• Doctors working within public health services

      Murphy, JFA (Irish Medical Journal, 2014-07)
    • Doctors' perspectives on the barriers to appropriate prescribing in older hospitalized patients: A qualitative study.

      Cullinan, S; Fleming, A; O'Mahony, D; Ryan, C; O'Sullivan, D; Gallagher, P; Byrne, S; Cavanagh Pharmacy Building, College Road, Cork, Ireland. (British journal of clinical pharmacology, 2014-11-18)
      Older patients commonly suffer from multimorbidites and take multiple medications. As a result, these patients are more vulnerable to potentially inappropriate prescribing (PIP). PIP in older patients may result in adverse drug events and hospitalisations. However, little has been done to identify why PIP occurs. The objectives of this study were; (1) to identify hospital doctors' perceptions as to why PIP occurs, (2) to identify the barriers to addressing the issues identified, and (3) to determine which intervention types would be best suited to improving prescribing.
    • Does a patient's physical activity predict recovery from an episode of acute low back pain? A prospective cohort study

      Hendrick, Paul; Milosavljevic, Stephan; Hale, Leigh; Hurley, Deirdre A; McDonough, Suzanne M; Herbison, Peter; Baxter, G David (2013-04-05)
      Abstract Background Advice to remain active and normalisation of activity are commonly prescribed in the management of low back pain (LBP). However, no research has assessed whether objective measurements of physical activity predict outcome and recovery in acute low back pain. Method The aims of this study were to assess the predictive relationship between activity and disability at 3 months in a sub-acute LBP population. This prospective cohort study recruited 101 consenting patients with sub-acute LBP (< 6 weeks) who completed the Roland Morris Disability Questionnaire (RMDQ), the Visual Analogue Scale, and resumption of full ‘normal’ activity question (Y/N), at baseline and 3 months. Physical activity was measured for 7 days at both baseline and at 3 months with an RT3 accelerometer and a recall questionnaire. Results Observed and self-reported measures of physical activity at baseline and change in activity from baseline to 3 months were not independent predictors of RMDQ (p > 0.05) or RMDQ change (p > 0.05) over 3 months. A self-report of a return to full ‘normal’ activities was significantly associated with greater RMDQ change score at 3 months (p < 0.001). Paired t-tests found no significant change in activity levels measured with the RT3 (p = 0.57) or the recall questionnaire (p = 0.38) from baseline to 3 months. Conclusions These results question the predictive role of physical activity in LBP recovery, and the assumption that activity levels change as LBP symptoms resolve. The importance of a patient’s perception of activity limitation in recovery from acute LBP was also highlighted. Trial registration Clinical Trial Registration Number, ACTRN12609000282280
    • Does HIPE data capture the complexity of stroke patients in an acute hospital setting?

      Clarke, B; Kennelly, S; Shanley, D; Hogan-Lowe, D; McCormack, P M E (2010-01)
      The Hospital Inpatient Enquiry (HIPE) system is currently used as a principle source of national data on discharges from acute hospitals. The Casemix Programme is used to calculate funding for patient care (HIPE activity and Specialty Costs Returns). Th coding is usually undertaken by clerical personnel. We were concerned that the medical complexity of our stroke patients was not captured by the process. The aims of this study were to compare activity coded by HIPE coding staff and medical staff in consecutive stroke patients discharged from the hospital. One hundred consecutive discharged patients with stroke as primary diagnosis were coded by clerical staff [usual practice] and by medical staff. We compared the coding and any differences. We calculated the financial comparison of subsequent differences in Diagnostic Related Groups (DRGs) and Relative Values (RVs). Clinician coded DRGs resulted in a higher assigned RV in 45 cases. The total RV value for HIPE using clerical coding was 595,268.94 euros and using medical coding was 725,252.16 euros. We conclude that medical input is useful in detailing the complications arising in stroke patients. We suggest that physicians should assist in the HIPE coding process in order to capture clinical complexity, so that funding can be appropriately assigned to manage these complex patients.
    • Does physical activity change predict functional recovery in low back pain? Protocol for a prospective cohort study

      Hendrick, Paul; Milosavljevic, Stephan; Bell, Melanie L; Hale, Leigh; Hurley, Deirdre A; McDonough, Suzanne M; Melloh, Markus; Baxter, David G (2009-11-06)
      Abstract Background Activity advice and prescription are commonly used in the management of low back pain (LBP). Although there is evidence for advising patients with LBP to remain active, facilitating both recovery and return to work, to date no research has assessed whether objective measurements of free living physical activity (PA) can predict outcome, recovery and course of LBP. Methods An observational longitudinal study will investigate PA levels in a cohort of community-dwelling working age adults with acute and sub-acute LBP. Each participant's PA level, functional status, mood, fear avoidance behaviours, and levels of pain, psychological distress and occupational activity will be measured on three occasions during for 1 week periods at baseline, 3 months, and 1 year. Physical activity levels will be measured by self report, RT3 triaxial accelerometer, and activity recall questionnaires. The primary outcome measure of functional recovery will be the Roland Morris Disability Questionnaire (RMDQ). Free living PA levels and changes in functional status will be quantified in order to look at predictive relationships between levels and changes in free living PA and functional recovery in a LBP population. Discussion This research will investigate levels and changes in activity levels of an acute LBP cohort and the predictive relationship to LBP recovery. The results will assess whether occupational, psychological and behavioural factors affect the relationship between free living PA and LBP recovery. Results from this research will help to determine the strength of evidence supporting international guidelines that recommend restoration of normal activity in managing LBP. Trial registration [Clinical Trial Registration Number, ACTRN12609000282280]
    • Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome and healthy control participants: study protocol for an exploratory randomized double- blind placebo-controlled trial

      O’Connell, Karen; Kelly, Siobhan; Kinsella, Katie; Jordan, Sinead; Kenny, Orla; Murphy, David; Heffernan, Eric; O’Laoide, Risteard; O’Shea, Donal; McKenna, Carmel; et al. (2013-08-27)
      Abstract Background There is increasing evidence linking vitamin D deficiency to both susceptibility to, and severity of, multiple sclerosis (MS). Patients with the clinically isolated syndrome represent the initial presentation of a demyelinating disorder, and those with asymptomatic lesions on magnetic resonance imaging (MRI) are at risk of progression to clinically definite MS. The aims of this study are to examine the immunologic effects of vitamin D in both healthy individuals and in patients with clinically isolated syndrome, and in the latter group the effects on disease progression assessed by MRI and clinical measures. Methods/Design This is a single-center double-blind randomized placebo-controlled clinical trial. The primary endpoint is the immunologic effects of two doses of vitamin D compared with placebo over 24 weeks in both healthy control participants and patients presenting with the clinically isolated syndrome. Healthy control participants (n = 39) and patients with clinically isolated syndrome (n = 45) will be randomized to one of three arms, namely 1) vitamin D 5,000 IU daily, 2) vitamin D 10,000 IU daily, or 3) placebo, and followed up for 24 weeks. In both patients and healthy control participants, the primary outcome will be immunologic measures of the frequency of CD4 T-cell subsets and cytokine responses in peripheral blood mononuclear cells, assessed at baseline, and after 16 and 24 weeks of treatment. Secondary endpoints, in the patients with clinically isolated syndrome, will be relapse activity, and the number of new T2 lesions and gadolinium-enhancing lesions assessed by MRI in the two vitamin D-treated groups compared with the placebo-treated group over the 24 weeks of the study. Trial registration EU Clinical Trials Register: EudraCT: 2012-000635-68. ClinicalTrials.gov identifier: NCT01728922
    • Dropout and related factors in therapy

      Egan, Jonathan; Health Service Executive (HSE) Midland (The Irish Psychologist, 2005-09)
    • Drug suicide: a sex-equal cause of death in 16 European countries

      Varnik, Airi; Sisask, Merike; Varnik, Peeter; Wu, Jing; Kolves, Kairi; Arensman, Ella; Maxwell, Margareth; Reisch, Thomas; Gusmao, Ricardo; van Audenhove, Chantal; et al. (2011-01-29)
      Abstract Background There is a lack of international research on suicide by drug overdose as a preventable suicide method. Sex- and age-specific rates of suicide by drug self-poisoning (ICD-10, X60-64) and the distribution of drug types used in 16 European countries were studied, and compared with other self-poisoning methods (X65-69) and intentional self-injury (X70-84). Methods Data for 2000-04/05 were collected from national statistical offices. Age-adjusted suicide rates, and age and sex distributions, were calculated. Results No pronounced sex differences in drug self-poisoning rates were found, either in the aggregate data (males 1.6 and females 1.5 per 100,000) or within individual countries. Among the 16 countries, the range (from some 0.3 in Portugal to 5.0 in Finland) was wide. 'Other and unspecified drugs' (X64) were recorded most frequently, with a range of 0.2-1.9, and accounted for more than 70% of deaths by drug overdose in France, Luxembourg, Portugal and Spain. Psychotropic drugs (X61) ranked second. The X63 category ('other drugs acting on the autonomic nervous system') was least frequently used. Finland showed low X64 and high X61 figures, Scotland had high levels of X62 ('narcotics and hallucinogens, not elsewhere classified') for both sexes, while England exceeded other countries in category X60. Risk was highest among the middle-aged everywhere except in Switzerland, where the elderly were most at risk. Conclusions Suicide by drug overdose is preventable. Intentional self-poisoning with drugs kills as many males as females. The considerable differences in patterns of self-poisoning found in the various European countries are relevant to national efforts to improve diagnostics of suicide and appropriate specific prevention. The fact that vast majority of drug-overdose suicides came under the category X64 refers to the need of more detailed ICD coding system for overdose suicides is needed to permit better design of suicide-prevention strategies at national level.
    • Dual channel rank-based intensity weighting for quantitative co-localization of microscopy images

      Singan, Vasanth R; Jones, Thouis R; Curran, Kathleen M; Simpson, Jeremy C (2011-10-21)
      Abstract Background Accurate quantitative co-localization is a key parameter in the context of understanding the spatial co-ordination of molecules and therefore their function in cells. Existing co-localization algorithms consider either the presence of co-occurring pixels or correlations of intensity in regions of interest. Depending on the image source, and the algorithm selected, the co-localization coefficients determined can be highly variable, and often inaccurate. Furthermore, this choice of whether co-occurrence or correlation is the best approach for quantifying co-localization remains controversial. Results We have developed a novel algorithm to quantify co-localization that improves on and addresses the major shortcomings of existing co-localization measures. This algorithm uses a non-parametric ranking of pixel intensities in each channel, and the difference in ranks of co-localizing pixel positions in the two channels is used to weight the coefficient. This weighting is applied to co-occurring pixels thereby efficiently combining both co-occurrence and correlation. Tests with synthetic data sets show that the algorithm is sensitive to both co-occurrence and correlation at varying levels of intensity. Analysis of biological data sets demonstrate that this new algorithm offers high sensitivity, and that it is capable of detecting subtle changes in co-localization, exemplified by studies on a well characterized cargo protein that moves through the secretory pathway of cells. Conclusions This algorithm provides a novel way to efficiently combine co-occurrence and correlation components in biological images, thereby generating an accurate measure of co-localization. This approach of rank weighting of intensities also eliminates the need for manual thresholding of the image, which is often a cause of error in co-localization quantification. We envisage that this tool will facilitate the quantitative analysis of a wide range of biological data sets, including high resolution confocal images, live cell time-lapse recordings, and high-throughput screening data sets.
    • Duplicability of self-interacting human genes.

      Pérez-Bercoff, Asa; Makino, Takashi; McLysaght, Aoife; Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin 2, Ireland. (2010)
      BACKGROUND: There is increasing interest in the evolution of protein-protein interactions because this should ultimately be informative of the patterns of evolution of new protein functions within the cell. One model proposes that the evolution of new protein-protein interactions and protein complexes proceeds through the duplication of self-interacting genes. This model is supported by data from yeast. We examined the relationship between gene duplication and self-interaction in the human genome. RESULTS: We investigated the patterns of self-interaction and duplication among 34808 interactions encoded by 8881 human genes, and show that self-interacting proteins are encoded by genes with higher duplicability than genes whose proteins lack this type of interaction. We show that this result is robust against the system used to define duplicate genes. Finally we compared the presence of self-interactions amongst proteins whose genes have duplicated either through whole-genome duplication (WGD) or small-scale duplication (SSD), and show that the former tend to have more interactions in general. After controlling for age differences between the two sets of duplicates this result can be explained by the time since the gene duplication. CONCLUSIONS: Genes encoding self-interacting proteins tend to have higher duplicability than proteins lacking self-interactions. Moreover these duplicate genes have more often arisen through whole-genome rather than small-scale duplication. Finally, self-interacting WGD genes tend to have more interaction partners in general in the PIN, which can be explained by their overall greater age. This work adds to our growing knowledge of the importance of contextual factors in gene duplicability.
    • Dysregulated miR-183 inhibits migration in breast cancer cells.

      Lowery, Aoife J; Miller, Nicola; Dwyer, Roisin M; Kerin, Michael J; Department of Surgery, National University of Ireland, Galway, Ireland. (2010)
      The involvement of miRNAs in the regulation of fundamental cellular functions has placed them at the fore of ongoing investigations into the processes underlying carcinogenesis. MiRNA expression patterns have been shown to be dysregulated in numerous human malignancies, including breast cancer, suggesting their probable involvement as novel classes of oncogenes or tumour suppressor genes. The identification of differentially expressed miRNAs and elucidation of their functional roles may provide insight into the complex and diverse molecular mechanisms of tumorigenesis. MiR-183 is located on chromosome 7q32 and is part of a miRNA family which are dysregulated in numerous cancers. The aims of this study were to further examine the expression and functional role of miR-183 in breast cancer.
    • Early additional food and fluids for healthy breastfed full-term infants: Cochrane Systematic Review

      BEST Services, Galway, Ireland; University of Liverpool, Department of Women's and Children's Health, Liverpool, UK (Cochrane Database of Systematic Reviews, 2014-11-24)
    • Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy

      Nadeem, Montasser; Murray, Deirdre M; Boylan, Geraldine B; Dempsey, Eugene M; Ryan, Cornelius A (2011-02-04)
      Abstract Background To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. Methods Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [< 46.8 mg/dL (2.6 mmol/L)] and hyperglycaemia [> 150 mg/dL (8.3 mmol/L)] were correlated to neurodevelopmental outcome at 24 months of age. Results Four fifths of the 468 blood samples were in the normoglycaemic range (392/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11/39) and a third of the hyperglycaemic samples (32.4%:12/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol/L and 5.02(2.35) mmol/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. Conclusion During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome.
    • Early life exposure to chronic intermittent Hypoxia Primes Increased Susceptibility to Hypoxia-Induced Weakness in Rat Sternohyoid Muscle during adulthood.

      McDonald, Fiona B; Dempsey, Eugene M; O'Halloran, Ken D (Frontiers in Physiology, 2016-03)
      Intermittent hypoxia is a feature of apnea of prematurity (AOP), chronic lung disease, and sleep apnea. Despite the clinical relevance, the long-term effects of hypoxic exposure in early life on respiratory control are not well defined. We recently reported that exposure to chronic intermittent hypoxia (CIH) during postnatal development (pCIH) causes upper airway muscle weakness in both sexes, which persists for several weeks. We sought to examine if there are persistent sex-dependent effects of pCIH on respiratory muscle function into adulthood and/or increased susceptibility to re-exposure to CIH in adulthood in animals previously exposed to CIH during postnatal development. We hypothesized that pCIH would cause long-lasting muscle impairment and increased susceptibility to subsequent hypoxia. Within 24 h of delivery, pups and their respective dams were exposed to CIH: 90 s of hypoxia reaching 5% O2 at nadir; once every 5 min, 8 h per day for 3 weeks. Sham groups were exposed to normoxia in parallel. Three groups were studied: sham; pCIH; and pCIH combined with adult CIH (p+aCIH), where a subset of the pCIH-exposed pups were re-exposed to the same CIH paradigm beginning at 13 weeks. Following gas exposures, sternohyoid and diaphragm muscle isometric contractile and endurance properties were examined ex vivo. There was no apparent lasting effect of pCIH on respiratory muscle function in adults. However, in both males and females, re-exposure to CIH in adulthood in pCIH-exposed animals caused sternohyoid (but not diaphragm) weakness. Exposure to this paradigm of CIH in adulthood alone had no effect on muscle function. Persistent susceptibility in pCIH-exposed airway dilator muscle to subsequent hypoxic insult may have implications for the control of airway patency in adult humans exposed to intermittent hypoxic stress during early life.
    • Early life opportunities for prevention of diabetes in low and middle income countries

      Hanson, Mark A; Gluckman, Peter D; Ma, Ronald CW; Matzen, Priya; Biesma, Regien G (2012-11-23)
      Abstract Background The global burden of diabetes and other non-communicable diseases is rising dramatically worldwide and is causing a double poor health burden in low- and middle-income countries. Early life influences play an important part in this scenario because maternal lifestyle and conditions such as gestational diabetes and obesity affect the risk of diabetes in the next generation. This indicates important periods during the lifecourse when interventions could have powerful affects in reducing incidence of non-communicable diseases. However, interventions to promote diet and lifestyle in prospective parents before conception have not received sufficient attention, especially in low- and middle-income countries undergoing socio-economic transition. Discussion Interventions to produce weight loss in adults or to reduce weight gain in pregnancy have had limited success and might be too late to produce the largest effects on the health of the child and his/her later risk of non-communicable diseases. A very important factor in the prevention of the developmental component of diabetes risk is the physiological state in which the parents enter pregnancy. We argue that the most promising strategy to improve prospective parents’ body composition and lifestyle is the promotion of health literacy in adolescents. Multiple but integrated forms of community-based interventions that focus on nutrition, physical activity, family planning, breastfeeding and infant feeding practices are needed. They need to address the wider social economic context in which adolescents live and to be linked with existing public health programmes in sexual and reproductive health and maternal and child health initiatives. Summary Interventions aimed at ensuring a healthy body composition, diet and lifestyle before pregnancy offer a most effective solution in many settings, especially in low- and middle-income countries undergoing socio-economic transition. Preparing a mother, her partner and her future child for “the 1000 days”, whether from planned or unplanned conception would break the cycle of risk and demonstrate benefit in the shortest possible time. Such interventions will be particularly important in adolescents and young women in disadvantaged groups and can improve the physiological status of the fetus as well as reduce the prevalence of pregnancy conditions such as gestational diabetes mellitus which both predispose to non-communicables diseases in both the mother and her child. Pre-conception interventions require equipping prospective parents with the necessary knowledge and skills to make healthy lifestyle choices for themselves and their children. Addressing the promotion of such health literacy in parents-to-be in low- and middle-income countries requires a wider social perspective. It requires a range of multisectoral agencies to work together and could be linked to the issues of women’s empowerment, to reproductive health, to communicable disease prevention and to the Millennium Development Goals 4 and 5.
    • Early life socioeconomic adversity is associated in adult life with chronic inflammation, carotid atherosclerosis, poorer lung function and decreased cognitive performance: a cross-sectional, population-based study

      Packard, Chris J; Bezylak, Vladimir; McLean, Jennifer S; Batty, G David; Ford, Ian; Burns, Harry; Cavanagh, Jonathan; Deans, Kevin A; Henderson, Marion; McGinty, Agnes; et al. (2011-01-17)
      Abstract Background Socioeconomic gradients in health persist despite public health campaigns and improvements in healthcare. The Psychosocial and Biological Determinants of Ill-health (pSoBid) study was designed to uncover novel biomarkers of chronic disease that may help explain pathways between socioeconomic adversity and poorer physical and mental health. Methods We examined links between indicators of early life adversity, possible intermediary phenotypes, and markers of ill health in adult subjects (n = 666) recruited from affluent and deprived areas. Classical and novel risk factors for chronic disease (lung function and atherosclerosis) and for cognitive performance were assessed, and associations sought with early life variables including conditions in the parental home, family size and leg length. Results Associations were observed between father's occupation, childhood home status (owner-occupier; overcrowding) and biomarkers of chronic inflammation and endothelial activation in adults (C reactive protein, interleukin 6, intercellular adhesion molecule; P < 0.0001) but not number of siblings and leg length. Lung function (forced expiratory volume in 1 second) and cognition (Choice Reaction Time, the Stroop test, Auditory Verbal Learning Test) were likewise related to early life conditions (P < 0.001). In multivariate models inclusion of inflammatory variables reduced the impact and independence of early life conditions on lung function and measures of cognitive ability. Including variables of adult socioeconomic status attenuated the early life associations with disease biomarkers. Conclusions Adverse levels of biomarkers of ill health in adults appear to be influenced by father's occupation and childhood home conditions. Chronic inflammation and endothelial activation may in part act as intermediary phenotypes in this complex relationship. Reducing the 'health divide' requires that these life course determinants are taken into account.
    • Early orthognathic surgery in response to bullying due to malocclusion

      O’Keefe, Con (Irish Dental Association, 2017-01)