the sixth most common cause of cancer deaths worldwide, and the 5-year survival rate for patients diagnosed with the disease is approximately 17%. The standard of care for locally advanced disease is neoadjuvant chemotherapy or, more commonly, combined neoadjuvant chemoradiation therapy (neo-CRT) prior to surgery. Unfortunately, ~60-70% of patients will fail to respond to neo-CRT. Therefore, the identification of biomarkers indicative of patient response to treatment has significant clinical implications in the stratification of patient treatment. Furthermore, understanding the molecular mechanisms underpinning tumour response and resistance to neo-CRT will contribute towards the identification of novel therapeutic targets for enhancing OAC sensitivity to CRT. MicroRNAs (miRNA/miR) function to regulate gene and protein expression and play a causal role in cancer development and progression. MiRNAs have also been identified as modulators of key cellular pathways associated with resistance to CRT. Here, to identify miRNAs associated with resistance to CRT, pre-treatment diagnostic biopsy specimens from patients with OAC were analysed using miRNA-profiling arrays. In pre-treatment biopsies miR-330-5p was the most downregulated miRNA in patients who subsequently failed to respond to neo-CRT. The role of miR-330 as a potential modulator of tumour response and sensitivity to CRT in OAC was further investigated in vitro. Through vector-based overexpression the E2F1/p-AKT survival pathway, as previously described, was confirmed as a target of miR-330 regulation. However, miR-330-mediated alterations to the E2F1/p-AKT pathway were insufficient to significantly alter cellular sensitivity to chemotherapy (cisplatin and 5-flurouracil). In contrast, silencing of miR-330-5p enhanced, albeit subtly, cellular resistance to clinically relevant doses of radiation. This study highlights the need for further investigation into the potential of miR-330-5p as a predictive biomarker of patient sensitivity to neo-CRT and as a novel therapeutic target for manipulating cellular sensitivity to neo-CRT in patients with OAC.
  • Treatment of Mycobacterium tuberculosis-Infected Macrophages with Poly(Lactic-Co-Glycolic Acid) Microparticles Drives NFκB and Autophagy Dependent Bacillary Killing.

    Lawlor, Ciaran; O'Connor, Gemma; O'Leary, Seonadh; Gallagher, Paul J; Cryan, Sally-Ann; Keane, Joseph; O'Sullivan, Mary P (PLoS ONE, 2016)
    The emergence of multiple-drug-resistant tuberculosis (MDR-TB) has pushed our available repertoire of anti-TB therapies to the limit of effectiveness. This has increased the urgency to develop novel treatment modalities, and inhalable microparticle (MP) formulations are a promising option to target the site of infection. We have engineered poly(lactic-co-glycolic acid) (PLGA) MPs which can carry a payload of anti-TB agents, and are successfully taken up by human alveolar macrophages. Even without a drug cargo, MPs can be potent immunogens; yet little is known about how they influence macrophage function in the setting of Mycobacterium tuberculosis (Mtb) infection. To address this issue we infected THP-1 macrophages with Mtb H37Ra or H37Rv and treated with MPs. In controlled experiments we saw a reproducible reduction in bacillary viability when THP-1 macrophages were treated with drug-free MPs. NFκB activity was increased in MP-treated macrophages, although cytokine secretion was unaltered. Confocal microscopy of immortalized murine bone marrow-derived macrophages expressing GFP-tagged LC3 demonstrated induction of autophagy. Inhibition of caspases did not influence the MP-induced restriction of bacillary growth, however, blockade of NFκB or autophagy with pharmacological inhibitors reversed this MP effect on macrophage function. These data support harnessing inhaled PLGA MP-drug delivery systems as an immunotherapeutic in addition to serving as a vehicle for targeted drug delivery. Such "added value" could be exploited in the generation of inhaled vaccines as well as inhaled MDR-TB therapeutics when used as an adjunct to existing treatments.
  • Impact of Fatigue in Rheumatic Diseases in the Work Environment: A Qualitative Study.

    Connolly, Deirdre; Fitzpatrick, Clodagh; O'Toole, Lynn; Doran, Michele; O'Shea, Finbar (MDPI AG, 2015-10-28)
    Fatigue is a symptom of arthritis that causes difficulty at work. An improved understanding of this symptom could assist its management in the work environment. The aim of this study was to explore people with rheumatic diseases' experiences of fatigue in work. A qualitative descriptive design was used with semi-structured interviews and a constant comparative method of data analysis. There were 18 participants, the majority of them female with Rheumatoid Arthritis (RA) and working full-time. Three themes were identified: "Impact of fatigue on work performance" with cognition, mood and physical abilities being the main difficulties reported. In the second theme "Disclosure at Work" participants discussed disclosing their disease to employers but reported a lack of understanding of fatigue from colleagues. The final theme "work-based fatigue management strategies" included cognitive strategies and energy management techniques, which were mainly self-taught. In this study, fatigue was reported to impact on many areas of work performance with limited understanding from colleagues and employers. Interventions from health professionals to assist with development of work-related self-management skills are required to assist with symptom management in the work place. Such interventions should include education to employers and colleagues on the nature of fatigue in Rheumatic diseases.
  • Hepatitis C in the era of direct-acting antivirals: real-world costs of untreated chronic hepatitis C; a cross-sectional study.

    Kieran, Jennifer Ann; Norris, Suzanne; O'Leary, Aisling; Walsh, Cathal; Merriman, Raphael; Houlihan, D; McCormick, P Aiden; McKiernan, Susan; Bergin, Colm; Barry, Michael (BioMed Central, 2015-10-26)
    Recent advances in Hepatitis C therapeutics offer the possibility of cure but will be expensive. The cost of treatment may be partially offset by the avoidance of advanced liver disease. We performed a micro-costing study of the ambulatory healthcare utilisation of patients with Hepatitis C supplemented with inpatient diagnosis related group costs.
  • A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study.

    Rawstron, A C; Fazi, C; Agathangelidis, A; Villamor, N; Letestu, R; Nomdedeu, J; Palacio, C; Stehlikova, O; Kreuzer, K-A; Liptrot, S; O'Brien, D; de Tute, R M; Marinov, I; Hauwel, M; Spacek, M; Dobber, J; Kater, A P; Gambell, P; Soosapilla, A; Lozanski, G; Brachtl, G; Lin, K; Boysen, J; Hanson, C; Jorgensen, J L; Stetler-Stevenson, M; Yuan, C; Broome, H E; Rassenti, L; Craig, F; Delgado, J; Moreno, C; Bosch, F; Egle, A; Doubek, M; Pospisilova, S; Mulligan, S; Westerman, D; Sanders, C M; Emerson, R; Robins, H S; Kirsch, I; Shanafelt, T; Pettitt, A; Kipps, T J; Wierda, W G; Cymbalista, F; Hallek, M; Hillmen, P; Montserrat, E; Ghia, P (2016-04)
    In chronic lymphocytic leukemia (CLL) the level of minimal residual disease (MRD) after therapy is an independent predictor of outcome. Given the increasing number of new agents being explored for CLL therapy, using MRD as a surrogate could greatly reduce the time necessary to assess their efficacy. In this European Research Initiative on CLL (ERIC) project we have identified and validated a flow-cytometric approach to reliably quantitate CLL cells to the level of 0.0010% (10(-5)). The assay comprises a core panel of six markers (i.e. CD19, CD20, CD5, CD43, CD79b and CD81) with a component specification independent of instrument and reagents, which can be locally re-validated using normal peripheral blood. This method is directly comparable to previous ERIC-designed assays and also provides a backbone for investigation of new markers. A parallel analysis of high-throughput sequencing using the ClonoSEQ assay showed good concordance with flow cytometry results at the 0.010% (10(-4)) level, the MRD threshold defined in the 2008 International Workshop on CLL guidelines, but it also provides good linearity to a detection limit of 1 in a million (10(-6)). The combination of both technologies would permit a highly sensitive approach to MRD detection while providing a reproducible and broadly accessible method to quantify residual disease and optimize treatment in CLL.
  • Opt-Out Panel Testing for HIV, Hepatitis B and Hepatitis C in an Urban Emergency Department: A Pilot Study.

    O'Connell, Sarah; Lillis, Darren; Cotter, Aoife; O'Dea, Siobhan; Tuite, Helen; Fleming, Catherine; Crowley, Brendan; Fitzgerald, Ian; Dalby, Linda; Barry, Helen; Shields, Darragh; Norris, Suzanne; Plunkett, Patrick K; Bergin, Colm (PLoS One, 2016)
    Studies suggest 2 per 1000 people in Dublin are living with HIV, the level above which universal screening is advised. We aimed to assess the feasibility and acceptability of a universal opt-out HIV, Hepatitis B and Hepatitis C testing programme for Emergency Department patients and to describe the incidence and prevalence of blood-borne viruses in this population.
  • Utilising magnetic resonance imaging as the gold-standard in management of suspected scaphoid fractures in the emergency department setting

    Ramasubbu, B; Mac Suibhne, E; El-Gammal, A; Sheehy, N; Shields, D (Irish Medical Journal, 2017-02)
    Scaphoid fractures are the most common carpal bone fracture. Up to 40% of scaphoid fractures can be missed at initial presentation and investigation. Follow-up plain film radiograph has overall poor sensitivity and reliability. MRI has been shown to have an almost 100% sensitivity and specificity and so is the gold standard in scaphoid fracture diagnosis. Additionally, early specialist involvement is recommended. We proposed that following a designated pathway, there would be no significant increase in MRI requests. Following implementation of a pathway for the management of suspected scaphoid fractures in St James’s Hospital in 2012 re-auditing demonstrated that management changed to either MRI directly after initial x-ray (16/145, 11%), MRI after second x-ray (9/28, 32%) or orthopaedic follow-up (19/28, 68%). The number of MRIs requested was consistent with our predictors of demand. Thus, our new protocol maximises diagnostics, cost effectiveness and quality of patient care.
  • Autumn Weather and Winter Increase in Cerebrovascular Disease Mortality

    McDonagh, R; Harbison, J (Irish Medical Journal, 2016-11)
    Mortality from cerebrovascular disease increases in winter but the cause is unclear. Ireland’s oceanic climate means that it infrequently experiences extremes of weather. We examined how weather patterns relate to stroke mortality in Ireland. Seasonal data for Sunshine (% of average), Rainfall (% of average) and Temperature (degrees Celsius above average) were collected for autumn (September-November) and winter (December-February) using official Irish Meteorological Office data. National cerebrovascular mortality data was obtained from Quarterly Vital Statistics. Excess winter deaths were calculated by subtracting (nadir) 3rd quarter mortality data from subsequent 1st quarter data. Data for 12 years were analysed, 2002-2014. Mean winter mortality excess was 24.7%. Winter mortality correlated with temperature (r=.60, p=0.04). Rise in winter mortality correlated strongly with the weather in the preceding autumn (Rainfall: r=-0.19 p=0.53, Temperature: r=-0.60, p=0.03, Sunshine, r=0.58, p=0.04). Winter cerebrovascular disease mortality appears higher following cool, sunny autum

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