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  • The characterization of an intestine-like genomic signature maintained during Barrett's-associated adenocarcinogenesis reveals an NR5A2-mediated promotion of cancer cell survival.

    Duggan, Shane P; Behan, Fiona M; Kirca, Murat; Zaheer, Abdul; McGarrigle, Sarah A; Reynolds, John V; Vaz, Gisela M F; Senge, Mathias O; Kelleher, Dermot; 1 Department of Medicine, Division of Gastroenterology, University of British Columbia, 2775 Laurel Street, Vancouver, British Columbia, Canada. 2 Life Science Institute, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada. 3 Department of Clinical Medicine, Institute of Molecular Medicine, Trinity College Dublin, St James' Hospital, Dublin, Ireland. 4 Department of Gastroenterology, St James' Hospital, Dublin, Ireland. 5 Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St James' Hospital, Dublin 8, Ireland. 6 Medicinal Chemistry, Trinity Translational Medicine Institute, Trinity College Dublin, the University of Dublin, St James' Hospital, Dublin 8, Ireland. (Nature Publishing Group, 2016-09-02)
    Barrett's oesophagus (BO), an intestinal-type metaplasia (IM), typically arising in conjunction with gastro-oesophageal reflux disease, is a prominent risk factor for the development of oesophageal adenocarcinoma (OAC). The molecular similarities between IM and normal intestinal tissues are ill-defined. Consequently, the contribution of intestine-enriched factors expressed within BO to oncogenesis is unclear. Herein, using transcriptomics we define the intestine-enriched genes expressed in meta-profiles of BO and OAC. Interestingly, 77% of the genes differentially expressed in a meta-profile of BO were similarly expressed in intestinal tissues. Furthermore, 85% of this intestine-like signature was maintained upon transition to OAC. Gene networking analysis of transcription factors within this signature revealed a network centred upon NR5A2, GATA6 and FOXA2, whose over-expression was determined in a cohort of BO and OAC patients. Simulated acid reflux was observed to induce the expression of both NR5A2 and GATA6. Using siRNA-mediated silencing and an NR5A2 antagonist we demonstrate that NR5A2-mediated cancer cell survival is facilitated through augmentation of GATA6 and anti-apoptotic factor BCL-XL levels. Abrogation of NR5A2-GATA6 expression in conjunction with BCL-XL co-silencing resulted in synergistically increased sensitivity to chemotherapeutics and photo-dynamic therapeutics. These findings characterize the intestine-like signature associated with IM which may have important consequences to adenocarcinogenesis.
  • Adolescent Substance Use ‘In Search of Solutions’

    Murray, Denis (Murray, Denis, 2018)
    Presentation to The School of Nursing and Midwifery, Trinity College Dublin as part of the Civic Engagement ‘Tell Me About’ Public lecture series.
  • Maximising Refractive Outcomes with an Extended Depth of Focus IOL.

    Power, Barry; Murphy, Rory; Leccisotti, Antonio; Moore, Tara; Power, William; O'Brien, Paul (The Open Ophthalmology Journal, 2018-01-01)
    To assess the impact of the magnitude of preoperative and postoperative corneal astigmatism on refractive outcomes in patients undergoing cataract surgery or lens exchange with an extended depth of focus intraocular lens. To compare visual outcomes of steep and temporal on-axis corneal incisions. Department of Ophthalmology, Blackrock Clinic, Dublin, Ireland. Prospective cohort analysis. Fifty-three consecutive adult patients (94 eyes) undergoing routine phacoemulsification with Symfony IOL implantation were analysed. Exclusion criteria: targets for mini-monovision, incomplete data, other ocular pathology. Data were prospectively collected on pre- and postoperative refraction, keratometry, distance vision, near vision, surgical wound site and Surgically Induced Astigmatism (SIA).
  • Maternal body mass index and the prevalence of spontaneous and elective preterm deliveries in an Irish obstetric population: a retrospective cohort study.

    Vinturache, Angela; McKeating, Aoife; Daly, Niamh; Sheehan, Sharon; Turner, Michael; Centre for Human Reproduction, University College Dublin, Coombe Women and Infants University Hospital, Dublin, Ireland (BMJ, 2017-10-15)
    To estimate the association between maternal body mass index (BMI) and risk of spontaneous preterm delivery (sPTD) and elective preterm delivery (ePTD) in singleton and multiple pregnancies. Retrospective cohort study. Electronic records of all deliveries from 2009 through 2013 in a tertiary university hospital were abstracted for demographic and obstetrical information. A total of 38 528 deliveries were included. Participants with missing data were excluded from the study. BMI was calculated from the measurement of height and weight at the first prenatal visit and categorised. Sonographic confirmation of gestational age was standard.
  • Intramuscular oxytocin versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery (LabOR trial): study protocol for a randomised controlled trial.

    Adnan, Nita; Boland, Fiona; Murphy, Deirdre J; Academic Department of Obstetrics and Gynaecology, Trinity College, University of Dublin & Coombe Women & Infants University Hospital, Dublin 8, Ireland/ Department of General Practice, Royal College of Surgeons in Ireland, Dublin 2, Ireland (Biomed Central, 2017-11-15)
    Primary postpartum haemorrhage (PPH) is one of the leading causes of maternal morbidity and mortality worldwide. The most common cause of primary PPH is uterine atony. Atonic PPH rates are increasing in developed countries despite routine active management of the third stage of labour. In less-developed countries, primary PPH remains the leading cause of maternal death. Although the value of routine oxytocics in the third stage of labour has been well established, there is inconsistent practice in the choice of agent and route of administration. Oxytocin is the preferred agent because it has fewer side effects than other uterotonics with similar efficacy. It can be given intravenously or intramuscularly; however, to date, the most effective route of administering oxytocin has not been established. A double-blind randomised controlled trial is planned. The aim of the study is to compare the effects of an intramuscular bolus of oxytocin (10 IU in 1 mL) and placebo intravenous injection (1 mL 0.9% saline given slowly) with an intravenous bolus of oxytocin (10 IU in 1 mL given slowly over 1 min) and placebo intramuscular injection (1 mL 0.9% saline) at vaginal delivery. The study will recruit 1000 women at term (>36 weeks) with singleton pregnancies who are aiming for a vaginal delivery. The primary outcome will be PPH (measured blood loss ≥ 500 mL). A study involving 1000 women will have 80% power at the 5% two-sided alpha level, to detect differences in the proportion of patients with measured blood loss > 500 ml of 10% vs 5%. Given the increasing trends of atonic PPH it is both important and timely that we evaluate the most effective route of oxytocin administration for the management of the third stage of labour. To date, there has been limited research comparing the efficacy of intramuscular oxytocin vs intravenous oxytocin for the third stage of labour. ISRCTN Registry, ISRCTN14718882 . Registered on 4 January 2016. Pilot commenced 12.12.2015; trial commenced 04.01.2016. The protocol (Ref 012012) was approved by the National Maternity Hospital Research Ethics Committee on 10.06.2015 and the Research Ethics Committee of the Coombe Women & Infants University Hospital (Ref 26-2015) on 09.12.2015.
  • Children's complex care needs: a systematic concept analysis of multidisciplinary language.

    Brenner, Maria; Kidston, Claire; Hilliard, Carol; Coyne, Imelda; Eustace-Cook, Jessica; Doyle, Carmel; Begley, Thelma; Barrett, Michael J; School of Nursing & Midwifery, Trinity College Dublin (Springer, 2018-11-01)
    Complex care in the arena of child health is a growing phenomenon. Although considerable research is taking place, there remains limited understanding and agreement on the concept of complex care needs (CCNs), with potential for ambiguity. We conducted a systematic concept analysis of the attributes, antecedents, and consequences of children's CCNs from a multidisciplinary perspective. Our data sources included PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO. Inclusion criteria included publications in peer-reviewed journals between January 1990 and December 2017, written in the English language. One hundred and forty articles were included. We found that children's CCNs refer to multidimensional health and social care needs, in the presence of a recognized medical condition or where there is no unifying diagnosis.Conclusion: Children's CCNs are individual and contextualized, are continuing and dynamic, and are present across a range of settings, impacted by family and healthcare structures. There remain extensive challenges to caring for these children and their families, precluding the possibility that any one profession can possess the requisite knowledge or scope to singularly provide high-quality competent care. What is Known: • Complex care is a growing phenomenon and population prevalence figures show that there is an increasing number of children with complex care needs (CCNs). However, the concept has not been systematically analyzed before, leaving it generally ill-defined and at times confusing. What is New: • This is the first time this concept has been systematically analyzed and this analysis provides a much-needed theoretical framework for understanding the multidimensional nature of CCNs in children. • Children's CCNs refer to multidimensional health and social care needs in the presence of a recognized medical condition or where there is no unifying diagnosis. They are individual and contextualized, are continuing and dynamic, and are present across a range of settings, impacted by family and healthcare structures. It is clear that the very nature of CCNs precludes the possibility that any one profession or discipline can possess the requisite knowledge or scope for high-quality competent care for this population.
  • Variations in Abnormal Nipple Discharge Management in Women- a Systematic Review and Meta-analysis

    Leong, Alison; Johnston, Alison; Sugrue, Michael (Journal of surgery, 2018-07)
    Nipple discharge accounts for 5% of referrals to breast units; breast cancer in image negative nipple discharge patients varies from 0 to 21%. This systematic review and meta-analysis determined variability in breast cancer rates in nipple discharge patients, diagnostic accuracy of modalities and surgery rates. An ethically approved meta-analysis was conducted using databases PubMed, EMBASE, and Cochrane Library from January 2000 to July 2015. For the breast cancer rates’ review, studies were excluded if no clinical follow-up data was available. For the diagnostic accuracy meta-analysis, studies were excluded if there was no reference standard, or the number of true and false positives and negatives were not known. Pooled sensitivities were determined using Mantel-Haenszel method. For the surgery rates’ review, only studies with consecutive nipple discharge patients were included. Average risk of having a breast cancer is 10.2% in nipple discharge patients. Most studies reported an age threshold of 50 above which breast cancer risk greatly increases. Pooled sensitivities of ultrasound, mammogram, mammogram and ultrasound, breast MRI, conventional galactography, smear cytology, ductal lavage cytology and ductoscopy were 0.64, 0.34, 0.65, 0.81, 0.75, 0.37, 0.49 and 0.82 respectively. Average surgery rate was 43.4%. Malignancy rate of 10.2% indicates the need to continue surgery, especially for patients aged over 50. Patients below 50, in the absence of risk factors such as family history, can be managed conservatively with close follow up.
  • Growth Patterns in the Irish Pyridoxine Nonresponsive Homocystinuria Population and the Influence of Metabolic Control and Protein Intake.

    Purcell, Orla; Coughlan, Aoife; Grant, Tim; McNulty, Jenny; Clark, Anne; Deverell, Deirdre; Mayne, Philip; Hughes, Joanne; Monavari, Ahmad; Knerr, Ina; Crushell, Ellen; Temple St (2017-01-01)
    A low methionine diet is the mainstay of treatment for pyridoxine nonresponsive homocystinuria (HCU). There are various guidelines for recommended protein intakes for HCU and clinical practice varies. Poor growth has been associated with low cystine levels. This retrospective review of 48 Irish pyridoxine nonresponsive HCU patients assessed weight, height, body mass index (BMI), protein intake, and metabolic control up to 18 years at nine set time points. Patients diagnosed through newborn screening (NBS) were compared to late diagnosed (LD) patients. At 18 years the LD group
  • Placental FKBP51 mediates a link between second trimester maternal anxiety and birthweight in female infants.

    Togher, Katie L; O'Keeffe, Gerard W; Khashan, Ali S; Clarke, Gerard; Kenny, Louise C; Cork University Maternity Hospital and University College Cork (Scientific Reports, 2018-10-11)
    Prenatal distress is associated with adverse outcomes in affected offspring. Alterations in placental glucocorticoid signalling and subsequent foetal overexposure to glucocorticoids have been implicated as an underlying mechanism. Infant sex is emerging as an important factor in disease susceptibility. This study aimed to examine the effects of maternal distress across pregnancy on birth outcomes and placental glucocorticoid genes in a sex-dependent manner. Participants completed psychological distress questionnaires throughout pregnancy. Placental HSD11B2, NR3C1 and FKBP51 were analysed by real time PCR and cortisol was measured in new-born hair. Second trimester stress was negatively correlated with birthweight in males and positively correlated with placental NR3C1 mRNA in females. Second trimester anxiety was negatively correlated with birthweight and placental FKBP51 mRNA in females. In mediation analysis, placental FKBP51 mRNA expression was found to mediate the link between prenatal anxiety and birthweight. New-born cortisol was negatively correlated with second trimester anxiety and positively correlated with female placental FKBP51 mRNA levels. Again, FKBP51 mRNA was found to mediate the link between anxiety and new-born cortisol. These results highlight a role for FKBP51 in the placental response to prenatal distress in females. The precise role that placental FKBP51 has in foetal and infant development has not been extensively studied and warrants further investigations.
  • "Say BOO to the FLU!" Introduction of the Seasonal Influenza Peer Vaccination Programme in the Emergency Department and AMAU.

    Donaghy, Lisa; Martin, Patrick; Connolly Hospital Blanchardstown (2018-07-01)
    The Seasonal Influenza Peer Vaccination Programme was developed by the Republic of Ireland Health Service Executive (HSE)1 with the aim of increasing the number of health care workers receiving annual flu vaccinations. Supporting these efforts, various studies illustrated that increasing health care staff vaccination rates decreased patient illness and death,2 while other research reported a 40% reduction of influenza-related deaths in hospitals with higher rates of health care workers' influenza vaccinations.3 Flu vaccination recommendations from The WorldHealthOrganization (WHO) include a target uptake of 75% in health care staff and people age 65 and older.3 In accordance with HSE national guidelines that health care organizations achieve and/or surpass the minimum threshold goal of 40% of employees receiving the flu vaccine,4 and recognizing that Peer-to-Peer Influenza Vaccination Programmes are an essential aspect of the overall infection prevention and control arrangements in our health care setting, Connolly Hospital In Dublin, Ireland, initiated the Peer Vaccination Programme in the Emergency Department and Acute Medical Assessment Unit (AMAU) during the 2016–2017 flu season. The challenges facing successful ED and AMAU programme implementation included the large volume of interdisciplinary staff serving theED area, a vast cohort of undifferentiated complex patients at risk for increased complications if exposed to influenza, and an elevated risk of exposure to the influenza virus for all members of the health care team. Similar to programs in other countries, the Peer-to-Peer Vaccination Programme vaccinates health care workers against the influenza viruses identified as those most likely to circulate in the upcoming season.5 Although recognizing that frontline staff have a duty of care to protect their patients and colleagues, receiving the flu vaccine is not a mandatory requirement for health care worker employment in Ireland.
  • The Case for Shared Medical and Psychiatric Units: Are They Needed and How They Could Run?

    Duffy, R.M; Sadlier, M; Van Der Ploeg, A.H.; Sheehan, J; 1. Mater Misericordiae University Hospital . 2. Academic Centre of Psychiatry, University of Groningen (Irish Medical Journal, 2018-10)
    A diagnosis of major mental illness is associated with a 15-20 year reduction in life expectancy. Individuals with mental illness face many difficulties accessing and receiving healthcare, many of these barriers exist in secondary care. On medical and surgical wards, the majority of mental healthcare is delivered by consultation liaison services. Hospital based psychiatry is increasingly important; well designed services are often cost-effective and can reduce patient’s length of stay. Some individual’s care needs, however, exceed the capacity of such a service. There is a significant unmet need for individuals with severe co-morbid mental and physical illness, due to their increased lengths of stay, costs and readmission rate. In these cases ‘both medical and psychiatric safety features form a prerequisite for the physical settings’ 4. This paper examines the need for shared care units (SCU), with additional mental health input. A Vision for Change proposes one adult liaison mental health services for 300,000 people and a national 6-10 bed neuropsychiatry unit. While the proposed neuropsychiatry unit does not currently exist it would only address a small proportion of the individuals who could benefit from a SCU. In Ireland there are currently just over 10,000 acute inpatient beds. Overall 52.5 people per 100,000 require inpatients mental health services. Based on these numbers there is a need for 5 inpatient beds nationally where medical and psychiatric needs can be addressed simultaneously. This calculation however falsely assumes no association between physical and mental health morbidity. In reality a bidirectional association is well established. Psychological morbidity is higher in medical inpatients. A study of general medical and trauma orthopedic admissions, showed that 64% of those over 70 had significant psychiatric morbidity including 8% with delusions and 6% with hallucinations. Patients with major mental illnesses have increased levels of mortality, even in highly income countries greatly reduced life expentancy Kishi and Kanthol suggest that one percent of patients admitted to general hospital would benefit from a SCU4. Compounding this association between physical and psychological illness is the fact that Ireland’s population is aging, older patients have higher rates of inpatient care for both physical and mental health reasons. A review of four studies of such wards demonstrated that SCUs reduce psychiatric symptoms, shorten in length of stay, improve functional outcomes and a decrease the need for long-term care. A medical and mental health unit for older individuals with delirium and dementia has been trialed in the UK with initially favorable and cost effective results11. We identify three cohorts of patients who may benefit from this service. The interventions such a ward could deliver are examined and some of the potential practical considerations are discussed. Key potential benefits that this shared model could provide are highlighted.
  • Merkel Cell Carcinoma: A Case Series

    Zafar, S.A; O.M Ahmed, O.M; Boland, M.R; Aucharaz, N; Lal, A (Irish Medical Journal, 2018-10)
    Merkel cell carcinoma (MCC) is a rare cutaneous tumour that is clinically aggressive with a high local, regional, and distant metastatic potential.
  • Sarcomatoid Carcinoma of the Prostate Presenting in a 44 Year Old

    Conroy, M; Greally, M; MacEneaney, O; O’Keane, C; McCaffrey, J; Mater Misericordiae University Hospital, Dublin (Irish Medical Journal, 2018-10)
    We present the case of a 44-year-old man diagnosed with metastatic sarcomatoid carcinoma of the prostate. The pathogenesis and optimal treatment of this rare and aggressive subtype of prostate cancer are not fully clear. The patient was managed using a multimodality approach of chemotherapy, hormonal blockade and radiation therapy, with palliative intent.
  • IgG4 Related Disease, A Case of Large Vessel Vasculitis

    O’Sullivan, A; Ghazi Al Qatari, S; Murphy, G; Cork University Hospital (Irish Medical Journal, 2018-10)
    This report describes a case of large vessel vasculitis highlighting diagnostic and therapeutic challenges. It describes the use of the B cell depleting agent Rituximab in this setting. This is the case of a 50 year old lady with bipolar disorder presenting with lower limb pain.
  • Ankylosing Spondylitis Response to TNF Inhibition Is Gender Specific: A 6-Year Cohort Study

    Murray, C; Fearon, C; Dockery, M; Moran, D; Heffernan, E; Fitzgerald, O; Veale, D.J; Harty, L; St. Vincent's University Hospital (Irish Medical Journal, 2018-10)
    Recent studies have suggested gender-specific differences with respect to both baseline disease activity and severity in ankylosing spondylitis (AS). Tumour necrosis factor inhibitors (TNFi) have shown significant benefit in AS but there may be gender-specific differences regarding responses to TNFi therapy.
  • Point of Care Echocardiography in an Irish Critical Care Unit

    Kuriakose, D; O’Mahony, R; Rooplalsingh, R; McCanny, P; Colreavy, F; 1. Our Lady of Lourdes Hospital, Drogheda 2. Connolly Hospital, Blanchardstown, Co. Dublin 3. The Prince Charles Hospital, Rode Road, Chermside, Aus 4. Liverpool Hospital, Liverpool, New South Wales, Aus 5. Mater Misercordiae University Hospital, Dublin (Irish Medical Journal, 2018-10)
    We sought to evaluate the clinical impact of a 6 month transthoracic echocardiography (TTE) teaching programme in a critical care unit.
  • Coming of Age in Ireland: the Twilight Zone!

    Power, B.D; Stewart, P; Stone, G; O’Reilly, P; Costigan, C; O’Gorman, C; Murphy, A.M; University Hospital Limerick (Irish Medical Journal, 2018-10)
    To describe the healthcare needs of adolescent patients inhabiting the ‘seventh age of childhood’ in our region with a view towards future workforce and infrastructure planning.
  • Report on the death of patients in whom CPE had been detected

    Spencer, Robert C.
    Following the first Irish outbreak of Carbapenemase Producing Enterobacteriaceae [CPE] at UHL in 2011, there has been an ongoing increased detection of CPE in the UL Hospitals Group (ULHG) with multiple associated outbreaks. An extensive screening programme is currently in place; in critical care and for newly admitted patients should they fulfil specific screening criteria [ULHG Guidelines for the Prevention, Control & Management of CRE including KPC. Document: QPRS-IPCH-10 Approved January 2016].
  • Safety of Adalimumab Dosed Every Week and Every Other Week: Focus on Patients with Hidradenitis Suppurativa or Psoriasis.

    Ryan, Caitriona; Sobell, Jeffrey M; Leonardi, Craig L; Lynde, Charles W; Karunaratne, Mahinda; Valdecantos, Wendell C; Hendrickson, Barbara A (American Journal of Clinical Dermatology, 2018-06-01)
    Adalimumab is approved for the treatment of hidradenitis suppurativa (HS), plaque psoriasis, and other inflammatory conditions. Our objective was to examine the safety of adalimumab administered every other week (EOW) and every week (EW) in patients with HS and psoriasis and to investigate informative data from non-dermatologic indications. The safety of adalimumab 40-mg EOW versus EW dosing was examined during placebo-controlled and open-label study periods in patients with HS (three studies), psoriasis (two studies), Crohn's disease (six studies), ulcerative colitis (three studies), and rheumatoid arthritis (one study). No new safety risks or increased rates of particular adverse events (AEs) were identified with EW dosing. In patients with HS or psoriasis, the overall safety of adalimumab 40-mg EOW and EW was generally comparable. In studies of adalimumab for non-dermatologic indications, including Crohn's disease, ulcerative colitis, and rheumatoid arthritis, the overall AE rates were similar for EW and EOW dosing.
  • Caffeine Treatment for Apnea of Prematurity and the Influence on Dose-Dependent Postnatal Weight Gain Observed Over 15 Years.

    Philip, Roy K; Ismail, Abu; Murphy, Bernadette; Mirza, Adnan; Quinn, Collette; Dunworth, Margo; University Hospital Limerick (Journal of Caffeine and Adenosine Research, 2018-09-01)
    To analyze the influence on weight gain of infants exposed to two dosage regimens of oral caffeine citrate (CC) for apnea of prematurity.

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