• Trends in congenital anomalies in Europe from 1980 to 2012.

      Morris, Joan K; Springett, Anna L; Greenlees, Ruth; Loane, Maria; Addor, Marie-Claude; Arriola, Larraitz; Barisic, Ingeborg; Bergman, Jorieke E H; Csaky-Szunyogh, Melinda; Dias, Carlos; et al. (Plos One, 2018-01-01)
      Surveillance of congenital anomalies is important to identify potential teratogens. This study analysed the prevalence of 61 congenital anomaly subgroups (excluding chromosomal) in 25 population-based EUROCAT registries (1980-2012). Live births, fetal deaths and terminations of pregnancy for fetal anomaly were analysed with multilevel random-effects Poisson regression models. Seventeen anomaly subgroups had statistically significant trends from 2003-2012; 12 increasing and 5 decreasing. The annual increasing prevalence of severe congenital heart defects, single ventricle, atrioventricular septal defects and tetralogy of Fallot of 1.4% (95% CI: 0.7% to 2.0%), 4.6% (1.0% to 8.2%), 3.4% (1.3% to 5.5%) and 4.1% (2.4% to 5.7%) respectively may reflect increases in maternal obesity and diabetes (known risk factors). The increased prevalence of cystic adenomatous malformation of the lung [6.5% (3.5% to 9.4%)] and decreased prevalence of limb reduction defects [-2.8% (-4.2% to -1.5%)] are unexplained. For renal dysplasia and maternal infections, increasing trends may be explained by increased screening, and deceases in patent ductus arteriosus at term and increases in craniosynostosis, by improved follow up period after birth and improved diagnosis. For oesophageal atresia, duodenal atresia/stenosis and ano-rectal atresia/stenosis recent changes in prevalence appeared incidental when compared with larger long term fluctuations. For microcephaly and congenital hydronephrosis trends could not be interpreted due to discrepancies in diagnostic criteria. The trends for club foot and syndactyly disappeared once registries with disparate results were excluded. No decrease in neural tube defects was detected, despite efforts at prevention through folic acid supplementation.
    • Trends in employment for individuals with autism spectrum disorder: a review of the research literature

      Chen, June L.; Leader, Geraldine; Sung, Connie; Leahy, Michael (2014-12-24)
    • Trends in the incidence of lower extremity amputations in people with and without diabetes over a five-year period in the Republic of Ireland.

      Buckley, Claire M; O'Farrell, Anne; Canavan, Ronan J; Lynch, Anthony D; De La Harpe, Davida V; Bradley, Colin P; Perry, Ivan J (2012)
      To describe trends in the incidence of non-traumatic amputations among people with and without diabetes and estimate the relative risk of an individual with diabetes undergoing a lower extremity amputation compared to an individual without diabetes in the Republic of Ireland.
    • Trends in the obstetric features and management of twin pregnancies.

      Smith, K E; Ravikumar, N; Hession, M; Morrison, J J; Department of Obstetrics and Gynaecology, NUIG, Galway University Hospital, Newcastle Road, Galway. (2010-03)
      There are no reports outlining the trends in obstetric features and clinical management of twin pregnancies in an Irish obstetric population. The aim of this study was to investigate these factors for all twin pregnancies delivered during the 19 year period between 1989 and 2007, at Galway University Hospital (GUH). There were 52,199 infants delivered at GUH, of which 1594 infants (3.05% of births) were twins, related to 797 twin pregnancies. The overall incidence of twin pregnancies was 1.52%, increasing from 0.8%-1.0% in the early years of the study to 1.7-1.8% in the latter years of the study (P<0.001). There was a significant increase in incidence of twins born to mothers aged 30-39 years, alongside a significant reduction to mothers aged 20-29 years (P<0.01). The caesarean section rate overall was 41.5% (331/797), of which 54% (n=179) were elective, and 46% (n=152) were emergency, representing an emergency caesarean section rate of 19.1% of all twin pregnancies, and of 24.6% after exclusion of elective caesarean sections. The caesarean section rate for twins increased from 30% in 1989 to greater than 50% in the latter years of the study (P<0.01), related largely to a significant increase in elective caesarean sections (P<0.01). The combined vaginal-caesarean delivery rate was remarkably low at 0.75% of all twin pregnancies, and 1% after exclusion of elective caesarean sections. The preterm delivery rates were 4.1% (<32 weeks), and 16.3% (<36 weeks), with an overall perinatal mortality rate of 37 per 1000. These findings highlight the altered demographic and clinical aspects of twin pregnancies in an Irish obstetric population.
    • Trends in the prevalence, risk and pregnancy outcome of multiple births with congenital anomaly: a registry-based study in 14 European countries 1984-2007

      Boyle, B; McConkey, R; Garne, E; Loane, M; Addor, MC; Bakker, MK; Boyd, PA; Gatt, M; Greenlees, R; Haeusler, M; et al. (2014-07-18)
    • Trends of selected malformations in relation to folic acid recommendations and fortification: an international assessment.

      Botto, Lorenzo D; Lisi, Alessandra; Bower, Carol; Canfield, Mark A; Dattani, Nirupa; De Vigan, Catherine; De Walle, Hermien; Erickson, David J; Halliday, Jane; Irgens, Lorentz M; et al. (2006-10)
      Two crucial issues relative to the benefits and impact of folic acid in the prevention of birth defects are whether supplementation recommendations alone, without fortification, are effective in reducing the population-wide rates of neural tube defects (NTDs), and whether such policies can reduce the occurrence of other birth defects. Using data from 15 registries, we assessed rates and trends of 14 major defects, including NTDs, in areas with official recommendations or fortification to assess the effectiveness of recommendations and fortification on a wide range of major birth defects.
    • Triggers of self-conscious emotions in the sexually transmitted infection testing process

      Balfe, Myles; Brugha, Ruairi; O' Donovan, Diarmuid; O' Connell, Emer; Vaughan, Deirdre (2010-08-17)
      Abstract Background Self-conscious emotions (shame, guilt and embarrassment) are part of many individuals' experiences of seeking STI testing. These emotions can have negative impacts on individuals' interpretations of the STI testing process, their willingness to seek treatment and their willingness to inform sexual partners in light of positive STI diagnoses. Because of these impacts, researchers have called for more work to be completed on the connections between shame, guilt, embarrassment and STI testing. We examine the specific events in the STI testing process that trigger self-conscious emotions in young adults who seek STI testing; and to understand what it is about these events that triggers these emotions. Semi-structured interviews with 30 adults (21 women, 9 men) in the Republic of Ireland. Findings Seven specific triggers of self-conscious emotions were identified. These were: having unprotected sex, associated with the initial reason for seeking STI testing; talking to partners and peers about the intention to seek STI testing; the experience of accessing STI testing facilities and sitting in clinic waiting rooms; negative interactions with healthcare professionals; receiving a positive diagnosis of an STI; having to notify sexual partners in light of a positive STI diagnosis; and accessing healthcare settings for treatment for an STI. Self-conscious emotions were triggered in each case by a perceived threat to respondents' social identities. Conclusion There are multiple triggers of self-conscious emotions in the STI testing process, ranging from the initial decision to seek testing, right through to the experience of accessing treatment. The role of self-conscious emotions needs to be considered in each component of service design from health promotion approaches, through facility layout to the training of all professionals involved in the STI testing process.
    • Tumor specific HMG-CoA reductase expression in primary pre-menopausal breast cancer predicts response to tamoxifen

      Brennan, Donal J; Laursen, Henriette; O'Connor, Darran P; Borgquist, Signe; Uhlen, Mathias; Gallagher, Willam M; Ponten, Fredrik; Millikan, Robert C; Ryden, Lisa; Jirstrom, Karin (2011-01-31)
      Abstract Introduction We previously reported an association between tumor-specific 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) expression and a good prognosis in breast cancer. Here, the predictive value of HMG-CoAR expression in relation to tamoxifen response was examined. Methods HMG-CoAR protein and RNA expression was analyzed in a cell line model of tamoxifen resistance using western blotting and PCR. HMG-CoAR mRNA expression was examined in 155 tamoxifen-treated breast tumors obtained from a previously published gene expression study (Cohort I). HMG-CoAR protein expression was examined in 422 stage II premenopausal breast cancer patients, who had previously participated in a randomized control trial comparing 2 years of tamoxifen with no systemic adjuvant treatment (Cohort II). Kaplan-Meier analysis and Cox proportional hazards modeling were used to estimate the risk of recurrence-free survival (RFS) and the effect of HMG-CoAR expression on tamoxifen response. Results HMG-CoAR protein and RNA expression were decreased in tamoxifen-resistant MCF7-LCC9 cells compared with their tamoxifen-sensitive parental cell line. HMG-CoAR mRNA expression was decreased in tumors that recurred following tamoxifen treatment (P < 0.001) and was an independent predictor of RFS in Cohort I (hazard ratio = 0.63, P = 0.009). In Cohort II, adjuvant tamoxifen increased RFS in HMG-CoAR-positive tumors (P = 0.008). Multivariate Cox regression analysis demonstrated that HMG-CoAR was an independent predictor of improved RFS in Cohort II (hazard ratio = 0.67, P = 0.010), and subset analysis revealed that this was maintained in estrogen receptor (ER)-positive patients (hazard ratio = 0.65, P = 0.029). Multivariate interaction analysis demonstrated a difference in tamoxifen efficacy relative to HMG-CoAR expression (P = 0.05). Analysis of tamoxifen response revealed that patients with ER-positive/HMG-CoAR tumors had a significant response to tamoxifen (P = 0.010) as well as patients with ER-positive or HMG-CoAR-positive tumors (P = 0.035). Stratification according to ER and HMG-CoAR status demonstrated that ER-positive/HMG-CoAR-positive tumors had an improved RFS compared with ER-positive/HMG-CoAR-negative tumors in the treatment arm (P = 0.033); this effect was lost in the control arm (P = 0.138), however, suggesting that HMG-CoAR predicts tamoxifen response. Conclusions HMG-CoAR expression is a predictor of response to tamoxifen in both ER-positive and ER-negative disease. Premenopausal patients with tumors that express ER or HMG-CoAR respond to adjuvant tamoxifen.
    • Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer

      Brennan, Donal J; Brandstedt, Jenny; Rexhepaj, Elton; Foley, Michael; Ponten, Fredrik; Uhlen, Mathias; Gallagher, William M; O'Connor, Darran P; O'Herlihy, Colm; Jirstrom, Karin (2010-04-01)
      Abstract Background Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. Methods HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). Results Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. Conclusion HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.
    • Tumour-specific HMG-CoAR is an independent predictor of recurrence free survival in epithelial ovarian cancer.

      Brennan, Donal J; Brändstedt, Jenny; Rexhepaj, Elton; Foley, Michael; Pontén, Fredrik; Uhlén, Mathias; Gallagher, William M; O'Connor, Darran P; O'Herlihy, Colm; Jirstrom, Karin; et al. (2010)
      BACKGROUND: Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer. METHODS: HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS). RESULTS: Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade. CONCLUSION: HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.
    • Turning Vision into Reality - Irish Medical Organisation Benchmark study

      Irish Medical Organisation (IMO) (Irish Medical Organisation (IMO), 2018-03-15)
    • Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening

      Loane, Maria; Morris, Joan K; Addor, Marie-Claude; Arriola, Larraitz; Budd, Judith; Doray, Berenice; Garne, Ester; Gatt, Miriam; Haeusler, Martin; Khoshnood, Babak; et al. (2014-07-18)
    • Two birds with one stone: experiences of combining clinical and research training in addiction medicine

      Klimas, J.; McNeil, R.; Ahamad, K.; Mead, A.; Rieb, L.; Cullen, W.; Wood, E.; Small, W. (2017-01-23)
    • Two patients walk into a clinic...a genomics perspective on the future of schizophrenia

      Corvin, Aiden P (2011-11-11)
      Abstract Progress is being made in schizophrenia genomics, suggesting that this complex brain disorder involves rare, moderate to high-risk mutations and the cumulative impact of small genetic effects, coupled with environmental factors. The genetic heterogeneity underlying schizophrenia and the overlap with other neurodevelopmental disorders suggest that it will not continue to be viewed as a single disease. This has radical implications for clinical practice, as diagnosis and treatment will be guided by molecular etiology rather than clinical diagnostic criteria.
    • The two peptide lantibiotic lacticin 3147 acts synergistically with polymyxin to inhibit Gram negative bacteria

      Draper, Lorraine A; Cotter, Paul D; Hill, Colin; Ross, R P (2013-09-26)
      Abstract Background The emergence of bacterial drug resistance encourages the re-evaluation of the potential of existing antimicrobials. Lantibiotics are post-translationally modified, ribosomally synthesised antimicrobial peptides with a broad spectrum antimicrobial activity. Here, we focussed on expanding the potential of lacticin 3147, one of the most studied lantibiotics and one which possesses potent activity against a wide range of Gram positive species including many nosocomial pathogens. More specifically, our aim was to investigate if lacticin 3147 activity could be enhanced when combined with a range of different clinical antibiotics. Results Initial screening revealed that polymyxin B and polymyxin E (colistin) exhibited synergistic activity with lacticin 3147. Checkerboard assays were performed against a number of strains, including both Gram positive and Gram negative species. The resultant fractional inhibitory concentration (FIC) index values established that, while partial synergy was detected against Gram positive targets, synergy was obvious against Gram negative species, including Cronobacter and E. coli. Conclusions Combining lacticin 3147 with low levels of a polymyxin could provide a means of broadening target specificity of the lantibiotic, while also reducing polymyxin use due to the lower concentrations required as a result of synergy.
    • Types of bruxism

      McAuliffe, Dr Padraig (Irish Dental Association, 2012-06)
    • Typical investigational medicinal products follow relatively uniform regulations in 10 European Clinical Research Infrastructures Network (ECRIN) countries

      Gluud, Christian; Kubiac, Christine; Whitfield, Kate; Byrne, Jane; Huemer, Karl-Heinz; Thirstrup, Steffen; Libersa, Christian; Barraud, Beatrice; Grahlert, Xina; Dreier, Gabriele; et al. (2012-03-27)
      Abstract Background In order to facilitate multinational clinical research, regulatory requirements need to become international and harmonised. The EU introduced the Directive 2001/20/EC in 2004, regulating investigational medicinal products in Europe. Methods We conducted a survey in order to identify the national regulatory requirements for major categories of clinical research in ten European Clinical Research Infrastructures Network (ECRIN) countries-Austria, Denmark, France, Germany, Hungary, Ireland, Italy, Spain, Sweden, and United Kingdom-covering approximately 70% of the EU population. Here we describe the results for regulatory requirements for typical investigational medicinal products, in the ten countries. Results Our results show that the ten countries have fairly harmonised definitions of typical investigational medicinal products. Clinical trials assessing typical investigational medicinal products require authorisation from a national competent authority in each of the countries surveyed. The opinion of the competent authorities is communicated to the trial sponsor within the same timelines, i.e., no more than 60 days, in all ten countries. The authority to which the application has to be sent to in the different countries is not fully harmonised. Conclusion The Directive 2001/20/EC defined the term 'investigational medicinal product' and all regulatory requirements described therein are applicable to investigational medicinal products. Our survey showed, however, that those requirements had been adopted in ten European countries, not for investigational medicinal products overall, but rather a narrower category which we term 'typical' investigational medicinal products. The result is partial EU harmonisation of requirements and a relatively navigable landscape for the sponsor regarding typical investigational medicinal products.
    • Ubiquitination of the bacterial inositol phosphatase, SopB, regulates its biological activity at the plasma membrane.

      Knodler, Leigh A; Winfree, Seth; Drecktrah, Dan; Ireland, Robin; Steele-Mortimer, Olivia; Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840, USA. lknodler@niaid.nih.gov (2009-11)
      The Salmonella type III effector, SopB, is an inositol polyphosphate phosphatase that modulates host cell phospholipids at the plasma membrane and the nascent Salmonella-containing vacuole (SCV). Translocated SopB persists for many hours after infection and is ubiquitinated but the significance of this covalent modification has not been investigated. Here we identify by mass spectrometry six lysine residues of SopB that are mono-ubiquitinated. Substitution of these six lysine residues with arginine, SopB-K(6)R, almost completely eliminated SopB ubiquitination. We found that ubiquitination does not affect SopB stability or membrane association, or SopB-dependent events in SCV biogenesis. However, two spatially and temporally distinct events are dependent on ubiquitination, downregulation of SopB activity at the plasma membrane and prolonged retention of SopB on the SCV. Activation of the mammalian pro-survival kinase Akt/PKB, a downstream target of SopB, was intensified and prolonged after infection with the SopB-K(6)R mutant. At later times, fewer SCV were decorated with SopB-K(6)R compared with SopB. Instead SopB-K(6)R was present as discrete vesicles spread diffusely throughout the cell. Altogether, our data show that ubiquitination of SopB is not related to its intracellular stability but rather regulates its enzymatic activity at the plasma membrane and intracellular localization.
    • Ultra high risk of psychosis on committal to a young offender prison: an unrecognised opportunity for early intervention

      Flynn, Darran; Smith, Damian; Quirke, Luke; Monks, Stephen; Kennedy, Harry G (2012-08-03)
      Abstract Background The ultra high risk state for psychosis has not been studied in young offender populations. Prison populations have higher rates of psychiatric morbidity and substance use disorders. Due to the age profile of young offenders one would expect to find a high prevalence of individuals with pre-psychotic or ultra-high risk mental states for psychosis (UHR). Accordingly young offender institutions offer an opportunity for early interventions which could result in improved long term mental health, social and legal outcomes. In the course of establishing a mental health in-reach service into Ireland’s only young offender prison, we sought to estimate unmet mental health needs. Methods Every third new committal to a young offenders prison was interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to identify the Ultra High Risk (UHR) state and a structured interview for assessing drug and alcohol misuse according to DSM-IV-TR criteria, the Developmental Understanding of Drug Misuse and Dependence - Short Form (DUNDRUM-S). Results Over a twelve month period 171 young male offenders aged 16 to 20 were assessed. Of these 39 (23%, 95% confidence interval 18% to 30%) met UHR criteria. UHR states peaked at 18 years, were associated with lower SOFAS scores for social and occupational function and were also associated with multiple substance misuse. The relationship with lower SOFAS scores persisted even when co-varying for multiple substance misuse. Conclusions Although psychotic symptoms are common in community samples of children and adolescents, the prevalence of the UHR state in young offenders was higher than reported for community samples. The association with impaired function also suggests that this may be part of a developing disorder. Much more attention should be paid to the relationship of UHR states to substance misuse and to the health needs of young offenders.
    • Ultrasound measurement of the size of the anterior tibial muscle group: the effect of exercise and leg dominance

      McCreesh, Karen; Egan, Sinead (2011-09-13)
      Abstract Background Knowledge of normal muscle characteristics is crucial in planning rehabilitation programmes for injured athletes. There is a high incidence of ankle and anterior tibial symptoms in football players, however little is known about the effect of limb dominance on the anterior tibial muscle group (ATMG). The purpose of this study was to assess the effect of limb dominance and sports-specific activity on ATMG thickness in Gaelic footballers and non-football playing controls using ultrasound measurements, and to compare results from transverse and longitudinal scans. Methods Bilateral ultrasound scans were taken to assess the ATMG size in 10 Gaelic footballers and 10 sedentary controls (age range 18-25 yrs), using a previously published protocol. Both transverse and longitudinal images were taken. Muscle thickness measurements were carried out blind to group and side of dominance, using the Image-J programme. Results Muscle thickness on the dominant leg was significantly greater than the non-dominant leg in the footballers with a mean difference of 7.3%, while there was no significant dominance effect in the controls (p < 0.05). There was no significant difference between the measurements from transverse or longitudinal scans. Conclusions A significant dominance effect exists in ATMG size in this group of Gaelic footballers, likely attributable to the kicking action involved in the sport. This should be taken into account when rehabilitating footballers with anterior tibial pathology. Ultrasound is a reliable tool to measure ATMG thickness, and measurement may be taken in transverse or longitudinal section.