Maternal intentions towards infant sleeping practices in Ireland.

AIM: Mortality from Sudden Infant Death Syndrome (SIDS) has reduced by 50%-85% globally. Despite improvements from 1990 to 2009, the Irish SIDS rate has plateaued. Reasons for this are unclear, but may be related to a reduced parental SIDS awareness. Our study aimed to assess intentions regarding infant sleeping practices in mothers in Ireland. METHODS: A cross-sectional survey of post-partum mothers was performed in the Rotunda Hospital over a four month period. Mothers with a history of SIDS, miscarriage or neonatal admissions were excluded. RESULTS: Of 451 participants, unsafe sleeping positions were intended by 15.4%, reduced by Irish ethnicity [AOR = 0.52, 95% CI = 0.277-0.959, P = .036]. Safe sleep locations were intended by 66%, increased by Irish ethnicity [AOR = 2.6, 95% CI = 1.617-4.191, P < .001], and reduced by young maternal age [AOR = 0.15, 95% CI = 0.03-0.713, P = .02]. Maternal smoking was more likely in mothers with lower educational level [AOR = 3.51, 95% CI = 1.169-10.56, P = .03]. Soft bedding use was intended by 34.8%, increased in younger mothers [AOR = 2.28, 95% CI = 1.04-4.98, P = .04]. Breastfeeding was intended by 72.2%, decreased by Irish ethnicity [AOR = 0.14, 95% CI = 0.067-0.271, P < .001], and low maternal education [AOR = 0.22, 95% CI = 0.117-0.406, P < .001]. CONCLUSION: Educational campaigns on safe sleep for infants in Ireland need to address modifiable SIDS risks factors, focusing on younger, non-Irish mothers, with lower educational attainment.

Modelling the long-term benefits of tolvaptan therapy on renal function decline in autosomal dominant polycystic kidney disease: an exploratory analysis using the ADPKD outcomes model.

BACKGROUND: The short-term efficacy of tolvaptan in patients with autosomal dominant polycystic kidney disease (ADPKD) has been demonstrated across several phase 3 trials, while the ADPKD Outcomes Model (ADPKD-OM) represents a validated approach to predict natural disease progression over a lifetime horizon. This study describes the implementation of a tolvaptan treatment effect within the ADPKD-OM and explores the potential long-term benefits of tolvaptan therapy in ADPKD. METHODS: The effect of tolvaptan on ADPKD progression was modelled by applying a constant treatment effect to the rate of renal function decline, consistent with that observed in the Tolvaptan Efficacy and Safety in Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes trial (TEMPO 3:4; ClinicalTrials.gov identifier NCT00428948 ). Predictions generated by the ADPKD-OM were compared against aggregated data from a subsequent extension trial (TEMPO 4:4; ClinicalTrials.gov identifier NCT01214421 ) and the Replicating Evidence of Preserved Renal Function an Investigation of Tolvaptan Safety Efficacy in ADPKD trial (REPRISE; ClinicalTrials.gov identifier NCT02160145 ). Following validation, an application of the ADPKD-OM sought to estimate the benefit of tolvaptan therapy on time to end-stage renal disease (ESRD), in a range of ADPKD populations. RESULTS: Model validation against TEMPO 4:4 and REPRISE demonstrated the accuracy and generalisability of the tolvaptan treatment effect applied within the ADPKD-OM. In simulated patients matched to the overall TEMPO 3:4 trial population at baseline, tolvaptan therapy was predicted to delay the mean age of ESRD onset by five years, compared to natural disease progression (57 years versus 52 years, respectively). In subgroup and sensitivity analyses, the estimated delay to ESRD was greatest among patients with CKD stage 1 at baseline (6.6 years), compared to CKD 2 and 3 subgroups (4.7 and 2.7 years, respectively); and ADPKD patients in Mayo subclasses 1C-1E. CONCLUSIONS: This study demonstrated the potential for tolvaptan therapy to delay time to ESRD, particularly among patients with early-stage CKD and evidence of rapidly progressing disease. Data arising from this study highlight the value to be gained by early intervention and long-term treatment with tolvaptan, which may alleviate the economic and societal costs of providing care to patients who progress to ESRD.

Natural products isolated from Tetragonula carbonaria cerumen modulate free radical-scavenging and 5-lipoxygenase activities in vitro.

BACKGROUND: Propolis and cerumen are plant-derived products found in honeybees and stingless bees, respectively. Although propolis is an ancient folk medicine, the bioactivities of cerumen obtained from Australian native stingless bees (Tetragonula carbonaria) have not been widely studied. Therefore, we investigated selected anti-oxidant and anti-inflammatory properties of T. carbonaria cerumen. METHODS: A methanolic extract was prepared from the combined cerumen of 40 T. carbonaria hives, and HPLC was used to screen for chemical constituents that scavenged 2,2-azobis(2-methylpropionamidine) dihydrochloride (AAPH). The ability of cerumen extracts to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and to interfere with leukotriene B4 (LTB4) production in ionomycin-stimulated human neutrophils was also examined. RESULTS: The extract dose-dependently scavenged DPPH (EC50 = 27.0 ± 2.3 µg/mL); and inhibited the 5-lipoxygenase (5-LOX)-mediated oxidation of linoleic acid (IC50 = 67.1 ± 9.6 µg/mL). Pre-treatment of isolated human neutrophils with the methanolic cerumen extract additionally inhibited the ionomycin-stimulated production of LTB4 from these cells (IC50 = 13.3 ± 5.3 µg/mL). Following multi-solvent extraction, the free radical-scavenging and 5-LOX-inhibiting activities of the initial cerumen extract were retained in a polar, methanol-water extract, which contained gallic acid and a range of flavonone and phenolic natural products. CONCLUSIONS: The findings identify free radical scavenging activity, and interference by extracts of T. carbonaria cerumen in 5-LOX-LTB4 signaling. Further investigation is needed to determine whether the extracts will provide therapeutic benefits for medical conditions in which oxidative stress and inflammation are implicated, including cardiovascular disease and impaired wound healing.

Anti-Fibrotic Potential of Tomentosenol A, a Constituent of Cerumen from the Australian Native Stingless Bee, Tetragonula carbonaria.

Bioactivity-guided fractionation was used to isolate two compounds, tomentosenol A (1) and torellianone A (2), from a cerumen extract from Tetragonula carbonaria. The anti-fibrotic activity of these compounds was examined using human cultured neonatal foreskin fibroblasts (NFF) and immortalised keratinocytes (HaCaTs). Tomentosenol A (1), inhibited NFF and HaCaT cell proliferation and prevented NFF and HaCaT scratch wound repopulation at 12.5-25 µM concentrations. These inhibitory effects were associated with reduced cell viability, determined by tetrazolium dye (MTT) and sulforhodamine B (SRB) assays. Compound 1 further inhibited transforming growth factor-ß1 (TGF-ß1)-stimulated, NFF-myofibroblast differentiation and soluble collagen production; and was an effective scavenger of the model oxidant, 2,2-diphenyl-1-picrylhydrazyl (DPPH·), with an EC50 value of 44.7 ± 3.1 µM. These findings reveal significant anti-fibrotic potential for cerumen-derived tomentosenol A (1).

Fatal fetal abnormality Irish live-born survival-an observational study.

The aim of the study was to provide accurate information regarding live-born infant survival after diagnosis of fatal fetal anomaly (FFA) to aid decision-making in respect of pregnancy management, and to ascertain the natural history of live-born infants with FFAs via a retrospective analysis of death records (2006-2018), from the National Paediatric Mortality Registry (source Central Statistics Office 2019). Diagnoses and survival times were ascertained from narrative records with further ascertainment and reconciliation of trisomies 13 and 18 cases by review of cytogenetic test records, the National Death Events Register and National Perinatal Epidemiology Centre data. During the study period, termination of pregnancy was not permitted under the Irish Constitution. Patients are live-born babies with fatal fetal anomalies whose deaths were registered in the Republic of Ireland. The main outcome measure was construction of anomaly-specific survival curves, or survival time range and median for those anomalies with rare occurrence. Survival curves for anencephaly, bilateral renal agenesis, thanatophoric dysplasia, trisomy 13, and trisomy 18 show that 90% (n = 95), 93% (n = 60), 100% (n = 14), 37% (n = 92) and 33% (n = 162), respectively, were deceased by 24 h and 98%, 100%, 100%, 73%, and 53%, respectively, by 1 week post-delivery. Survival time range and median were calculated for triploidy (3.5 h-20 days; 10.5 days), whose occurrence was rare. Anhydramnios, craniorachischisis, hydranencephaly and severe hydrocephalus were extremely rare and all deaths were neonatal deaths. Our results provide 13 years of national natural history data of live birth FFA survival. This provides objective information to aid obstetric counselling of couples upon diagnosis of an FFA.

A retrospective review of the contribution of rare diseases to paediatric mortality in Ireland.

AIMS: To ascertain the number of paediatric deaths (0-14 years) with an underlying rare disease in the Republic of Ireland between the years 2006-2016, and to analyse bed usage by a paediatric cohort of rare disease inpatients prior to in-hospital death. BACKGROUND: Rare diseases are often chronically debilitating and sometimes life-threatening diseases, with the majority (69.9%) of rare diseases being of paediatric onset. The Orphanet database contains information on 6172 unique rare diseases. Under-representation of rare diseases in hospital healthcare coding systems leads to a paucity of rare disease epidemiological data required for healthcare planning. Studies have cited variable incidence rates for rare disease, however the burden of rare diseases to healthcare services still remains unclear. This study represents a thorough effort to identify the percentage of child mortality and paediatric bed usage attributable to rare diseases in the Republic of Ireland, thus addressing a major gap in the rare disease field. METHODS: Retrospective analysis of paediatric death registration details for the Republic of Ireland in the 11-year period 2006-2016 from the National Paediatric Mortality Register. Data was subcategorised as Neonatal (0-28 days), Post Neonatal (29 days < 1 year) and older (1-14 years). Bed usage data (ICD-10 code, narrative and usage) of paediatric inpatients who died during hospitalisation from January 2015 to December 2016 was extracted from the National Quality Assurance Improvement System of in-patient data. Orphacodes were assigned to rare disease cases from ICD-10 codes or diagnostic narrative of both datasets. RESULTS: There were 4044 deaths registered from 2006-2016, aged < 15 years, of these 2368 (58.6%) had an underlying rare disease. Stratifying by age group; 55.6% (1140/2050) of neonatal deaths had a rare disease, 57.8% (450/778) post-neonatal, and 64% (778/1216) of children aged 1-14 years. Mortality coding using ICD-10 codes identified 42% of rare disease cases with the remainder identified using death certificate narrative records. Rare disease patients occupied 87% of bed days used by children < 15 years who died during hospitalisation from January 2015 to December 2016. CONCLUSION: Additional routine rare disease coding is necessary to identify rare diseases within Irish healthcare systems to enable better healthcare planning. Rare disease patients are overrepresented in paediatric mortality statistics and in-patient length of stay during hospital admission prior to death.

Trends in road transport collision deaths in the Irish paediatric population: a retrospective review of mortality data, 1991-2015.

OBJECTIVE: To establish the incidence of road transport collision (RTC) fatalities in the Irish paediatric population, examining trends in fatality rates over a period of 25 years, during which several national road safety interventions were implemented. STUDY DESIGN: Retrospective review of death registration details of children 0-19 years in Ireland between January 1991 and December 2015. Trends in mortality rates were investigated using average annual per cent change and Poisson regression analysis. RESULTS: Proportionate RTC mortality, the majority of which occurred on public roads (94.1%, n=1432) increased with age; <0.3% (<1 year), 8.3% (1-14 years) and 18.4% (15-19 years) (2011-2015 average). Over time, rates declined significantly in all age groups; reductions of 79.0% (4.0 to 0.84/100 000, 1-14 years) and 68.4% (15.5 to 4.9/100 000, 15-19 years) resulted in 537 (95% CI 515 to 566) fewer child deaths (1-19 years) over the period 1996-2015. This reduction was evident for both road user types, the greatest decline (84.8%) among pedestrians 1-14 years (2.1 to 0.32/100 000) and the lowest (66.5%) among occupants 15-19 years, the majority of whom were male (12.4 to 4.2/100 000). The rate of decline was greatest during periods coinciding with introduction of targeted interventions. Risk of death in children 1-14 years was halved in the period after 2002 (incidence rate ratio (IRR) 0.52) while in children 15-19 years old, a significantly lower RTC fatality risk was evident after 2006 and 2010 (IRR 0.68 and IRR 0.50). CONCLUSION: Child and adolescent mortality from RTCs has declined dramatically in Ireland, in excess of reductions in overall paediatric mortality. However, rates remain higher than in other EU countries and further effort is required to reduce the number of deaths further, particularly among adolescent males.

Nutrient deprivation increases vulnerability of endothelial cells to proinflammatory insults.

Nutrient deprivation is a stimulus for oxidative stress and is an established method for induction of cell autophagy and apoptosis. The aims of this study were to identify conditions that evoke superoxide production in cultured human umbilical vein endothelial cells (HUVECs), determine the mechanism of action for this response, and examine whether the stimulus might facilitate the adhesion of human isolated neutrophils to the HUVECs. HUVECs were incubated in M199 medium under conditions of serum starvation (serum-free M199 medium), low serum (medium containing 2% fetal calf serum), and high serum (medium containing 20% fetal calf serum). HUVECs were also incubated under proinflammatory conditions, in medium supplemented with 50ng/ml tumor necrosis factor-α (TNF-α) or neutrophils preactivated with 10nM phorbol 12-myristate 13-acetate (PMA). Superoxide production was increased fourfold in serum-starved HUVECs compared to cells incubated in 20% medium, and this was reduced by inhibitors of the mitochondrial electron transport chain and mitochondrial Ca(2+) uniporter. Superoxide production was 23.6% higher in HUVECs incubated with TNF-α in 2% medium compared to 2% medium alone, but unchanged with TNF-α in 20% medium. PMA-activated neutrophils adhered to morphologically aberrant HUVECs, which were mainly evident under the low-serum condition. The findings show a role of mitochondrial enzymes in superoxide production in response to nutrient deprivation and suggest that proinflammatory responses in HUVECs become manifest when HUVECs are in an already-compromised state.

Sudden unexplained death in childhood (1-4 years) in Ireland: an epidemiological profile and comparison with SIDS.

OBJECTIVE: To examine the incidence of sudden unexplained death in children 1-4 years old (SUDC) in Ireland and to compare the epidemiological profile of SUDC with that of SIDS. DESIGN: All cases of sudden unexplained death in children <5 years in Ireland between 1994 and 2008 were reviewed. Epidemiological information obtained from parental questionnaires and post-mortem reports was examined, and data on cases ≥52 weeks compared with cases <52 weeks. RESULTS: SUDC accounted for 5% (n=44) of deaths in children aged 1-4 years during 1994-2008. During this period, the SIDS rate dropped from 0.71 to 0.34 per 1000 live births, while the SUDC rate increased from 0.08 to 0.18 deaths per 10 000 population aged 1-4 years. The median age of SUDC cases was 71.5 weeks, and the male/female ratio was 1.3:1. All died during a sleep period, 71% between 10pm and 8am, and more than two-thirds were found prone. Fewest cases occurred during July-September (11%), and a greater proportion occurred at weekends (55%). 52% (17/33) had symptoms (any) in the 48 h before death, and 35% (11/31) visited their general practitioner because of illness in the week preceding death. SUDC differed from SIDS in prevalence of maternal smoking (38% vs 72%, p<0.001), bed-sharing (17% vs 49%, p<0.001), and whether found prone (72% vs 23%, p<0.001). CONCLUSION: While SUDC shares some characteristics with SIDS, there are also some important differences. Further data collection will help determine whether SIDS and SUDC represent the same pathophysiological entity. Standardisation of protocols for investigating sudden deaths is urgently required for accurate diagnosis of cases.