Migratory history of the threespine stickleback Gasterosteus aculeatus in western Ireland.

Microchemical analysis of trace elements in otoliths and bio-mineralised earstones of teleost fishes is an emerging approach to analysing the environmental migratoryand life histories of fish species. The migration history of the three-spine stickleback (Gasterosteus aculeatus) collected in western Ireland was examined using calcium (Ca) and strontium (Sr) concentrations in otoliths. The otolith Sr:Ca values fluctuated with the habitat. The habitat use and migration history of G. aculeatus can be categorised into two types, as determined by the mean value and life history transect of the otolith Sr:Ca; that is, freshwater and estuarine residents, whereas there were no anadromous sticklebacks which is believed to be a typical migration pattern in the species. The otolith Sr:Ca profiles of the freshwater resident fishes exhibited constantly low Sr:Ca values, averaging 0.41-0.58 × 10-3 from the core towards the edge. However, the otolith Sr:Ca profiles of the estuarine resident fishes exhibited constantly high Sr:Ca values from the core towards the edge without a clear transition point from low to high Sr:Ca values, as found in the anadromous fish, averaging 1.82-4.26 × 10-3. The present study is the first published confirmation that 100 % of sticklebacks living in coastal habitats in Ireland > have an estuarine resident migratory pattern, constantly residing in marine environments or brackish water throughout their lifespan and not in freshwater environments in Ireland.

Experience of women on the Irish National Gestational Trophoblastic Disease Registry.

OBJECTIVE: Gestational Trophoblastic Disease (GTD) is a rare pregnancy related disorder and the most curable of all gynaecological malignancies. GTD comprises the premalignant conditions of complete or partial hydatidiform mole known as molar pregnancy and a spectrum of malignant disorders termed gestational trophoblastic neoplasia. Clinical management and treatment in specialist centres is essential to achieve high cure rates and clinical guidelines recommend registration with a GTD centre as a minimum standard of care. National GTD registries are valuable repositories of epidemiological data and facilitate clinical audit, centralised pathology review and human chorionic gonadotropin (hCG) monitoring. This study sought the opinion of women enrolled on the Irish National GTD registry to inform future service development and establish a knowledge base for molar pregnancy in Ireland. STUDY DESIGN: A cross-sectional survey using an anonymised questionnaire was distributed by post to all women on the GTD registry. The questionnaire was designed by a multidisciplinary team and consisted of twenty-five closed-ended questions and two open-ended questions to facilitate feedback. Data collected in the survey included information on the patient experience of registration, knowledge of molar pregnancy, diagnosis at their local hospital, hCG monitoring and overall satisfaction with the service. RESULTS: The survey had a successful participation rate of 42.6% (215/504). Forty-nine percent (n = 106) of respondents rated a rapid hCG result as their top priority. Forty percent (n = 84) of women had concerns about future pregnancies but acknowledged that these were largely addressed by the GTD specialist nurses. A quarter of respondents reported that other medical professionals with whom they interacted during follow-up treatment did not understand their condition. Many women commented on the emotional stress of attending their local maternity unit for phlebotomy while dealing with pregnancy loss. CONCLUSION: This study is unique in being the first survey of women on the Irish National GTD registry. It highlights the specific needs of women with molar pregnancy in terms of psychological support, bereavement counselling and peer support groups. It reveals a knowledge gap in molar pregnancy amongst healthcare professionals which should be considered in future planning of medical and nursing curricula.

The cost of callbacks: return visits for diagnostic imaging discrepancies in a pediatric emergency department.

PURPOSE: Diagnostic imaging has mirrored the steady growth of healthcare utilization in the USA. This has created greater opportunity for diagnostic errors, which can be costly in terms of morbidity and mortality as well as dollars and cents. The purposes of this study were to describe all return visits to a tertiary care urban pediatric emergency department (PED) resulting from diagnostic imaging discrepancies and to calculate the costs of these return visits. METHODS: From July 2014 to February 2015, all children who underwent a diagnostic imaging study during an ED visit were assembled. Analysis was performed on all children who were called back and returned to the ED following a discrepant read. Direct and indirect costs to the patient, family, hospital, and society for these return visits were calculated. RESULTS: During the study period, 8310 diagnostic imaging studies were performed, with 207 (2.5%) discrepant reads. Among the discrepant reads, 37 (0.4% of total, 17.9% of discrepant) patients had a return visit to the ED for further management. Including ED charges, time and travel costs to the family, and costs of radiation exposure, return visits for radiologic discrepancies over this 8-month period cost a total of $84,686.47, averaging $2288.82 per patient. CONCLUSIONS: Though the overall diagnostic imaging discrepancy rate among our study population was low, the clinically significant discrepancies requiring return ED visits were potentially high risk, and costly for the patient, family, and healthcare system.

Cancer Incidence and Mortality due to Excess Body Weight in Ireland: An Analysis of 10-year data.

Excess body weight (EBW) increases the risk of specific cancers. The prevalence of EBW has risen significantly in Ireland over recent decades. To highlight the impact on cancer, and to inform future policies, we calculated the proportion of cancers in Ireland that were attributable to EBW using the Population Attributable Fraction (PAF). This fraction was then applied to Irish incidence and mortality data for specific cancers from 2003-2012 to estimate the number of new cancers and cancer deaths attributable to EBW. We found that each year in Ireland, approximately 800 new cancers and 300 cancer deaths are attributable to EBW. The greatest attributable risk of cancer was seen for the upper digestive tract and endometrium, whilst breast and colorectal have the greatest numbers of attributable cancers. EBW is a major cause of cancer, responsible for 4.5% of all cancers in Ireland. Public awareness of this significant preventable risk must improve.

Cost-Effectiveness of Watchful Waiting in Acute Otitis Media.

BACKGROUND: American Academy of Pediatrics guidelines for acute otitis media (AOM) allow for children meeting certain criteria to undergo watchful waiting (WW). The cost-effectiveness of this policy has not been evaluated in the United States. METHODS: A retrospective review of a random selection of 250 patients ≤18 years old with AOM in the emergency department of a tertiary care children's hospital was used to characterize current practice of AOM management. These data were incorporated into a decision-analytic cost-utility model comparing the cost-effectiveness of implementing WW to current practice. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed in 2015 USD per disability-adjusted life year (DALY) averted from a societal perspective. Multiple sensitivity analyses were conducted. RESULTS: From this cohort, chart review confirmed 247 actually had AOM on physical examination. Of these, 231 (93.5%) were prescribed antibiotics, 7 (2.8%) underwent WW, and 9 (3.6%) were sent home without an antibiotic prescription. When American Academy of Pediatrics criteria for WW were applied to this population, 104 patients (42.1%) met conditions for immediate antibiotic prescription, and 143 patients (57.9%) qualified for WW. In our modeled scenario, for every 1000 patients with AOM, implementing WW yielded 514 fewer immediate antibiotic prescriptions and 205 fewer antibiotic prescriptions used, averting 14.3 DALYs, and saving $5573. The preferability of WW over current practice proved highly robust to sensitivity analysis. CONCLUSIONS: WW for AOM management is cost-effective. Implementing WW may improve outcomes and reduce health care expenditures.

Total hip arthroplasty in patients with haemophilia - What are the risks of bleeding in the immediate peri-operative period?

BACKGROUND: Undergoing a major surgical intervention such as total hip arthroplasty (THA) with an underlying clotting disorder like haemophilia poses its own unique challenges. Despite the advances in factor replacement and medical management, the potential for excessive and uncontrolled haemorrhage still exists. The aim of this study was to quantify blood loss, peri-operative transfusion requirements and risk of haematoma formation in a cohort of patients with haemophilia undergoing THA. METHODS: All patients with haemophilia types A or B who had undergone THA in the previous 10 years were identified from the Hospital In-Patient Enquiry system and theatre logs. A comprehensive review of operative records, laboratory parameters and peri-operative haematological management was conducted. RESULTS: Eleven male patients (12 THA) were identified. The mean age was 56 years (range 28-76). The mean intra-operative blood loss was 502 ml (100-1250 ml) compared to an established normal blood loss of 400 ml. The mean drop in haemoglobin was 3.25 g/dl in 48 h. Only one patient required a post-operative transfusion of two units of red cell concentrate. There were no complications of haematoma formation. CONCLUSION: The results in our institution compare favourably with the established blood loss reported in the literature and by assessment with International Guidelines. Average blood loss in patients with haemophilia was higher than the established normal, but there was no increased transfusion requirement.

Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer.

BACKGROUND: Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 receptor (AT2R). In contrast, AT2R antagonist EMA401 has shown analgesic efficacy in animal models and clinical trials for neuropathic pain. We therefore investigated the morphological and functional effects of mycolactone in cultured human and rat dorsal root ganglia (DRG) neurons and the role of AT2R using EMA401. Primary sensory neurons were prepared from avulsed cervical human DRG and rat DRG; 24 h after plating, neurons were incubated for 24 to 96 h with synthetic mycolactone A/B, followed by immunostaining with antibodies to PGP9.5, Gap43, ß tubulin, or Mitotracker dye staining. Acute functional effects were examined by measuring capsaicin responses with calcium imaging in DRG neuronal cultures treated with mycolactone. RESULTS: Morphological effects: Mycolactone-treated cultures showed dramatically reduced numbers of surviving neurons and non-neuronal cells, reduced Gap43 and ß tubulin expression, degenerating neurites and reduced cell body diameter, compared with controls. Dose-related reduction of neurite length was observed in mycolactone-treated cultures. Mitochondria were distributed throughout the length of neurites and soma of control neurons, but clustered in the neurites and soma of mycolactone-treated neurons. Functional effects: Mycolactone-treated human and rat DRG neurons showed dose-related inhibition of capsaicin responses, which were reversed by calcineurin inhibitor cyclosporine and phosphodiesterase inhibitor 3-isobutyl-1-Methylxanthine, indicating involvement of cAMP/ATP reduction. The morphological and functional effects of mycolactone were not altered by Angiotensin II or AT2R antagonist EMA401. CONCLUSION: Mycolactone induces toxic effects in DRG neurons, leading to impaired nociceptor function, neurite degeneration, and cell death, resembling the cutaneous hypoalgesia and nerve damage in individuals with M. Ulcerans infection.

War and Marriage: Assortative Mating and the World War II GI Bill.

World War II and its subsequent GI Bill have been widely credited with playing a transformative role in American society, but there have been few quantitative analyses of these historical events' broad social effects. We exploit between-cohort variation in the probability of military service to investigate how WWII and the GI Bill altered the structure of marriage, and find that it had important spillover effects beyond its direct effect on men's educational attainment. Our results suggest that the additional education received by returning veterans caused them to "sort" into wives with significantly higher levels of education. This suggests an important mechanism by which socioeconomic status may be passed on to the next generation.

Long-term follow-up of women with breast cancer: rationale for policy change.

BACKGROUND: The number of breast cancer survivors in our ageing population continues to rise. Policy makers internationally are seeking to identify alternatives to follow-up care in an acute setting. AIMS: The National Cancer Control Programme set out to develop a new policy for long-term follow-up of breast cancer survivors in Ireland. METHODS: Policy development was informed by analysis of current attendances at breast surgical clinics for routine follow-up, extraction of the necessary components of follow-up from international guidelines and focus group research with Irish patients. RESULTS: Intensive follow-up investigations, other than mammography, do not confer additional survival benefit or improved quality of life. Provision of routine follow-up care of breast cancer survivors by GPs has been shown to be equivalent to follow-up by specialist clinics, in terms of clinical outcomes, patient quality of life and patient satisfaction. In Ireland, routine follow-up accounted for 15.4% (95% CI: 13.8-17.0%) of clinic appointments. A third were at least 5 years post-operative. Women highlighted issues such as attachment to specialist services, importance of communication and need for clarity as to where responsibility of care lies. Reassurance, confidence in the primary care practitioner, and coordination of multiple appointments were also identified as important issues. CONCLUSION: A significant proportion of breast cancer survivors attending hospital surgical clinics for long-term follow-up could be safely discharged at 5 years, with the hospital maintaining responsibility for annual mammography. Successful implementation will depend on informed patients, clinicians' acceptance and communication between primary and secondary care.

Surgery of the femur in HIV positive patients: a retrospective review from 2005 to 2011.

BACKGROUND: There are an estimated 6,900 people with HIV living in Ireland. There is a significant prevalence of femoral osteonecrosis and risk factors for osteoporotic fractures. With this potential, increasing surgical workload, it is important to assess surgical demand and audit outcomes. METHODS: The hospital's electronic records were examined. Between January 2005 and August 2011, 17 femoral surgeries were identified in seven patients. Patient records were retrospectively reviewed. RESULTS: Elective operations undertaken were eight hip replacements and one nail dynamisation. Eight emergency operations were undertaken: two DHS, one plating, one nailing, one revision nailing, two incision and drainages and one biopsy. All procedures were carried out using appropriate safety guidelines. Indications for surgery included femoral head osteonecrosis (n = 7), osteomyelitis (n = 3), proximal femoral fracture (n = 2), femoral shaft non-union (n = 1), dynamisation of a nail (n = 1), osteoarthritis (n = 1), fractured femur (n = 1), and revision nailing (n = 1). For two procedures the patient was not on highly active anti-retroviral treatment. All elective patients had CD4 counts greater than 200 pre-operatively. Six patients had undetectable viral loads. Of the eight emergency procedures, four procedures had no preoperative immune status recorded. Complications recorded were three non-unions, one nail fracture, one lesser trochanter fracture and recurrence of osteomyelitis. No surgical site infections were recorded. CONCLUSIONS: Complications were not related to immune status. The rate of surgical site infection in both elective and emergency procedures was low. The elective surgery patients can safely receive orthopaedic treatment in their regional orthopaedic unit. Due to the high non-infectious complication rates recorded in the emergency group, transfer to a tertiary facility with infectious disease expertise is advised.

Clinical doses of atomoxetine significantly occupy both norepinephrine and serotonin transports: Implications on treatment of depression and ADHD.

BACKGROUND: Atomoxetine (ATX), a drug for treatment of depression and ADHD, has a high affinity for the norepinephrine transporter (NET); however, our previous study showed it had a blocking effect similar to fluoxetine on binding of [(11)C]DASB, a selective serotonin transporter (SERT) ligand. Whether the therapeutic effects of ATX are due to inhibition of either or both transporters is not known. Here we report our comparative PET imaging studies with [(11)C]MRB (a NET ligand) and [(11)C]AFM (a SERT ligand) to evaluate in vivo IC50 values of ATX in monkeys. METHODS: Rhesus monkeys were scanned up to four times with each tracer with up to four doses of ATX. ATX or saline (placebo) infusion began 2h before each PET scan, lasting until the end of the 2-h scan. The final infusion rates were 0.01-0.12mg/kg/h and 0.045-1.054mg/kg/h for the NET and SERT studies, respectively. ATX plasma levels and metabolite-corrected arterial input functions were measured. Distribution volumes (VT) and IC50 values were estimated. RESULTS: ATX displayed dose-dependent occupancy on both NET and SERT, with a higher occupancy on NET: IC50 of 31±10 and 99±21ng/mL plasma for NET and SERT, respectively. At a clinically relevant dose (1.0-1.8mg/kg, approx. 300-600ng/mL plasma), ATX would occupy >90% of NET and >85% of SERT. This extrapolation assumes comparable free fraction of ATX in humans and non-human primates. CONCLUSION: Our data suggests that ATX at clinically relevant doses greatly occupies both NET and SERT. Thus, therapeutic modes of ATX action for treatment of depression and ADHD may be more complex than selective blockade of NET.

A survey of upper and lower limb tourniquet use among Irish orthopaedic surgeons.

BACKGROUND: Tourniquet use in orthopaedic surgery is common practice. However, the technique varies among Irish orthopaedic surgeons and there are no standard guidelines. AIM: To analyse trends in tourniquet use among Irish orthopaedic surgeons. METHODS: Ninety-two Irish orthopaedic consultants were sent a 15-survey question about tourniquet use by post. RESULTS: Sixty respondents returned a completed survey, of which 49 (81% of respondents) used both upper arm and thigh tourniquets. A variation in tourniquet pressure settings and techniques used was reported. Thirty-nine surgeons (65% of respondents) use a tourniquet pressure range of 201-250 mmHg for the upper arm and 30 surgeons (50% of respondents) use a range of 251-300 mmHg for the thigh. Thirty-six surgeons (60 % of respondents) experienced a complication secondary to tourniquet use, the most common complications being nerve and skin injury. CONCLUSIONS: Based on published studies of limb occlusion pressures, this study suggests that some of the tourniquet cuff inflation pressures used may be higher than necessary. Guidelines for optimising cuff pressure and technique should be established to minimise the risk of complications. This study may help determine direction for future research on tourniquet use.

Angiotensin II type 2 receptor (AT2 R) localization and antagonist-mediated inhibition of capsaicin responses and neurite outgrowth in human and rat sensory neurons.

BACKGROUND: The angiotensin II (AngII) receptor subtype 2 (AT2 R) is expressed in sensory neurons and may play a role in nociception and neuronal regeneration. METHODS: We used immunostaining with characterized antibodies to study the localization of AT2 R in cultured human and rat dorsal root ganglion (DRG) neurons and a range of human tissues. The effects of AngII and AT2 R antagonist EMA401 on capsaicin responses in cultured human and rat (DRG) neurons were measured with calcium imaging, on neurite length and density with Gap43 immunostaining, and on cyclic adenosine monophosphate (cAMP) expression using immunofluorescence. RESULTS: AT2 R expression was localized in small-/medium-sized cultured neurons of human and rat DRG. Treatment with the AT2 R antagonist EMA401 resulted in dose-related functional inhibition of capsaicin responses (IC50 = 10 nmol/L), which was reversed by 8-bromo-cAMP, and reduced neurite length and density; AngII treatment significantly enhanced capsaicin responses, cAMP levels and neurite outgrowth. The AT1 R antagonist losartan had no effect on capsaicin responses. AT2 R was localized in sensory neurons of human DRG, and nerve fibres in peripheral nerves, skin, urinary bladder and bowel. A majority sub-population (60%) of small-/medium-diameter neuronal cells were immunopositive in both control post-mortem and avulsion-injured human DRG; some very small neurons appeared to be intensely immunoreactive, with TRPV1 co-localization. While AT2 R levels were reduced in human limb peripheral nerve segments proximal to injury, they were preserved in painful neuromas. CONCLUSIONS: AT2 R antagonists could be particularly useful in the treatment of chronic pain and hypersensitivity associated with abnormal nerve sprouting.

Cancer incidence and mortality due to alcohol: an analysis of 10-year data.

Alcohol consumption is causally related to cancer of the upper aero-digestive tract, liver, colon, rectum, female breast and pancreas. The dose response relationship varies for each site. We calculated Ireland's cancer incidence and mortality attributable to alcohol over a 10-year period. Between 2001 and 2010, 4,585 (4.7%) male and 4,593 (4.2%) female invasive cancer diagnoses were attributable to alcohol. The greatest risk was for the upper aero-digestive tract where 2,961 (52.9%) of these cancers in males and 866 (35.2%) in females were attributable to alcohol. Between 2001 and 2010, 2,823 (6.7%) of male cancer deaths and 1,700 (4.6%) of female cancer deaths were attributable to alcohol. Every year approximately 900 new cancers and 500 cancer deaths are attributable to alcohol. Alcohol is a major cause of cancer after smoking, obesity and physical inactivity. Public awareness of risk must improve. Over half of alcohol related cancers are preventable by adhering to Department of Health alcohol consumption guidelines.

Characterization of the bovine innate immune response in milk somatic cells following intramammary infection with Streptococcus dysgalactiae subspecies dysgalactiae.

The innate immune response of milk somatic cells in cows to Streptococcus dysgalactiae ssp. dysgalactiae was investigated by deliberate intramammary challenge. Cows were challenged with 2,500 colony-forming units of Strep. dysgalactiae DPC 5435, previously isolated from a clinical mastitis case. Eight of the 9 cows treated showed clinical signs of mastitis (swollen udders, increased somatic cell score, and clotted milk) within 1 wk of challenge. Messenger RNA levels of IL-1ß and toll-like receptor 4 (TLR4) in milk somatic cells increased approximately 40 fold within 48 h of infusion, whereas tumor necrosis factor α increased 16 fold within the same time frame. Interestingly, cows homozygous for the G allele of the C-X-C chemokine receptor type 1 (CXCR1)-777 polymorphism had higher IL-8 and CXCR1 transcript abundance at 24h postinfusion compared with cows homozygous for the C allele. The difference in expression of these genes at this critical time point may influence the severity of disease within different genotypes.

Ability of non-invasive intermittent blood pressure monitoring and a continuous non-invasive arterial pressure monitor (CNAP™) to provide new readings in each 1-min interval during elective caesarean section under spinal anaesthesia.

We compared the ability of automated non-invasive intermittent oscillometric blood pressure monitoring with a new device, CNAP(TM) (continuous non-invasive arterial pressure) to provide a new blood pressure reading in each 1-min interval between spinal anaesthesia and delivery during caesarean section. We also compared the accuracy of continuous non-invasive arterial pressure readings with non-invasive blood pressure measurements before spinal anaesthesia. Fifty-nine women participated. The non-invasive and continuous non-invasive monitors displayed new blood pressure readings in a mean of 82% (11%) and 83% (13%) (p = 0.97) of the one-minute intervals between spinal anaesthesia and delivery, respectively. Continuous non-invasive arterial pressure was more likely to fail on two or more consecutive minutes (p=0.001). From the pre-spinal readings, the mean bias, defined as non-invasive-continuous non-invasive arterial pressure, and limits of agreement (±2SD mean bias) for systolic, diastolic and mean blood pressure respectively were +1.3 (±26.0), -2.9 (±21.8) and +2.6 (±20.4) mmHg. The new monitor has disadvantages compared with conventional non-invasive intermittent blood pressure monitoring.

Psychological adjustment to Type 2 diabetes and relationship quality.

AIMS: To examine the associations between psychological adjustment to Type 2 diabetes and the reported quality and type of relationships with partners. METHODS: All participants (n=88) completed a number of questionnaires, including two measures of relationship quality: the Dyadic Adjustment Scale and the Personal Assessment of Intimacy in Relationships Scale, the Diabetes Quality of Life Scale and the ATT-19 (which assesses personal integration of diabetes). Additionally, HbA(1c) levels were obtained from medical notes. RESULTS: Measures of relationship quality significantly contributed to the explanation of two outcomes: personal integration of diabetes and satisfaction with the burden of self-management behaviours. More specifically, the findings demonstrate that a specific aspect of relationship quality--intimacy in recreational activities--is positively associated with the outcomes mentioned above. CONCLUSIONS: People with Type 2 diabetes who are not taking insulin, who share engagement in physical activities with their partner are more likely to be psychologically well-adjusted to their diagnosis of diabetes.

Hospital-based needlestick use and injuries by Dublin interns in 2010.

BACKGROUND: Needlestick injuries (NSI) remain an occupational hazard for doctors. Previous reports suggested that needlestick practice among interns could be improved. AIMS: We aimed to report the current occupational sharp practice and experience amongst a modern cohort of Irish interns. METHODS: A self-designed questionnaire was distributed among interns at two Dublin-based teaching hospitals. RESULTS: Thirty-one interns completed a self-designed questionnaire. Notably, only 26% routinely wore gloves when performing phlebotomy like tasks; 35% considered their training adequate; 26% had suffered a NSI within the first 8 months of work--over half occurred between 0000 and 0800 hours. There was a higher rate of reporting NSI than in historical reports. CONCLUSION: Improvements have been made in occupational health management of NSI. However, practical preparation for internship continues to remain a concern. Efforts are needed to reduce unnecessary risk of suffering a NSI among our junior doctors.