• Gene expression profiling in cervical cancer: identification of novel markers for disease diagnosis and therapy.

      Martin, Cara M; Astbury, Katharine; McEvoy, Lynda; O'Toole, Sharon; Sheils, Orla; O'Leary, John J; Department of Pathology, Coombe Women's Hospital, Dublin, Ireland. (2012-02-01)
      Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus is the single most important etiological agent in cervical cancer. HPV contributes to neoplastic progression through the action of two viral oncoproteins E6 and E7, which interfere with critical cell cycle pathways, p53, and retinoblastoma. However, evidence suggests that HPV infection alone is insufficient to induce malignant changes and other host genetic variations are important in the development of cervical cancer. Advances in molecular biology and high throughput gene expression profiling technologies have heralded a new era in biomarker discovery and identification of molecular targets related to carcinogenesis. These advancements have improved our understanding of carcinogenesis and will facilitate screening, early detection, management, and personalised targeted therapy. In this chapter, we have described the use of high density microarrays to assess gene expression profiles in cervical cancer. Using this approach we have identified a number of novel genes which are differentially expressed in cervical cancer, including several genes involved in cell cycle regulation. These include p16ink4a, MCM 3 and 5, CDC6, Geminin, Cyclins A-D, TOPO2A, CDCA1, and BIRC5. We have validated expression of mRNA using real-time PCR and protein by immunohistochemistry.
    • Hepatitis C: is there a case for universal screening in pregnancy?

      Martyn, F; Phelan, O; O'Connell, M; Department of Obstetrics & Gynaecology, Coombe Women & Infant's University, Hospital, Dolphin's Barn, Dublin 8. f_martyn@yahoo.com (2012-02-01)
      Hepatitis C (HCV) is not routinely screened for antenatally in all maternity hospitals. Most hospitals adopt a policy of targeted screening. The policy in the Coombe Women and Infants University Hospital in Dublin changed from targeted screening in 2006 to universal screening in 2007. We audited the two consecutive years. The prevalence of HCV in our antenatal population was 1.4% for 2006 (67/4666) when targeted screening applied and in 2007--0.71% (66/9222) when universal screening came into affect. One woman in 2007 would not have been detected by targeted screening--1.49% (1/67). Fifty five percent (37/67) of women were HCV-RNA positive in 2006 and 57.5% (38/66) were positive in 2007. We conclude that there were similar detection rates for HCV in 2006 and 2007 and that universal screening is not required if inclusive criteria for selective screening are employed but is of use in research context.
    • Hepatitis C: is there a case for universal screening in pregnancy?

      Martyn, F; Phelan, O; O'Connell, M; Department of Obstetrics & Gynaecology, Coombe Women & Infant's University Hospital, Dolphin's Barn, Dublin 8. f_martyn@yahoo.com (2011-05)
      Hepatitis C (HCV) is not routinely screened for antenatally in all maternity hospitals. Most hospitals adopt a policy of targeted screening. The policy in the Coombe Women and Infants University Hospital in Dublin changed from targeted screening in 2006 to universal screening in 2007. We audited the two consecutive years. The prevalence of HCV in our antenatal population was 1.4% for 2006 (67/4666) when targeted screening applied and in 2007--0.71% (66/9222) when universal screening came into affect. One woman in 2007 would not have been detected by targeted screening--1.49% (1/67). Fifty five percent (37/67) of women were HCV-RNA positive in 2006 and 57.5% (38/66) were positive in 2007. We conclude that there were similar detection rates for HCV in 2006 and 2007 and that universal screening is not required if inclusive criteria for selective screening are employed but is of use in research context.
    • How many joints does the 5th toe have? A review of 606 patients of 655 foot radiographs.

      Moulton, Lawrence Stephen; Prasad, Seema; Lamb, Robert G; Sirikonda, Siva P; Department of Orthopaedics, Royal United Hospital Bath NHS Trust, Coombe Park, Bath, United Kingdom. Lawrence.moulton@doctors.net.uk (Elsevier, 2012-12)
      It is a common understanding that the fifth toe has three bones with two interphalangeal joints. However, our experience shows that a significant number have only two phalanges with one interphalangeal joint.
    • How Much Greater is Obstetric Intervention in Women with Medical Disorders in Pregnancy When Compared to the General Population?

      Keane, R.; Manning, C.; Lynch, C.; Regan, C.; Byrne, B. (Irish Medical Journal, 2019-10)
      The purpose of this study was to compare obstetric and neonatal outcomes between women attending a specialised maternal medicine service and the general obstetric population.
    • Human papillomavirus vaccination in the prevention of cervical neoplasia.

      Astbury, Katharine; Turner, Michael J; Department of Obstetrics and Gynaecology, Coombe Women's Hospital, Dublin,, Ireland. kathastbury@gmail.com (2012-02-01)
      Cervical cancer remains a major cause of morbidity and mortality for women worldwide. Although the introduction of comprehensive screening programs has reduced the disease incidence in developed countries, it remains a major problem in the developing world. The recent licensing of 2 vaccines against human papillomavirus (HPV) type 16 and HPV-18, the viruses responsible for 70% of cervical cancer cases, offers the hope of disease prevention. In this article, we review the role of HPV in the etiology of cervical cancer and the evidence to support the introduction of vaccination programs in young women and discuss the potential obstacles to widespread vaccination. In addition, we discuss the issues that remain to be elucidated, including the potential need for booster doses of the vaccine and the role of concomitant vaccination in men.
    • Identifying novel hypoxia-associated markers of chemoresistance in ovarian cancer.

      McEvoy, Lynda M; O'Toole, Sharon A; Spillane, Cathy D; Martin, Cara M; Gallagher, Michael F; Stordal, Britta; Blackshields, Gordon; Sheils, Orla; O'Leary, John J (Springer, 2015)
      Ovarian cancer is associated with poor long-term survival due to late diagnosis and development of chemoresistance. Tumour hypoxia is associated with many features of tumour aggressiveness including increased cellular proliferation, inhibition of apoptosis, increased invasion and metastasis, and chemoresistance, mostly mediated through hypoxia-inducible factor (HIF)-1α. While HIF-1α has been associated with platinum resistance in a variety of cancers, including ovarian, relatively little is known about the importance of the duration of hypoxia. Similarly, the gene pathways activated in ovarian cancer which cause chemoresistance as a result of hypoxia are poorly understood. This study aimed to firstly investigate the effect of hypoxia duration on resistance to cisplatin in an ovarian cancer chemoresistance cell line model and to identify genes whose expression was associated with hypoxia-induced chemoresistance.
    • Impact of a personal learning plan supported by an induction meeting on academic performance in undergraduate Obstetrics and Gynaecology: a cluster randomised controlled trial

      Deane, Richard P; Murphy, Deirdre J; Department of Obstetrics & Gynaecology, Trinity College (BioMed Central, 2015)
      BACKGROUND: A personal learning plan (PLP) is an approach to assist medical students maximise their learning experience within clinical rotations. The aim of this study was to investigate whether medical students who created a PLP supported by an induction meeting had an improved academic performance within an undergraduate clinical rotation. METHODS: A cluster randomised controlled study was conducted over a full academic year (2012/13). The intervention was the creation of a PLP by medical students supported by an individual 'one-to-one' induction meeting between each student and a faculty member. Randomisation was by unit of rotation in which students completed the program. There were 2 clusters in the intervention group (n = 71 students) and 2 clusters in the control group (n = 72 students). Primary outcome was the overall examination score. Secondary outcomes were student attendance and student evaluation. RESULTS: There was no difference in overall examination score between the intervention group and control group (mean score 56.3 ± 4.8% versus 56.7 ± 5.6%, p = 0.64). The majority of students in the intervention group (n = 51/71, 85%) reported that the PLP and induction meeting enhanced their learning experience. Attendance at the induction meeting was identified as a key element. CONCLUSIONS: The creation of a PLP supported by an induction meeting was rated highly by students as an approach to enhance their learning experience but did not result in an improved academic performance. Further research is required to establish the role of an interim or exit meeting.
    • The impact of new national guidelines on screening for gestational Diabetes Mellitus

      Ali, FM; Farah, N; O’Dwyer, V; O’Connor, C; Kennelly, MM; Turner, MJ (Irish Medical Journal, 2013-02)
      Gestational diabetes mellitus (GDM) has important maternal and fetal implications. In 2010, the Health Service Executive published guidelines on GDM. We examined the impact of the new guidelines in a large maternity unit. In January 2011, the hospital replaced the 100g Oral Glucose Tolerance Test (OGTT) with the new 75g OGTT. We compared the first 6 months of 2011 with the first 6 months of 2010. The new guidelines were associated with a 22% increase in women screened from 1375 in 2010 to 1679 in 2011 (p<0.001). Of the women screened, the number diagnosed with GDM increased from 10.1% (n=139) to 13.2% (n=221) (p<0.001).The combination of increased screening and a more sensitive OGTT resulted in the number of women diagnosed with GDM increasing 59% from 139 to 221 (p=0.02).This large increase has important resource implications but, if clinical outcomes are improved, there should be a decrease in long-term costs.
    • The impact of new national guidelines on screening for gestational diabetes mellitus.

      Ali, F M; Farah, N; O'Dwyer, V; O'Connor, C; Kennelly, M M; Turner, M J (2013-02)
      Gestational diabetes mellitus (GDM) has important maternal and fetal implications. In 2010, the Health Service Executive published guidelines on GDM. We examined the impact of the new guidelines in a large maternity unit. In January 2011, the hospital replaced the 100 g Oral Glucose Tolerance Test (OGTT) with the new 75 g OGTT. We compared the first 6 months of 2011 with the first 6 months of 2010. The new guidelines were associated with a 22% increase in women screened from 1375 in 2010 to 1679 in 2011 (p < 0.001). Of the women screened, the number diagnosed with GDM increased from 10.1% (n=139) to 13.2% (n=221) (p<0.001).The combination of increased screening and a more sensitive OGTT resulted in the number of women diagnosed with GDM increasing 59% from 139 to 221 (p = 0.02).This large increase has important resource implications but, if clinical outcomes are improved, there should be a decrease in long-term costs.
    • Implementation of guidelines on oxytocin use at caesarean section: a survey of practice in Great Britain and Ireland.

      Sheehan, Sharon R; Wedisinghe, Lilantha; Macleod, Maureen; Murphy, Deirdre J; Academic Department of Obstetrics & Gynaecology, Coombe Women and Infants, University Hospital & Trinity College, University of Dublin, Dublin 8, Ireland., sharon.sheehan@tcd.ie (2012-02-01)
      OBJECTIVE: Caesarean section is one of the most commonly performed major operations on women worldwide. Operative morbidity includes haemorrhage, anaemia, blood transfusion and in severe cases, maternal death. Various clinical guidelines address oxytocin use at the time of caesarean section. We previously reported wide variation in practice amongst clinicians in the United Kingdom in the use of oxytocin at caesarean section. The aim of this current study was to determine whether the variation in approach is universal across the individual countries of Great Britain and Ireland and whether this reflects differences in interpretation and implementation of clinical practice guidelines. STUDY DESIGN: We conducted a survey of practice in the five individual countries of Great Britain and Ireland. A postal questionnaire was sent to all lead consultant obstetricians and anaesthetists with responsibility for the labour ward. We explored the use of oxytocin bolus and infusion, the measurement of blood loss at caesarean section and the rates of major haemorrhage. Existing clinical guidelines from the National Institute for Clinical Excellence (NICE), the Royal College of Obstetricians and Gynaecologists (RCOG) and ALSO (Advanced Life Support in Obstetrics) were used to benchmark reported practice against recommended practice for the management of blood loss at caesarean section. RESULTS: The response rate was 82% (391 respondents). Use of a 5 IU oxytocin bolus was reported by 346 respondents (85-95% for individual countries). In some countries, up to 14% used a 10 IU oxytocin bolus despite recommendations against this. Routine use of an oxytocin infusion varied greatly between countries (11% lowest-55% highest). Marked variations in choice of oxytocin regimens were noted with inconsistencies in the country-specific recommendations, e.g. NICE (which covers England and Wales) recommends a 30 IU oxytocin infusion over 4h, but only 122 clinicians (40%) used this. CONCLUSIONS: Clinicians' approach to the use of oxytocin at the time of caesarean delivery varies between countries. Even in countries with on-site visits to ensure guideline implementation (e.g. Clinical Negligence Scheme for Trusts in England), deviations from guideline recommendations exist. These variations may reflect a lack of robust evidence and the need for future research in this area.
    • The influence of maternal body composition on birth weight.

      Farah, Nadine; Stuart, Bernard; Donnelly, Valerie; Kennelly, Mairead M; Turner, Michael J; UCD Centre for Human Reproduction, Coombe Women and Infants University Hospital, , Dublin, Ireland. nadine.farah@ucd.ie (2012-02-01)
      OBJECTIVE: To identify the maternal body composition parameters that independently influence birth weight. STUDY DESIGN: A longitudinal prospective observational study in a large university teaching hospital. One hundred and eighty-four non-diabetic caucasian women with a singleton pregnancy were studied. In early pregnancy maternal weight and height were measured digitally in a standardised way and the body mass index (BMI) was calculated. At 28 and 37 weeks' gestation maternal body composition was assessed using segmental multifrequency bioelectrical impedance analysis. At delivery the baby was weighed and the clinical details were recorded. RESULTS: Of the women studied, 29.2% were overweight and 34.8% were obese. Birth weight did not correlate with maternal weight or BMI in early pregnancy. Birth weight correlated with gestational weight gain (GWG) before the third trimester (r=0.163, p=0.027), but not with GWG in the third trimester. Birth weight correlated with maternal fat-free mass, and not fat mass at 28 and 37 weeks gestation. Birth weight did not correlate with increases in maternal fat and fat-free masses between 28 and 37 weeks. CONCLUSIONS: Contrary to previous reports, we found that early pregnancy maternal BMI in a non-diabetic population does not influence birth weight. Interestingly, it was the GWG before the third trimester and not the GWG in the third trimester that influenced birth weight. Our findings have implications for the design of future intervention studies aimed at optimising gestational weight gain and birth weight. CONDENSATION: Maternal fat-free mass and gestational weight gain both influence birth weight.
    • 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.
    • Intramuscular versus intravenous oxytocin to prevent postpartum haemorrhage at vaginal delivery: randomised controlled trial.

      Adnan, Nita; Conlan-Trant, Rebecca; McCormick, Ciara; Boland, Fiona; Murphy, Deirdre J (BMJ, 2018-09-04)
      To determine whether intravenous oxytocin is more effective than intramuscular oxytocin at preventing postpartum haemorrhage at vaginal delivery. Double blind placebo controlled randomised trial. University affiliated maternity unit in the Republic of Ireland. 1075 women aged 18 years or older, at term with a singleton pregnancy who were aiming for a vaginal delivery with an actively managed third stage of labour.
    • The Irish Maternity Early Warning System (IMEWS).

      Maguire, P J; O'Higgins, A; Power, K; Turner, M J (Irish Medical Journal, 2014-11)
      In the acute hospital setting, the use of early warning scores (EWS) to monitor vital signs (including heart rate, respiratory rate [RR], blood pressure and temperature) has been shown to be beneficial in the early diagnosis and prompt initiation of treatment in adults with a critical illness 1 . This led to the development of the National Early Warning Score (NEWS) in Ireland by the Health Services Executiveâ s (HSE) Acute Medicine Clinical Care Programme. The NEWS was the first guideline endorsed by the National Clinical Effectiveness Committee (NCEC) and was launched by the Minister of Health Dr James Reilly in 2013. The implementation of NEWS is now mandatory in all acute hospitals. However, NEWS is not suitable for use in pregnancy because a womanâ s vital signs change physiologically from early in pregnancy. National reports in Ireland and the United Kingdom (UK) on maternal mortality have led to recommendations that a modified obstetric EWS be introduced 2,3 . In Ireland, these recommendations have been further supported by separate investigations in 2008 and 2013 on two maternal deaths from sepsis 4,5 .
    • Is birth weight the major confounding factor in the study of gestational weight gain?: an observational cohort study.

      O'Higgins, Amy C; Doolan, Anne; McCartan, Thomas; Mullaney, Laura; O'Connor, Clare; Turner, Michael J (BMC Pregnancy & Childbirth, 2018-06-07)
      Much interest has been focussed on both maternal obesity and gestational weight gain (GWG), particularly on their role in influencing birth weight (BW). Several large reviews have reported that excessive GWG is associated with an increase in BW Women were enrolled at their convenience before 18 weeks gestation. Height and weight were measured accurately at the first antenatal visit and BMI calculated. Maternal weight was measured again after 37 weeks gestation. The weight of the baby was measured at birth. Relationships were tested using linear regression analysis, chi-squared tests and t-tests as appropriate. Of the 522 women studied, the mean BMI was 25.3 kg/m The positive correlation between GWG in pregnancy and BW can be accounted for by the contribution of fetal weight to GWG antenatally without a contribution from increased maternal adiposity. There was a wide range of BW irrespective of the degree of GWG and obese women had a lower GWG than non-obese women. These findings help explain why Randomized Controlled Trials (RCTs) designed to reduce GWG have failed to decrease BW and suggest there is no causative link between excessive GWG and increased BW.
    • Is point of care testing in Irish hospitals ready for the laboratory modernisation process? An audit against the current national Irish guidelines.

      O'Kelly, R A; Byrne, E; Mulligan, C; Mulready, K J; O'Gorman, P; O'Shea, P; Boran, G; Coombe Women and Infants University Hospital, Dublin 8, Ireland, rokelly@coombe.ie. (2013-04-11)
      BACKGROUND: The Laboratory modernisation process in Ireland will include point of care testing (POCT) as one of its central tenets. However, a previous baseline survey showed that POCT was under-resourced particularly with respect to information technology (IT) and staffing. AIMS: An audit was undertaken to see if POCT services had improved since the publication of National Guidelines and if such services were ready for the major changes in laboratory medicine as envisaged by the Health Service Executive. METHODS: The 15 recommendations of the 2007 Guidelines were used as a template for a questionnaire, which was distributed by the Irish External Quality Assessment Scheme. RESULTS: Thirty-nine of a possible 45 acute hospitals replied. Only a quarter of respondent hospitals had POCT committees, however, allocation of staff to POCT had doubled since the first baseline survey. Poor IT infrastructure, the use of unapproved devices, and low levels of adverse incident reporting were still major issues. CONCLUSIONS: Point of care testing remains under-resourced, despite the roll out of such devices throughout the health service including primary care. The present high standards of laboratory medicine may not be maintained if the quality and cost-effectiveness of POCT is not controlled. Adherence to national Guidelines and adequate resourcing is essential to ensure patient safety.
    • Isolation of Staphylococcus aureus from screening swabs: comparison of blood agar and SAID, pre and post-enrichment.

      Meenan, A M; Maclellan, A; O'Sullivan, N; Hanniffy, R; Microbiology Department, Coombe Women and Infants University Hospital, Dublin,, Ireland. ameenan@coombe.ie (2012-02-01)
    • A less invasive approach to screening for early onset neonatal GBS.

      Glackin, S; Miletin, I; Deasy, A M (Irish Medical Journal, 2015-03)
      Recent recommendations for the management of an asymptomatic term infant with one septic risk factor for Group B Streptococcal (GBS) invasive disease have advised a clinical approach. Following a previous audit in our unit which showed that high numbers of asymptomatic infants were receiving antibiotics, a new protocol was introduced which emphasised the importance of clinical examination. This study assessed the safety and efficacy of this new protocol through chart review of 1855 eligible infants. We found a statistically significant decrease (P < 0.0001) from 444 (19%) to 121 (6.5%) in the total number of term infants who underwent septic evaluations and received antibiotics. 241 asymptomatic infants with one septic risk factor were managed conservatively. No eligible infants had GBS invasive disease during the three month study period. The new protocol is a safe and effective tool for evaluating infants at risk of GBS invasive disease.
    • Longitudinal study of aortic isthmus Doppler in appropriately grown and small-for-gestational-age fetuses with normal and abnormal umbilical artery Doppler.

      Kennelly, M M; Farah, N; Hogan, J; Reilly, A; Turner, M J; Stuart, B; Ultrasound and Fetal Medicine Centre, Coombe Women and Infants University Hospital, Dublin, Ireland. mkennelly@doctors.org.uk (2012-04)
      To establish reference ranges using longitudinal data for aortic isthmus (AoI) Doppler indices in appropriate-for-gestational-age (AGA) fetuses and to document the longitudinal trends in a cohort of small-for-gestational-age (SGA) fetuses with normal umbilical artery Doppler and in fetuses with intrauterine growth restriction (IUGR) and abnormal umbilical artery Doppler.