Association between maternal blood lipids during pregnancy and offspring growth trajectories in a predominantly macrosomic cohort: findings from the ROLO longitudinal birth cohort study.

The purpose of this study is to examine associations between maternal lipid profiles in pregnancy and offspring growth trajectories in a largely macrosomic cohort. This is a secondary analysis of the ROLO birth cohort (n = 293), which took place in the National Maternity Hospital, Dublin, Ireland. Infants were mostly macrosomic, with 55% having a birthweight > 4 kg. Maternal mean age was 32.4 years (SD 3.9 years), mean BMI was 26.1 kg/m2 (SD 4.4 kg/m2) and 48% of children born were males. Total cholesterol, high density lipoprotein cholesterol (HDL-cholesterol), low density lipoprotein cholesterol (LDL-cholesterol) and triglycerides were measured from fasting blood samples of mothers at 14 and 28 week gestation. The change in maternal lipid levels from early to late pregnancy was also examined. Offspring abdominal circumference and weight were measured at 20- and 34-week gestation, birth, 6 months, 2 years and 5 years postnatal. Linear spline multilevel models examined associations between maternal blood lipid profiles and offspring growth. We found some weak, significant associations between maternal blood lipids and trajectories of offspring growth. Significant findings were close to the null, providing limited evidence. For instance, 1 mmol/L increase in maternal triglycerides was associated with faster infant weight growth from 20- to 34-week gestation (0.01 kg/week, 95% CI - 0.02, - 0.001) and slower abdominal circumference from 2 to 5 years (0.01 cm/week, 95% CI - 0.02, - 0.001). These findings do not provide evidence of a clinically meaningful effect.    Conclusion: These findings raise questions about the efficacy of interventions targeting maternal blood lipid profiles in pregnancies at risk of macrosomia. New studies on this topic are needed. What is Known: • Maternal fat accumulation during early pregnancy may potentially support fetal growth in the third trimester by providing a reserve of lipids that are broken down and transferred to the infant across the placental barrier. • There are limited studies exploring the impact of maternal lipid profiles on infant and child health using growth trajectories spanning prenatal to postnatal life. What is New: • Maternal blood lipid profiles were not associated with offspring growth trajectories of weight and abdominal circumference during pregnancy up to 5 years of age in a largely macrosomic cohort, as significant findings were close to the null, providing limited evidence for a clinically meaningful relationship. • Strengths of this work include the use of infant growth trajectories that span prenatal to postnatal life and inclusion of analyses of the change of maternal lipid levels from early to late pregnancy and their associations with offspring growth trajectories from 20-week gestation to 5 years of age.

Effect of supplement crude protein concentration on milk production over the main grazing season and on nitrogen excretion in late-lactation grazing dairy cows.

The objectives of this study are to evaluate the effects of (1) a potential interaction between supplement crude protein (CP) concentration and differing cow genotypes on milk production, (2) differing cow genotypes on milk production, and (3) decreasing the supplement CP concentration on milk production and N excretion during the main grazing season within a spring-calving herd. A 2 × 2 factorial arrangement experiment, with 2 feeding strategies [14%; n = 30 (lower CP; LCP) and 18%; n = 28 (higher CP; HCP) CP concentrate supplements] offered at varying levels according to pasture availability and days in milk (DIM) was conducted over the main grazing season from April 3 to September 3, 2019, at University College Dublin Lyons Farm. Cows were also grouped into 2 genotype groups: lower milk genotype; n = 30 [LM; milk kg predicted transmitting ability (PTA): 45 ± 68.6 (mean ± SD); fat kg PTA: 10 ± 4.9; and protein kg PTA: 7 ± 2.3] and higher milk genotype; n = 28 [HM; milk kg PTA: 203 ± 55.0; fat kg PTA: 13 ± 3.8; and protein kg PTA: 10 ± 2.4]. A total of 46 multiparous and 12 primiparous (total; 58) Holstein Friesian dairy cows were blocked on parity and balanced on DIM, body condition score, and Economic Breeding Index. Cows were offered a basal diet of grazed perennial ryegrass pasture. The N partitioning study took place from August 25 to 30, 2019 (187 ± 15.2 DIM). No interactions were observed for any milk production or milk composition parameter. No effect of supplement CP concentration was observed for any total accumulated milk production, daily milk production, or milk composition parameter measured. The HM cows had increased daily milk yield (+1.9 kg), fat and protein (+0.15 kg), and energy-corrected milk (+1.7 kg), compared with the LM cows. Furthermore, HM cows had decreased milk protein concentration (-0.1%) compared with LM cows. For the N partitioning study, cows offered LCP had increased pasture dry matter intake (PDMI; +0.9 kg/d), dietary N intake (+0.022 kg/d), feces N excretion (+0.016 kg/d), and decreased N partitioning to milk (-2%), and N utilization efficiency (-2.3%). In conclusion, offering cows LCP had no negative influence on milk production or milk composition over the main grazing season where high pasture quality was maintained. However, any potential negative effects of offering LCP on milk production may have been offset by the increased PDMI. Furthermore, offering cows LCP decreased N utilization efficiency due to the higher PDMI and feed N intake associated with cows on this treatment in our study.

Management referral triaging process pilot study: a 'telephone first' approach.

BACKGROUND: In this Occupational Health Department (OHD), a 'telephone first' approach was introduced to triage management referrals with potential to convert to Telephone Independent Medical Assessment (TIMA). Telephone consultation has been widely used in the UK's NHS in the occupational health setting. AIMS: To evaluate TIMA effectiveness and efficiency of OHD resources; comparing the outcome of a triage call compared to previous default allocation of next available appointment, percentage of telephone triage calls converted to TIMA and appointment waiting times. To assess use of OHD resources arising from TIMA. To evaluate service user satisfaction following TIMA. To examine service user characteristics. METHODS: As management referrals were received, service users were given a telephone contact. Data were collected and anonymized regarding service users, who also consented to receive feedback questionnaire. Cross-sectional analysis of this management referral cohort was carried out. RESULTS: Two hundred and sixty-one management referrals were received in the specified period. Eighty per cent had a TIMA carried out (n = 208); 64% of management referrals with TIMA had a report issued (n = 166). Response rate to feedback questionnaire was 38% (n = 70); 94% of survey participants found TIMA acceptable going forward for management referrals (n = 66). CONCLUSIONS: Introduction of a 'telephone first' approach resulted in improved efficiency of this OHD, allowing maximum workforce planning, and positive service user feedback.

Peer review audit of non-specialist occupational physician reports.

BACKGROUND: With declining specialist occupational physician (OP) numbers, there is increasing recognition of the importance of non-specialist physicians in occupational health (OH) service delivery, yet to date, this physician group remains understudied and their competency requirements poorly understood. AIMS: To evaluate the quality of a sample of non-specialist OH reports and compare these with specialist reports. METHODS: A retrospective peer review audit of a convenience sample of 200 consecutive non-specialist and specialist OH reports from an Irish OH service using an assessment form based on the modified Sheffield Assessment Instrument for Letters SAIL(OH)1. RESULTS: Of the 200 peer reviewed OH reports, 159 (80%) were from non-specialists. For all questions, 87% and above of non-specialist reports were 'satisfactory' or 'above expected'. On the overall assessment, out of 10, the mean non-specialist report score was 6.8 (standard deviation (SD) 3-10) and the specialist score was 7.3 (SD 3-10). Comparatively, non-specialist reports highlighted legal/ethical issues marginally more and adhered slightly better to contractual/ethical/legal boundaries, while specialist reports fared better in addressing manager's questions, in their structure and clarity and in covering all significant aspects of the case, particularly if the case was complex. CONCLUSIONS: Our findings demonstrate a high standard of OH report quality in this sample of non-specialist OPs that is consistent across all key OH report components. Potential development areas are also identified that can inform education/training tailored to this physician group and assist in competency standard-setting.

Grey-scale silicon diffractive optics for selective laser ablation of thin conductive films.

Laser beam shaping can play a crucial role in improving many laser processes, especially in selective laser patterning of thin films for display devices and solar cells. Typical Gaussian spatial energy distributions can increase damage to the substrate and lead to large crater edge ridges, which are sub-optimal for typical industrial thin film processes. We report on the design, fabrication, and testing of reflective silicon diffractive optics developed for spatial beam shaping at a wavelength of 355 nm. The application of the elements for laser-selective removal of 20 nm indium tin oxide thin films on glass substrates is demonstrated. The design of the phase profile is first generated using the numerical method of computer-generated holography. The phase profiles are realized on a silicon substrate using a novel two-step fabrication technique consisting of a calibrated focused ion beam and an inductively coupled plasma etch. This results in truly grey-scale, blazed diffractive optics, which were analyzed using white light interferometry and atomic force microscopy. Using the diffractive elements with 355 nm nanosecond pulses shows excellent focused spot profiles with a good reproduction of the intended design with a first-order off-axis diffractive efficiency of approximately 80% at a 45 deg angle of incidence.

The evolving course of HNF4A hyperinsulinaemic hypoglycaemia--a case series.

BACKGROUND: Hepatocyte nuclear factor 4 alpha (HNF4A) gene mutations have a well-recognized role in maturity-onset diabetes of the young and have recently been described in congenital hyperinsulinism. A biphasic phenotype has been postulated, with macrosomia and congenital hyperinsulinism in infancy, and diabetes in young adulthood. In this case series, we report three children with HNF4A mutations (two de novo) and diazoxide-responsive congenital hyperinsulinism, highlighting the potential for ongoing diazoxide requirement and the importance of screening for these mutations even in the absence of family history. CASE REPORTS: All patients presented with macrosomia (mean birthweight 4.26 kg) and hyperinsulinaemic hypoglycaemia soon after birth (median age 1 day). All three (age range 7 months to 11 years 10 months) remain on diazoxide therapy, with dose requirements increasing in one patient. There was no prior family history of diabetes, neonatal hypoglycaemia or macrosomia. Parents were screened for HNF4A mutations post-diagnosis and one father was subsequently found to have maturity-onset diabetes of the young. CONCLUSIONS: This case series follows the evolving course of three patients with confirmed HNF4A-mediated congenital hyperinsulinism, highlighting (1) the variable natural history of these mutations, (2) the potential for prolonged diazoxide requirement, even into adolescence, and (3) the need for screening, regardless of family history.

An unusual lung mass post stem cell transplantation.

We report a case of Mycobacterium kansasii presenting as an obstructing endobronchial mass in a patient post stem cell transplant. The patient had a complete clinical, microbiological, and radiological response to anti-tuberculous treatment. To our knowledge, this is the first case of M. kansasii presenting post transplant with an obstructing lung mass simulating relapse or post-transplant lymphoma.

Use of colour duplex ultrasound as a first line surveillance tool following EVAR is associated with a reduction in cost without compromising accuracy.

INTRODUCTION: CT scanning remains the postoperative surveillance imaging modality of choice following EVAR. Concerns regarding cost, exposure to ionising radiation and intravenous contrast have led to a search for a less expensive, equally efficacious and safer method of monitoring EVAR patients after endograft deployment. This study evaluated the cost saving obtained if CDUS was employed as a first line surveillance tool following EVAR, as well as comparing the two entities in terms of efficacy. PATIENTS & METHODS: Postoperative surveillance CTs and CDUS scans in the 145 patients who have undergone EVAR from 1st June 2003 to 1st July 2010 were compared for the detection of endoleak and determination of residual sac size. RESULTS: Adopting a protocol where CDUS was employed as the first line surveillance tool following EVAR would result in a reduction in the number of postoperative CTs required in 2010 from 235 to 36. Based on 2010 costings, this would equate to an estimated reduction in expenditure from €117,500 to €34,915 a saving of €82,585. CDUS had a sensitivity of 100% and a specificity of 85% in the detection of endoleaks compared to CT. The positive predictive value was 28% and negative predictive value 100%. The Pearson Coefficient correlation of 0.96 indicates a large degree of correlation between CDUS and CT when measuring residual aneurysm size following EVAR. CONCLUSION: CDUS can replace CT as the first line surveillance tool following EVAR. This is associated with a significant reduction in the cost of surveillance without any loss of imaging accuracy.

The effectiveness of exercise interventions to increase physical activity in Cystic Fibrosis: A systematic review.

Physical activity (PA) and exercise have numerous benefits in Cystic Fibrosis (CF) including improved lung function, exercise capacity and quality of life. Despite these benefits, the effectiveness of interventions to promote PA in this population are still largely unknown. The objective of this review was to synthesise existing research and determine whether exercise interventions are effective in promoting PA in people with CF. Using the PRISMA guidelines, a comprehensive search was conducted. Fifteen studies (463 participants) met the inclusion criteria. Eleven studies demonstrated improvements in PA in both short- and long-term interventions. However, the interventions were variable across the included studies, with a large inconsistency in PA assessment tools used. Aerobic training and activity counselling were the two elements identified in this review which most consistently improved PA. Future research should consider larger sample sizes and the use of accurate instruments to assess and track PA levels longitudinally.

Outcomes of point-of-care testing for influenza in the emergency department of a tertiary referral hospital in Ireland.

BACKGROUND: Seasonal influenza causes significant morbidity and mortality, and represents a recurring financial burden for community- and hospital-based treatment. Nosocomial outbreaks exacerbate the impact of influenza. Rapid diagnosis of influenza has been shown to reduce transmission. However, point-of-care testing (POCT) in emergency departments and prudent direction of patients with the virus to reduce hospital-acquired infection (HAI) have not been evaluated widely. AIM: To assess performance characteristics of the Abbott ID NOW™ Influenza A & B 2 system, impact on incidence of hospital-acquired influenza, and admission rate ratio for patients who have POCT compared with laboratory testing. POCT was introduced in the 2018-2019 influenza season. Data from then were compared with preceding and subsequent seasons. METHODS: Records of POCT and laboratory testing for the 2017-2018, 2018-2019, and 2019-2020 influenza seasons were analysed. Sensitivity and specificity of POCT were compared pairwise with Xpert Flu A/B/RSV. Patient admission rates and time of waiting for admission were compared. FINDINGS: Compared to laboratory assay, POCT demonstrated sensitivity of 90.6% (95% confidence interval (CI): 78.6-96.5) and specificity of 99.2% (95.2-100) for influenza A, with 51.4% and 41.9% reductions in numbers of HAIs observed in the two seasons when POCT was available, respectively. The admission rate ratio for influenza cases diagnosed by POCT compared with laboratory diagnosis was 0.72 (95% CI: 0.53-0.97; P = 0.031). CONCLUSION: POCT for influenza appears a feasible strategy for testing of patients during peak influenza virus season, with potential to reduce HAI. The relatively rapid turnaround time may also benefit clinical management of patients presenting at emergency departments with suspected influenza.

Lipid resuscitation in a carnitine deficient child following intravascular migration of an epidural catheter.

A child with cerebral palsy and carnitine deficiency developed ventricular arrhythmias with loss of cardiac output during elective surgery under general anaesthesia with concomitant epidural analgesia. Sinus rhythm was restored on administration of adrenaline, but hypotension persisted despite resuscitation. Bolus administration of 0.8 ml*kg(-1) (20 ml) lipid emulsion resulted in rapid improvement in cardiac output. Blood samples taken before and after the lipid bolus did not demonstrate toxic concentrations of bupivacaine. This case suggests that carnitine deficiency may increase susceptibility to bupivacaine cardiotoxicity.

Structured opioid-free protocol following outpatient hypospadias repair - A prospective SQUIRE 2.0-compliant quality improvement initiative.

BACKGROUND: Prescription opioids have been extensively to manage postoperative pain in children. A growing body of evidence from the adult literature, suggests however, that healthcare providers may be prescribing far more opioids than required, with some studies demonstrating equivalent post-operative pain and clinical outcomes with their omission. OBJECTIVE: The objectives of this prospective study were to assess the current heterogeneity of practice in post-operative opioids prescription following day case hypospadias surgery, to establish a streamlined discharge protocol, and to reduce the use of post-operative opioid prescription by 30% within a 4 month period through the use of systemic forcing functions and education. STUDY DESIGN: This prospective study was approved by the Quality Improvement (QI) sub-committee of the hospital's Research and Ethics Board (REB) and was compliant with the Standards for Quality Improvement Reporting Excellence (SQUIRE 2.0) guidelines. Recruited parents (n = 84) were contacted for telephone interview following a combined intervention of education and omission of post-operative opioids from the discharge prescription. A mixture of qualitative and quantitative techniques were employed including an initial process analysis to assess current opioid use, the creation of balancing measures, and the creation of Plan-Do-Study-Act cycles. Age, procedure, post-operative outcomes and opioid prescription data were recorded over a period of 6 months in 2019. RESULTS: Initial measures in our process analysis demonstrated significant institutional practice variation amongst our 84 post-intervention patients. Our process and fidelity measures confirmed 100% information provision. Following the point of intervention, there was a significant and sustained drop in opioid prescription, with an absolute reduction of 35%, and a relative reduction of 56%. There was no significant difference in patient age, pain scores, or outcomes pre- and post-intervention. DISCUSSION: We have shown in this study that a sustainable decrease in post-operative opioid prescriptions following hypospadias surgery is possible. We managed to achieve a relative reduction 56% which is comparable to other specialties, however, did it within a quality improvement framework to ensure fidelity and no adverse balancing measures. We also managed to reduce the number of doses prescribed in those receiving opioids post-intervention at week 9. CONCLUSION: Our study demonstrates opioids can be safely omitted in hypospadias cohorts without any adverse clinical outcomes or balancing measures. We recommend that opioids be used extremely judiciously in this population in order to minimize exposure in children.

Fetal Growth Trajectories and Their Association with Maternal, Cord Blood, and 5-year Child Adipokines.

BACKGROUND: The growth of the fetus is a complex process influenced by multiple factors. Studies have highlighted the important role of biochemical growth markers such as leptin and adiponectin on fetal growth. OBJECTIVE: To compare fetal growth trajectories with biochemical growth markers from maternal blood samples at 28 weeks' gestation, cord blood samples at birth, and in child blood samples at 5 years of age from mother-infant pairs who were part of the longitudinal ROLO study. METHODS: 781 mother-infant pairs from the ROLO and ROLO Kids study were included. Ultrasound measurements and birth weight were used to develop fetal growth trajectory groups for estimated abdominal circumference and estimated weight. Blood serum levels of leptin, adiponectin, insulin, TNF-alpha, and IL-6 from maternal, cord, and 5-year child samples were recorded. ANOVA and chi-square tests were applied to test the associations between fetal growth trajectory membership and maternal and child biochemical growth indicators. The influence of child sex was also investigated. RESULTS: Male sex was associated with a faster weight trajectory compared to females (p=0.001). At 28 weeks' gestation, maternal leptin levels were significantly higher in mothers with a fetus on a slower estimated abdominal circumference trajectory compared to fast (25616 [IQR: 11656.0 to 35341.0] vs. 14753.8 [IQR: 8565.4 to 24308.1], p < 0.001) and maternal adiponectin levels were lower in fetuses on a slower estimated abdominal circumference trajectory compared to a fast trajectory (22.4 [IQR: 13.6 to 35.9] vs. 27.6 [IQR: 17.6 to 46.3], p=0.027). No associations were noted with inflammatory markers. No associations were identified between fetal growth trajectories and growth markers at 5 years of age. CONCLUSIONS: This study shows that male sex is associated with an accelerated estimated weight trajectory. Furthermore, high leptin and low adiponectin in maternal serum in late gestation are associated with a slower fetal growth trajectory. No associations were identified with blood growth markers after pregnancy.

Mumps epidemiology in the mid-west of Ireland 2004-2008: increasing disease burden in the university/college setting.

Mumps is a contagious vaccine-preventable viral disease that is experiencing a revival in students attending second and third level colleges. Large mumps outbreaks have been reported in several countries despite the presence of childhood immunisation programmes over many years, including measles, mumps, and rubella (MMR) vaccination. In 2008, 1,377 cases of mumps were notified in Ireland and 1,734 in the first three months of 2009 (provisional data). This paper reviews the recent epidemiology of mumps in the Mid-West region of Ireland and highlights preventive measures. A substantial proportion of cases were not laboratory-confirmed and it is important that doctors continue to notify suspected cases. In the Irish Mid-West, data from enhanced surveillance shows a high proportion of mumps in the age group 15-24 years. Complications were uncommon and rarely severe. Where data were available, over half of the cases did not recall having received two doses of MMR, but most recalled one dose. Parents should continue to ensure children receive both MMR vaccinations so that uptake is optimal for protection. Steps were taken to increase awareness of the disease in the school, college and university settings. Preventive measures implemented to limit mumps transmission in the school/college setting over recent years included vaccination of close contacts, isolation for five days and hand hygiene.

Endovascular management of thoracic aortic pathology.

BACKGROUND: Endovascular technology has revolutionised the management of abdominal aortic aneurysmal disease but the less frequent occurrence of pathology in the thoracic aorta has meant that evidence demonstrating the primacy of endovascular treatment strategies in this portion of the vessel is less convincing. Herein we summarise the best available evidence to date. METHODS: A comprehensive search of the surgical and radiological literature using the search term 'endovascular thoracic aorta' was conducted. FINDINGS AND CONCLUSIONS: The vast majority of patients treated by thoracic aortic stent grafting have had their treatment outside the context of a randomised trial. While it would seem that endovascular repair is the treatment of choice for the thoracic aorta, the present evidence is based on single centre case series and is anecdotal at best.

Quantifying the effects of melittin on liposomes.

Melittin, the soluble peptide of bee venom, has been demonstrated to induce lysis of phospholipid liposomes. We have investigated the dependence of the lytic activity of melittin on lipid composition. The lysis of liposomes, measured by following their mass and dimensions when immobilised on a solid substrate, was close to zero when the negatively charged lipids phosphatidyl glycerol or phosphatidyl serine were used as the phospholipid component of the liposome. Whilst there was significant binding of melittin to the liposomes, there was little net change in their diameter with melittin binding reversed upon salt injection. For the zwitterionic phosphatidyl choline the lytic ability of melittin is dependent on the degree of acyl chain unsaturation, with melittin able to induce lysis of liposomes in the liquid crystalline state, whilst those in the gel state showed strong resistance to lysis. By directly measuring the dimensions and mass changes of liposomes on exposure to melittin using Dual Polarisation Interferometry, rather than following the florescence of entrapped dyes we attained further information about the initial stages of melittin binding to liposomes.

Twice-daily variable insulin regimens: proportions of insulin types have little impact on glycaemic control in primary school-aged children.

AIM: To ascertain the relationship between glycaemic outcome and proportions and timing of insulin admixture in a cohort of primary school-aged children who were receiving insulin in a twice-daily regimen. METHODS: Children aged 4-10 years with Type 1 diabetes of > 2 years duration and on twice-daily variable insulin regimens were eligible for inclusion in this study, which took place over a 12-month period. Characteristics of insulin regimen [total daily dose (TDD), proportion of total daily dose given in the morning and proportion of the TDD given as intermediate-acting insulin] were compared with parameters of glycaemia including glycated haemoglobin (HbA(1c)) and continuous glucose monitoring measures (mean glucose, per cent time in various glycaemic ranges, and intra- and inter-day glycaemic variation). RESULTS: Forty-nine children completed the study. Participants were all prepubertal at the start of the study and representative of the local diabetes population aged 4-10 years (mean age 8.2 years, mean duration of diabetes 3.5 years, mean HbA(1c) 8.1%). The mean TDD was 0.9 units/kg/day (range 0.6-1.3). The TDD, percentage of TDD given as intermediate-acting insulin and the percentage of TDD given as the morning dose were not associated with HbA(1c), mean continuous glucose monitoring system glucose, per cent time in various glycaemic ranges or intra- and inter-day glycaemic variation. CONCLUSIONS: Insulin proportions in twice-daily, variable insulin regimens are not associated with any short- or medium-term glycaemic outcomes.

Fatal peri-operative acute tumour lysis syndrome precipitated by dexamethasone.

A 3-year-old patient presented for elective adenotonsillectomy to treat symptomatic obstructive sleep apnoea. The patient had not been assessed at a pre-operative anaesthesia clinic but had undergone uneventful general anaesthesia twice in the previous two years. An uneventful operative course was complicated by the development of clinical instability over the first 6 h postoperatively culminating in cardiorespiratory arrest. Subsequent investigation demonstrated the acute development of tumour lysis syndrome in the setting of a new onset, undiagnosed acute leukaemia. The patient died on the third postoperative day. The use of dexamethasone for prophylaxis against postoperative nausea and vomiting was the likely aetiology of the acute tumour lysis syndrome in this case. This is the first documented peri-operative death due to tumour lysis syndrome after administration of dexamethasone. We discuss the various problems encountered with this case and review the recent literature and case reports on tumour lysis syndrome in the operating theatre.