Blanchardstown, Ireland
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Kollias A.,National and Kapodistrian University of Athens | Stergiou G.S.,National and Kapodistrian University of Athens | Dolan E.,Connolly Hospital | O'Brien E.,University College Dublin
Atherosclerosis | Year: 2012

Objective: The dynamic relationship between 24 h diastolic and systolic ambulatory blood pressure (BP) expressed by the ambulatory arterial stiffness index (AASI) has been introduced as a novel measure of arterial function, which independently predicts cardiovascular mortality. This article reviews the published evidence on the features and the clinical relevance of AASI. Methods: A systematic review and meta-analysis of the evidence on AASI from 51 cross-sectional and longitudinal studies in adults was conducted. Results: Studies of the reproducibility of AASI have shown a mean difference between assessments at 0.014 (95% CI -0.001, 0.028; 3 studies, n = 451) and repeatability coefficients ranging from 0.24 to 0.40. AASI appears to be independently associated with age, systolic BP and pulse pressure, and inversely with the nocturnal systolic and diastolic BP decline. A moderate pooled association of AASI with 24 h pulse pressure (pooled correlation coefficient r 0.47, 95% CI 0.40, 0.54; 20 studies, n = 29,186) and pulse wave velocity (pooled r 0.30, 95% CI 0.19, 0.42; 9 studies, n = 4123) was demonstrated, as well as with other measures of arterial function and target-organ damage. The adjusted pooled hazard ratio for stroke corresponding to a study-specific one standard deviation increase in AASI was 1.26 (95% CI 1.08, 1.45; 3 studies, n = 14,320). Conclusions: The available evidence suggests that AASI, obtained by ambulatory BP monitoring, predicts future cardiovascular events, particularly stroke, and is associated with indices of arterial function. The precise pathophysiological mechanisms remain obscure. Research is required to determine the usefulness of AASI as a therapeutic target in clinical practice. © 2012 Elsevier Ireland Ltd.

Garber A.J.,Baylor College of Medicine | King A.B.,Diabetes Care Center | Del Prato S.,University of Pisa | Sreenan S.,Connolly Hospital | And 6 more authors.
The Lancet | Year: 2012

Background Basal insulin therapy does not stop loss of ß-cell function, which is the hallmark of type 2 diabetes mellitus, and thus diabetes control inevitably deteriorates. Insulin degludec is a new, ultra-longacting basal insulin. We aimed to assess effi cacy and safety of insulin degludec compared with insulin glargine in patients with type 2 diabetes mellitus. Methods In this 52 week, phase 3, open-label, treat-to-target, non-inferiority trial, undertaken at 123 sites in 12 countries, we enrolled adults (aged =18 years) with type 2 diabetes mellitus and a glycated haemoglobin (HbA1c) of 7.0-10.0% after 3 months or more of any insulin regimen (with or without oral antidiabetic drugs). We randomly allocated eligible participants in a 3:1 ratio to receive once-daily subcutaneous insulin degludec or glargine, stratifi ed by previous insulin regimen, via a central interactive response system. Basal insulin was titrated to a target plasma glucose concentration of 3.9-<5.0 mmol/L self-measured before breakfast. The primary outcome was non-inferiority of degludec to glargine measured by change in HbA1c from baseline to week 52 (non-inferiority limit of 0.4%) by ANOVA in the full analysis set. We assessed rates of hypoglycaemia in all treated patients. This study is registered with, number NCT00972283. Findings 744 (99%) of 755 participants randomly allocated degludec and 248 (99%) of 251 allocated glargine were included in the full analysis set (mean age 58.9 years [SD 9.3], diabetes duration 13.5 years [7.3], HbA1c 8.3% [0.8], and fasting plasma glucose 9.2 mmol/L [3.1]); 618 (82%) and 211 (84%) participants completed the trial. After 1 year, HbA1c decreased by 1.1% in the degludec group and 1.2% in the glargine group (estimated treatment diff erence [degludec-glargine] 0.08%, 95% CI-0.05 to 0.21), confi rming non-inferiority. Rates of overall confi rmed hypoglycaemia (plasma glucose <3.1 mmol/L or severe episodes requiring assistance) were lower with degludec than glargine (11.1 vs 13.6 episodes per patient-year of exposure; estimated rate ratio 0.82, 95% CI 0.69 to 0.99; p=0.0359), as were rates of nocturnal confi rmed hypoglycaemia (1.4 vs 1.8 episodes per patient-year of exposure; 0.75, 0.58 to 0.99; p=0.0399). Rates of severe hypoglycaemia seemed similar (0.06 vs 0.05 episodes per patient-year of exposure for degludec and glargine) but were too low for assessment of diff erences. Rates of other adverse events did not diff er between groups. Interpretation A policy of suboptimum diabetes control to reduce the risk of hypoglycaemia and its consequences in advanced type 2 diabetes mellitus might be unwarranted with newer basal insulins such as degludec, which are associated with lower risks of hypoglycaemia than insulin glargine.

Hogan S.,Royal College of Surgeons in Ireland | Stevens N.T.,Royal College of Surgeons in Ireland | Humphreys H.,Royal College of Surgeons in Ireland | Humphreys H.,Beaumont Hospital | And 3 more authors.
Current Pharmaceutical Design | Year: 2015

Staphylococci, in particular Staphylococcus aureus and Staphylococcus epidermidis, are a leading cause of healthcareassociated infections. Patients who have a medical device inserted are at particular risk of an infection with these organisms as staphylococci possess a wide range of immune evasion mechanisms, one of which being their ability to form biofilm. Once embedded in a biofilm, bacteria are inherently more resistant to treatment with antibiotics. Despite advances in our understanding of the pathogenesis of staphylococcal biofilm formation, medical devices colonised with biofilms frequently require removal. New and novel approaches to prevent and treat biofilm infections are urgently required. In recent years, progress has been made on approaches that include antiadhesive strategies to prevent surface adhesion or production of bacterial adhesins, dissolution of already established biofilm, targeting of biofilm matrix for degradation and interference with biofilm regulation. Several obstacles need to be overcome in the further development of these and other novel anti-biofilm agents. Most notably, although in vitro investigation has progressed over recent years, the need for biofilm models to closely mimic the in vivo situation is of paramount importance followed by controlled clinical trials. In this review we highlight the issues associated with staphylococcal colonisation of medical devices and potential new treatment options for the prevention and control of these significant infections. © 2015 Bentham Science Publishers.

Kerley C.P.,Connolly Hospital | Kerley C.P.,University College Dublin | Elnazir B.,The National Childrens Hospital | Faul J.,Connolly Hospital | Cormican L.,Connolly Hospital
Pulmonary Pharmacology and Therapeutics | Year: 2015

Vitamin D deficiency (VDD) is highly prevalent worldwide. The classical role for vitamin D is to regulate calcium absorption form the gastrointestinal tract and influence bone health. Recently vitamin D receptors and vitamin D metabolic enzymes have been discovered in numerous sites systemically supporting diverse extra-skeletal roles of vitamin D, for example in asthmatic disease. Further, VDD and asthma share several common risk factors including high latitude, winter season, industrialization, poor diet, obesity, and dark skin pigmentation. Vitamin D has been demonstrated to possess potent immunomodulatory effects, including effects on T cells and B cells as well as increasing production of antimicrobial peptides (e.g. cathelicidin). This immunomodulation may lead to asthma specific clinical benefits in terms of decreased bacterial/viral infections, altered airway smooth muscle-remodeling and -function as well as modulation of response to standard anti-asthma therapy (e.g. glucocorticoids and immunotherapy).Thus, vitamin D and its deficiency have a number of biological effects that are potentially important in altering the course of disease pathogenesis and severity in asthma. The purpose of this first of a two-part review is to review potential mechanisms whereby altering vitamin D status may influence asthmatic disease. © 2015 Elsevier Ltd.

Rothwell P.M.,University of Oxford | Howard S.C.,University of Oxford | Dolan E.,Connolly Hospital | O'Brien E.,University College Dublin | And 4 more authors.
The Lancet Neurology | Year: 2010

Background: Analyses of some randomised trials show that calcium-channel blockers reduce the risk of stroke more than expected on the basis of mean blood pressure alone and that β blockers are less effective than expected. We aimed to investigate whether the effects of these drugs on variability in blood pressure might explain these disparities in effect on stroke risk. Methods: The Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm (ASCOT-BPLA) compared amlodipine-based regimens with atenolol-based regimens in 19 257 patients with hypertension and other vascular risk factors and the Medical Research Council (MRC) trial compared atenolol-based and diuretic-based regimens versus placebo in 4396 hypertensive patients aged 65-74 years. We expressed visit-to-visit variability of blood pressure during follow-up in the two trials as standard deviation (SD) and as transformations uncorrelated with mean blood pressure. For ASCOT-BPLA, we also studied within-visit variability and variability on 24 h ambulatory blood-pressure monitoring (ABPM). Results: In ASCOT-BPLA, group systolic blood pressure (SBP) SD was lower in the amlodipine group than in the atenolol group at all follow-up visits (p<0·0001), mainly because of lower within-individual visit-to-visit variability. Within-visit and ABPM variability in SBP were also lower in the amlodipine group than in the atenolol group (all p<0·0001). Analysis of changes from baseline showed that variability decreased over time in the amlodipine group and increased in the atenolol group. The lower risk of stroke in the amlodipine group (hazard ratio 0·78, 95% CI 0·67-0·90) was partly attenuated by adjusting for mean SBP during follow-up (0·84, 0·72-0·98), but was abolished by also adjusting for within-individual SD of clinic SBP (0·99, 0·85-1·16). Findings were similar for coronary events. In the ABPM substudy, reduced variability in daytime SBP in the amlodipine group (p<0·0001) partly accounted for the reduced risk of vascular events, but reduced visit-to-visit variability in clinic SBP had a greater effect. In the MRC trial, group SD SBP and all measures of within-individual visit-to-visit variability in SBP were increased in the atenolol group compared with both the placebo group and the diuretic group during initial follow-up (all p<0·0001). Subsequent temporal trends in variability in blood pressure during follow-up in the atenolol group correlated with trends in stroke risk. Interpretation: The opposite effects of calcium-channel blockers and β blockers on variability of blood pressure account for the disparity in observed effects on risk of stroke and expected effects based on mean blood pressure. To prevent stroke most effectively, blood-pressure-lowering drugs should reduce mean blood pressure without increasing variability; ideally they should reduce both. Funding: None. © 2010 Elsevier Ltd. All rights reserved.

Rothwell P.M.,University of Oxford | Howard S.C.,University of Oxford | Dolan E.,Connolly Hospital | O'Brien E.,University College Dublin | And 4 more authors.
The Lancet | Year: 2010

Background: The mechanisms by which hypertension causes vascular events are unclear. Guidelines for diagnosis and treatment focus only on underlying mean blood pressure. We aimed to reliably establish the prognostic significance of visit-to-visit variability in blood pressure, maximum blood pressure reached, untreated episodic hypertension, and residual variability in treated patients. Methods: We determined the risk of stroke in relation to visit-to-visit variability in blood pressure (expressed as standard deviation [SD] and parameters independent of mean blood pressure) and maximum blood pressure in patients with previous transient ischaemic attack (TIA; UK-TIA trial and three validation cohorts) and in patients with treated hypertension (Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm [ASCOT-BPLA]). In ASCOT-BPLA, 24-h ambulatory blood-pressure monitoring (ABPM) was also studied. Findings: In each TIA cohort, visit-to-visit variability in systolic blood pressure (SBP) was a strong predictor of subsequent stroke (eg, top-decile hazard ratio [HR] for SD SBP over seven visits in UK-TIA trial: 6·22, 95% CI 4·16-9·29, p<0·0001), independent of mean SBP, but dependent on precision of measurement (top-decile HR over ten visits: 12·08, 7·40-19·72, p<0·0001). Maximum SBP reached was also a strong predictor of stroke (HR for top-decile over seven visits: 15·01, 6·56-34·38, p<0·0001, after adjustment for mean SBP). In ASCOT-BPLA, residual visit-to-visit variability in SBP on treatment was also a strong predictor of stroke and coronary events (eg, top-decile HR for stroke: 3·25, 2·32-4·54, p<0·0001), independent of mean SBP in clinic or on ABPM. Variability on ABPM was a weaker predictor, but all measures of variability were most predictive in younger patients and at lower (

Kerley C.P.,Connolly Hospital | Kerley C.P.,University College Dublin | Elnazir B.,The National Childrens Hospital | Faul J.,Connolly Hospital | Cormican L.,Connolly Hospital
Pulmonary Pharmacology and Therapeutics | Year: 2015

Vitamin D deficiency (VDD) is highly prevalent worldwide, with adverse effects on bone health but also potentially other unfavorable consequences. VDD and asthma-incidence/severity share many common risk factors, including winter season, industrialization, poor diet, obesity, dark skin pigmentation, and high latitude. Multiple anatomical areas relevant to asthma contain both the enzyme responsible for producing activated vitamin D and the vitamin D receptor suggesting that activated vitamin D (1,25-dihydroxyvitamin D) may have important local effects at these sites. Emerging evidence suggests that VDD is associated with increased airway hyperresponsiveness, decreased pulmonary function, worse asthma control, and possibly decreased response to standard anti-asthma therapy. However the effect is inconsistent with preliminary evidence from different studies suggesting vitamin D is both beneficial and detrimental to asthma genesis and severity. Current evidence suggests that supplementation with moderate doses of vitamin D may be appropriate for maintenance of bone health in asthmatics, particularly steroid users. However emerging data from an increasing number of randomized, controlled, intervention studies of vitamin D supplementation in pediatric and adult asthma are becoming available and should help determine the importance, if any of vitamin D for asthma pathogenesis. The purpose of this second of a two-part review is to review the current human literature on vitamin D and asthma, discussing the possible consequences of VDD for asthma and the potential for vitamin D repletion as adjunct therapy. © 2015 Elsevier Ltd.

Dolan E.,Connolly Hospital | O'Brien E.,University College Dublin
Current Cardiology Reports | Year: 2015

Variability is a phenomenon common to most biological processes that we can measure and is a particular feature of blood pressure (BP). Variability causes concern for many physicians regarding its clinical meaning and potential impact on cardiovascular risk. In this review, we assess the role of different time periods of blood pressure variability (BPV) in cardiovascular risk stratification. We review the indices of BPV derived from ambulatory blood pressure measurement (ABPM), home blood pressure measurement (HBPM), or at the clinic setting with the intention of providing a clear message for clinical practice. BPV, either derived from ABPM or HBPM, does not consistently augment cardiovascular risk prediction over and beyond that of average BP, particularly in low-risk individuals. That said, it would seem that certain medications such as calcium channel blockers may have a beneficial effect on visit-to-visit BPV and perhaps reduce the associated cardiovascular risk. This highlights the benefits in using combination therapy which might couple a number of therapeutic benefits such as the reductions of mean blood pressure and BPV. Overall, we should remain aware that the average BP level remains the main modifiable risk factor derived from BP measurements and continue to improve the control of hypertension and adverse health outcomes. © 2015, Springer Science+Business Media New York.

Anyansi T.E.,Connolly Hospital | Agyapong V.I.O.,St James's Hospital
International Journal of Psychiatry in Clinical Practice | Year: 2013

Background. Predictive factors are used to alert the clinician to the necessity of carrying out a suicide risk assessment in those patients whose demographic and clinical characteristics suggest the possibility of suicide. Aim. To identify demographic and clinical variables that could predict suicidal ideation in psychiatric outpatients. Methods. 150 consecutive return patients attending a psychiatric outpatient clinic were approached and requested to complete a clinician-administered semi-structured questionnaire designed to assess the aims of the study. The questionnaire comprised 18 questions most of which had either a checklist of possible answers or a yes/no answer. Data was analysed with descriptive statistics, univariate analysis and logistic regression using SPSS version 17. Results. Of the 150 patients approached with written information, 133 consented to take part in the study giving a response rate of 88.7%. The mean age was 40.6 years (s.d = 12.7). On univariate analysis, there was a statistically significant relationship (P < 0.05) between three of the predictor variables (age, marital status and history of self-harm) and the likelihood of experiencing suicidal ideation in the preceding 12 months. However, with all other factors controlled for, only two of the independent variables (history of self-harm and no history of psychiatric inpatient treatment) significantly predicted suicidal ideation in the previous 12 months with odds ratios of 5.409 and 2.836 respectively. Conclusion. Amongst variables studied, having a history of self-harm or no previous history of psychiatric inpatient treatment was the best predictor of suicidal ideation in the preceding year in a population of patients attending a psychiatric outpatient review clinic. © 2013 Informa Healthcare.

Bannan N.,Connolly Hospital
Counselling and Psychotherapy Research | Year: 2010

Aims: The treatment of suicidal behaviour remains limited in efficacy. This pilot study assessed the effectiveness of a timelimited, group-based problem-solving therapy intervention compared with a treatment as usual control group, in females who self-poison. Method: A total of 18 clients were equally randomised to treatment or control groups. All clients were assessed using standardised questionnaires for depression, hopelessness, suicidal ideation and social problem-solving skills, at pre-treatment, post-treatment and two months follow-up. Results: The treatment group experienced significant reductions in levels of depression, hopelessness, suicidal ideation and improvements in self-assessed social problem-solving skills. Improvements in mental health and aspects of self-assessed problem-solving skills for the treatment group continued to be evident at two months follow-up. The control group did not change significantly over time on mental health measures or social problem solving abilities. Conclusion: Although limited by small sample size, the results suggest that group-based problem-solving therapy is effective in the management of deliberate self-poisoning. This paper is a unique contribution in that it examines the implementation of problem solving therapy with a homogenous population and in a group format. Methodological concerns and directions for future research are discussed. © 2010 British Association for Counselling and Psychotherapy.

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