Seizure burden and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy.

Aim: To examine the relationship between electrographic seizures and long-term outcome in neonates with hypoxic-ischemic encephalopathy (HIE). Method: Full-term neonates with HIE born in Cork University Maternity Hospital from 2003 to 2006 (pre-hypothermia era) and 2009 to 2012 (hypothermia era) were included in this observational study. All had early continuous electroencephalography monitoring. All electrographic seizures were annotated. The total seizure burden and hourly seizure burden were calculated. Outcome (normal/abnormal) was assessed at 24 to 48 months in surviving neonates using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales; a diagnosis of cerebral palsy or epilepsy was also considered an abnormal outcome. Results: Continuous electroencephalography was recorded for a median of 57.1 hours (interquartile range 33.5-80.5h) in 47 neonates (31 males, 16 females); 29 out of 47 (62%) had electrographic seizures and 25 out of 47 (53%) had an abnormal outcome. The presence of seizures per se was not associated with abnormal outcome (p=0.126); however, the odds of an abnormal outcome increased over ninefold (odds ratio [OR] 9.56; 95% confidence interval [95% CI] 2.43-37.67) if a neonate had a total seizure burden of more than 40 minutes (p=0.001), and eightfold (OR: 8.00; 95% CI: 2.06-31.07) if a neonate had a maximum hourly seizure burden of more than 13 minutes per hour (p=0.003). Controlling for electrographic HIE grade or treatment with hypothermia did not change the direction of the relationship between seizure burden and outcome. Interpretation: In HIE, a high electrographic seizure burden is significantly associated with abnormal outcome, independent of HIE severity or treatment with hypothermia

Coagulation profiles are associated with early clinical outcomes in neonatal encephalopathy

Introduction: Neonatal encephalopathy (NE) is associated with coagulation abnormalities. We aimed to investigate the serial alterations in coagulation profiles in term infants with NE and correlate with their clinical outcomes. This was a prospective cohort study in a tertiary referral, university-affiliated maternity hospital. Neonates exposed to perinatal asphyxia were recruited (n = 82) and 39 received therapeutic hypothermia. Infants had serial coagulation tests including platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen in the first week of life. The main outcome measures included MRI brain and EEG seizures. Our results show that mortality was predicted on day 1 by decreased Fibrinogen (AUC = 0.95, p = 0.009) and by PT on day 2 with a cutoff of 22 s. An abnormal MRI was predicted by Fibrinogen on day 3 with a cut-off value of 2 g/L. For prediction of grade II/III NE, PT on day 2 of life was strongest with a cut-off value of 14 s. Only elevated APTT levels on day 1 of life were predictive of seizures (AUC = 0.65, p = 0.04). Conclusion: Coagulation parameters are strong predictors of outcomes such as abnormal NE grade, seizures, and mortality

Predicting success: patterns of cortical activation and deactivation prior to response inhibition

The present study investigated the relationships between attention and other preparatory processes prior to a response inhibition task and the processes involved in the inhibition itself. To achieve this, a mixed fMRI design was employed to identify the functional areas activated during both inhibition decision events and the block of trials following a visual cue introduced 2 to 7 sec prior (cue period). Preparing for successful performance produced increases in activation for both the cue period and the inhibition itself in the frontoparietal cortical network. Furthermore, preparation produced activation decreases in midline areas (insula and medial prefrontal) argued to be responsible for monitoring internal emotional states, and these cue period deactivations alone predicted subsequent success or failure. The results suggest that when cues are provided to signify the imminent requirement for behavioral control, successful performance results from a coordinated pattern of preparatory activation in task-relevant areas and deactivation of task-irrelevant ones

Oxytocin bolus versus oxytocin bolus and infusion for control of blood loss at elective caesarean section: double blind, placebo controlled, randomised trial

Objectives To determine the effects of adding an oxytocin infusion to bolus oxytocin on blood loss at elective caesarean section

MHC class II-restricted antigen presentation by plasmacytoid dendritic cells drives proatherogenic T cell immunity

Background—Plasmacytoid dendritic cells (pDCs) bridge innate and adaptive immune responses and are important regulators of immuno-inflammatory diseases. However, their role in atherosclerosis remains elusive. Methods and Results—Here, we used genetic approaches to investigate the role of pDCs in atherosclerosis. Selective pDC deficiency in vivo was achieved using CD11c-Cre × Tcf4–/flox bone marrow transplanted into Ldlr–/– mice. Compared with control Ldlr–/– chimeric mice, CD11c-Cre × Tcf4–/flox mice had reduced atherosclerosis levels. To begin to understand the mechanisms by which pDCs regulate atherosclerosis, we studied chimeric Ldlr–/– mice with selective MHCII deficiency on pDCs. Significantly, these mice also developed reduced atherosclerosis compared with controls without reductions in pDC numbers or changes in conventional DCs. MHCII-deficient pDCs showed defective stimulation of apolipoprotein B100–specific CD4+ T cells in response to native low-density lipoprotein, whereas production of interferon-α was not affected. Finally, the atheroprotective effect of selective MHCII deficiency in pDCs was associated with significant reductions of proatherogenic T cell–derived interferon-γ and lesional T cell infiltration, and was abrogated in CD4+ T cell–depleted animals. Conclusions—This study supports a proatherogenic role for pDCs in murine atherosclerosis and identifies a critical role for MHCII-restricted antigen presentation by pDCs in driving proatherogenic T cell immunity

Study Protocol. ECSSIT – Elective Caesarean Section Syntocinon® Infusion Trial. A multi-centre randomised controlled trial of oxytocin (Syntocinon®) 5 IU bolus and placebo infusion versus oxytocin 5 IU bolus and 40 IU infusion for the control of blood loss at elective caesarean section

<p>Abstract</p> <p>Background</p> <p>Caesarean section is one of the most commonly performed major operations in women throughout the world. Rates are escalating, with studies from the United States of America, the United Kingdom, China and the Republic of Ireland reporting rates between 20% and 25%. Operative morbidity includes haemorrhage, anaemia, blood transfusion and in severe cases, maternal death.</p> <p>The value of routine oxytocics in the third stage of vaginal birth has been well established and it has been assumed that these benefits apply to caesarean delivery as well. A slow bolus dose of oxytocin is recommended following delivery of the baby at caesarean section. Some clinicians use an additional infusion of oxytocin for a further period following the procedure. Intravenous oxytocin has a very short half-life (4–10 minutes) therefore the potential advantage of an oxytocin infusion is that it maintains uterine contractility throughout the surgical procedure and immediate postpartum period, when most primary haemorrhages occur. The few trials to date addressing the optimal approach to preventing haemorrhage at caesarean section have been under-powered to evaluate clinically important outcomes. There has been no trial to date comparing the use of an intravenous slow bolus of oxytocin versus an oxytocin bolus and infusion.</p> <p>Methods and design</p> <p>A multi-centre randomised controlled trial is proposed. The study will take place in five large maternity units in Ireland with collaboration between academics and clinicians in the disciplines of obstetrics and anaesthetics. It will involve 2000 women undergoing elective caesarean section after 36 weeks gestation. The main outcome measure will be major haemorrhage (blood loss >1000 ml). A study involving 2000 women will have 80% power to detect a 36% relative change in the risk of major haemorrhage with two-sided 5% alpha.</p> <p>Discussion</p> <p>It is both important and timely that we evaluate the optimal approach to the management of the third stage at elective caesarean section. Safe operative delivery is now a priority and a reality for many pregnant women. Obstetricians, obstetric anaesthetists, midwives and pregnant women need high quality evidence on which to base management approaches. The overall aim is to reduce maternal haemorrhagic morbidity and its attendant risks at elective caesarean section.</p> <p>Trial registration</p> <p>number: ISRCTN17813715</p

The impact of a ward-based pharmacy technician service

Background: Pharmacy technicians have been employed in hospital settings for many years, but only recently has the potential for service expansion been explored. There is a paucity of research on the impact of a ward-based pharmacy technician service (WBPTS) in this country. Purpose: To determine the impact of a WBPTS on medicine management systems, patient safety and healthcare costs. Methods: Sixteen wards were studied over 8 weeks; four ‘intervention’ wards (already assigned a WBPTS prior to the study) and 12 ‘control’ wards (whereby technicians provide a stock ‘top-up’ service). The ‘intervention’ wards comprised mainly of medical patients; a WBPT had been assigned to each of these wards as they were considered high activity wards. The control wards comprised both medical and surgical patients. The medication management systems were inspected by the research team for the presence of excess non-stock medicines and expired medication. Nurses were observed by the research team to calculate time taken to complete drug rounds. Patient drug charts were analysed to calculate the duration to pharmacist review of high-risk medications. Nursing staff were surveyed on their opinions of the service. Results: The total value of excess non-stock on intervention wards was €97.51 (mean cost per ward: €24.38) compared with €13,767.76 on the control wards (mean cost per ward: €1,147.31). Eight expired medications were found on control wards; none were present on intervention wards. The mean time to complete drug rounds on a per-patient basis was 28% lower on intervention wards. The median time taken for pharmacist review of high-risk medications was shorter on intervention wards (0.67 days vs 4.2 days). 100% of respondents agreed that the WBPTS should continue. Conclusion: More widespread investment in the WBPTS has the potential to reduce healthcare expenditure due to excess medicines, increase nursing time spent on direct care of patients, and reduce the potential for patient harm from high-risk medicines. The current study did not consider the costs associated with providing this service (e.g. personnel costs, additional time spent by the technician/ time saved by nurses etc.) and so further studies should consider the full economic costing of the service

The impact of a ward‐based pharmacy technician service in an Irish hospital

Introduction: Pharmacy technicians have been employed in hospital settings for many years, but only recently have their role been reviewed for potential expansion. Hospitals across Australia, the United Kingdom, and many other countries have implemented a ward‐based pharmacy technician service (1, 2), but this is yet to become common practice in Ireland. At present, there is only one published study on the development of the clinical role of pharmacy technicians in Ireland (3). Aim: The aim of this study was to determine if the expanded role of the ward‐based pharmacy technician role could have a positive impact on medicine management systems within a hospital ward. Methods: This study was carried out over 8 weeks in an Irish hospital. Sixteen wards were studied; four “intervention wards” which have the ward‐based technician service in situ, and 12 “control ward” which currently do not. Medicine management systems were assessed within these wards with respect to (1) the presence of excess non‐ward stock on drug trolleys, (2) the presence of expired medication on drug trolleys, and (3) the time taken by nurses to complete drug rounds. Results: The total cost value of the excess non‐stock items found on the intervention wards was €97.51 (the average cost per ward was €24.38). The total cost value of the excess non‐stock items found on the control wards was €13,767.76 (the average cost per ward was €1,147.31). Eight expired medications were found on the control wards; none were present on intervention wards. The ward‐based technician service reduced the average nursing time to complete drug rounds on a per‐patient basis by 28%. Conclusion: This study has demonstrated that the expanded role of the ward‐based pharmacy technician has had a positive impact in several ways; a reduction in the cost of non‐stock items present on the ward along with a reduction in expired stock present. Time taken to complete drug rounds was less on the intervention wards compared to control wards, thus, freeing up time for nurses to engage in other patient activities. Further studies should consider the full economic costing of the ward‐based pharmacy technician service

The Passive Journalist: How sources dominate the local news

This study explores which sources are “making” local news and whether these sources are simply indicating the type of news that appears, or are shaping newspaper coverage. It provides an empirical record of the extent to which sources are able to dominate news coverage from which future trends in local journalism can be measured. The type and number of sources used in 2979 sampled news stories in four West Yorkshire papers, representing the three main proprietors of local newspapers in the United Kingdom, were recorded for one month and revealed the relatively narrow range of routine sources; 76 per cent of articles cited only a single source. The analysis indicates that journalists are relying less on their readers for news, and that stories of little consequence are being elevated to significant positions, or are filling news pages at the expense of more important stories. Additionally, the reliance on a single source means that alternative views and perspectives relevant to the readership are being overlooked. Journalists are becoming more passive, mere processors of one-sided information or bland copy dictated by sources. These trends indicate poor journalistic standards and may be exacerbating declining local newspaper sales

"Pathogen Eradication" and "Emerging Pathogens": Difficult Definitions in Cystic Fibrosis.

Infection is a common complication of cystic fibrosis (CF) airway disease. Current treatment approaches include early intervention with the intent to eradicate pathogens in the hope of delaying the development of chronic infection and the chronic use of aerosolized antibiotics to suppress infection. The use of molecules that help restore CFTR (cystic fibrosis transmembrane conductance regulator) function, modulate pulmonary inflammation, or improve pulmonary clearance may also influence the microbial communities in the airways. As the pipeline of these new entities continues to expand, it is important to define when key pathogens are eradicated from the lungs of CF patients and, equally important, when new pathogens might emerge as a result of these novel therapies