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Abortion is permitted in many jurisdictions after the age at which an infant is viable on the basis of intensive neonatal care techniques. Does this cause special concerns for those involved in perinatal care and termination of pregnancy services or is the overlap mainly an abstract issue fretted over by ethicists and academics? In order to explore this question, a group of clinicians involved in this area of care were interviewed and their interviews analysed using qualitative measures. The clinicians concerned were exercised by the ethical issues and had various ways of resolving them which tended to reflect a gradualist, multifaceted and, to some extent, particularist approach to ethical decision-making in relation to the edges of human life. The ways in which those strands of ethical thought are instanced in the interview material are reported and discussed.

PurposeTo investigate whether the observed international differences in retinopathy of prematurity (ROP) treatment rates within the Benefits of Oxygen Saturation Targeting (BOOST) II trials might have been caused by international variation in ROP disease grading.MethodsGroups of BOOST II trial ophthalmologists in UK, Australia, and New Zealand (ANZ), and an international reference group (INT) used a web based system to grade a selection of RetCam images of ROP acquired during the BOOST II UK trial. Rates of decisions to treat, plus disease grading, ROP stage grading, ROP zone grading, inter-observer variation within groups and intra-observer variation within groups were measured.ResultsForty-two eye examinations were graded. UK ophthalmologists diagnosed treat-requiring ROP more frequently than ANZ ophthalmologists, 13.9 (3.49) compared to 9.4 (4.46) eye examinations, P=0.038. UK ophthalmologists diagnosed plus disease more frequently than ANZ ophthalmologists, 14.1 (6.23) compared to 8.5 (3.24) eye examinations, P=0.021. ANZ ophthalmologists diagnosed stage 2 ROP more frequently than UK ophthalmologists, 20.2 (5.8) compared to 12.7 (7.1) eye examinations, P=0.026. There were no other significant differences in the grading of ROP stage or zone. Inter-observer variation was higher within the UK group than within the ANZ group. Intra-observer variation was low in both groups.ConclusionsWe have found evidence of international variation in the diagnosis of treatment-requiring ROP. Improved standardisation of the diagnosis of treatment-requiring ROP is required. Measures might include improved training in the grading of ROP, using an international approach, and further development of ROP image analysis software.

Objective:To explore population characteristics, organization of health services and comparability of available information for very low birth weight or very preterm neonates born before 32 weeks’ gestation in 11 high-income countries contributing data to the International Network for Evaluating Outcomes of Neonates (iNeo).Study Design:We obtained population characteristics from public domain sources, conducted a survey of organization of maternal and neonatal health services and evaluated the comparability of data contributed to the iNeo collaboration from Australia, Canada, Finland, Israel, Italy, Japan, New Zealand, Spain, Sweden, Switzerland and UK.Results:All countries have nationally funded maternal/neonatal health care with >90% of women receiving prenatal care. Preterm birth rate, maternal age, and neonatal and infant mortality rates were relatively similar across countries. Most (50 to >95%) between-hospital transports of neonates born at non-tertiary units were conducted by designated transport teams; 72% (8/11 countries) had designated transfer and 63% (7/11 countries) mandate the presence of a physician. The capacity of ‘step-down’ units varied between countries, with capacity for respiratory care available in <10% to >75% of units. Heterogeneity in data collection processes for benchmarking and quality improvement activities were identified.Conclusions:Comparability of healthcare outcomes for very preterm low birth weight neonates between countries requires an evaluation of differences in population coverage, healthcare services and meta-data.

Objective:: To examine the relationship between hypertensive disorders of pregnancy (HDPs) and mortality and major morbidities in preterm neonates born at 24 to 28 weeks of gestation. Study Design:: Using an international cohort, we retrospectively studied 27?846 preterm neonates born at 240to 286weeks of gestation during 2007 to 2010 from 6 national neonatal databases. The incidence of HDP was compared across countries, and multivariable logistic regression analyses were conducted to examine the association of HDP and neonatal outcomes including mortality to discharge, bronchopulmonary dysplasia, severe brain injury, necrotizing enterocolitis and treated retinopathy of prematurity. Results:: The incidence of HDP in the entire cohort was 13% (range 11 to 16% across countries). HDP was associated with reduced odds of mortality (adjusted odds ratio (aOR) 0.77; 95% confidence interval (CI) 0.67 to 0.88), severe brain injury (aOR 0.74; 95% CI 0.62 to 0.89) and treated retinopathy (aOR 0.82; 95% CI 0.70 to 0.96), but increased odds of bronchopulmonary dysplasia (aOR 1.16; 95% CI 1.05 to 1.27). Conclusions:: In comparison with neonates born to mothers without HDP, neonates of HDP mothers had lower odds of mortality, severe brain injury and treated retinopathy, but higher odds of bronchopulmonary dysplasia. The impact of maternal HDP on newborn outcomes was inconsistent across outcomes and among countries; therefore, further international collaboration to standardize terminology, case definition and data capture is warranted.

Traditional gentamicin dosing every 8-24 h depending on age and weight in neonates does not provide the ideal concentration-time profile to both optimize the concentration-dependent killing by aminoglycosides and minimize toxicity. Fifty-three neonates were audited prospectively while receiving gentamicin 2.5 mg/kg every 8-24 h, aiming for peak concentrations (Cmax) of 6-10 mg/L and trough concentrations (Cmin) <2 mg/L. After the first dose, the mean (+/- s.d.) Cmax was 5.5 +/- 0.7 mg/L with sub-therapeutic concentrations (<6 mg/L) in 62% of patients, while the mean Cmin was >2 mg/L in 15% of the neonates. After the third dose the Cmax was 7.5 +/- 1.5 mg/L, with 17% <6 mg/L, whereas the mean Cmin was 2.2 +/- 1.1 mg/L with 49% of values >2 mg/L. An extended interval dosing method (24, 36 and 48 h) for infant weights of 0.75-5 kg was developed by simulation, and audited prospectively in 51 neonates. Prospective analysis of the extended interval dosing method showed a mean Cmax after the first dose of 13.1 +/- 3.6 mg/L, while the mean Cmin was 0.7 +/- 0.6 mg/L. Seventy-eight per cent had Cmax of >10 mg/L after the first dose. The mean area under the concentration versus time curve AUC0-24 was 93 mg*h/L (target = 100 mg*h/L). The extended interval dosing achieved higher Cmax values while ensuring that overall exposure per 24 h was acceptable. Prospective testing of the method demonstrated good predictive ability.

Objective: To determine whether pressure-limited intermittent mandatory ventilation with permissive hypercapnia and positive end-expiratory pressure (PEEP) titrated to arterial oxygen tension (PaO2) prevents or reduces acute lung injury, compared to conventional ventilation, in salinelavaged rabbits. Design: Prospective randomised trial. Setting: University animal laboratory. Subjects: 18 New Zealand White rabbits. Interventions: Following five sequential saline lung lavages, anaesthetised rabbits were randomly allocated in pairs to receive either of two ventilation protocols using intermittent mandatory ventilation. The study group had peak inspiratory pressure limited to 15 cm H2O and arterial partial pressure of carbon dioxide (PaCO2) was allowed to rise. The control group received 12 ml/kg tidal volume with rate adjusted for normocarbia. PEEP and fractional inspired oxygen (FIO2) were adjusted to maintain PaO2between 8 and 13.3 kPa (60 and 100 mm Hg) using a predetermined protocol. At 10 h or following death, lung lavage was repeated and lung histology evaluated. Measurements and main results: The mean increase in lavage cell counts and protein concentration and hyaline membrane scores were not significantly different between the groups. Oxygenation progressively improved more in the study group (p=0.01 vs control for PaO2/FIO2ratio and alveolar-arterial oxygen tension gradient (AaDO2)). PEEP was similar and the mean airway pressure higher in the control group, suggesting that this probably resulted from less ventilatorinduced injury in the study group. Four deaths occurred in the control group (three due to pneumothorax and one to hypoxaemia) and none in the study group (p=0.08). Conclusions: This ventilatory protocol may have failed to prevent lung overdistension or it may have provided insufficient PEEP to prevent injury in this model; PEEP greater than the lower inflection point of the pressure-volume curve has been shown to prevent injury almost entirely.

AIMS: To examine cognitive, behavioural, and educational outcomes in middle childhood among a birth cohort of very low birthweight children. METHODS: Two hundred and ninety eight survivors from a national birth cohort of 413 New Zealand very low birthweight (VLBW) children born in 1986 were assessed at 7 to 8 years of age on measures of behaviour, cognitive ability, school performance and the need for special education. These outcomes were compared with the same measures in a general population sample of over 1000 children studied at a similar age. RESULTS: The VLBW children had significantly higher rates of problems and poorer levels of functioning across all outcome measures than the general child sample. These differences persisted even after control for variability in social, family, and other characteristics of the two samples and for the degree of sensorineural disability. There was evidence of a gradient of risk with birthweight, with extremely low birthweight children having generally higher rates of problems and difficulties than other VLBW children after covariate control. CONCLUSIONS: The findings are consistent with a growing body of research evidence which suggests that premature and VLBW infants are at increased risk of longer term morbidity and functional impairment in middle childhood.

Compte tenu de l’existence répandue des croyances délétères relatives au mal de dos [1,2]et des limites des questionnaires existant, le « back pain attitudes questionnaire(Back-PAQ) » a récemment été développé pour mieux les identifier [3]. L’objectif de cette étude était de traduire en français la version courte (10 items) de ce questionnaire et d’évaluer les qualités psychométriques de cette nouvelle version (le Back-PAQ-Fr).

Introduction: Neonatal sepsis is a major cause of morbidity and mortality despite antibiotic treatment. Effective adjunctive treatments are needed. Newborn infants are relatively deficient in IgG. Meta-analyses of trials of intravenous IgG for suspected or proven neonatal sepsis suggest reduced all cause mortality but the trials are small and some are of poor quality.Hypothesis: In newborn infants receiving antibiotics for clinical sepsis, the addition of polyclonal intravenous immunoglobulin IgG (IVIG) therapy reduces mortality and major morbidity compared with antibiotics alone.Methods: Infants receiving antibiotics for proven or suspected serious infection were randomized to receive either two infusions of IVIG 500mg/kg (10ml/kg) or two infusions of matching placebo (0.2% albumin solution, 10ml/kg) 48 hours apart.Outcome measures: The primary outcome was mortality or major disability at two years corrected for gestational age.Preliminary results:The 2 groups were well balanced in all prognostic variables.IVIG (n=1759), Placebo (n= 1734)All babiesPrimary outcome IVIG 691 (39.3%), Placebo 682 (39.3%), RR 1.0 (0.86,1.16)Mortality at 2yrs IVIG 317 (18%), Placebo 304 (17.5%), RR 1.03 (0.89-1.19)SurvivorsDisability at 2yrs IVIG 374 (25.9%), Placebo 378 (26.4%), RR 0.98 (0.87-1.11)Conclusions: Intravenous immunoglobulin therapy had no effect on the outcomes of suspected or proven neonatal sepsis. This trial is substantially larger (n=3,493) than all the other trials in the previous meta-analysis combined (n=378) and illustrates the importance of large pragmatic trials in establishing the role of emerging treatments before their widespread introduction on the basis of potentially unreliable evidence.

A NUMBER of investigations have been made of the physical and chemical adsorption of both liquids and gases on silica gel1. In particular, Kiselev2has examined the nature of the adsorbed complex formed by a number of gases including water and methanol. However, no rate data are available on either the adsorption or desorption process.

Abstract: Extreme value theory is used to derive asymptotically motivated models for unusual or rare events, e.g. the upper or lower tails of a distribution. A new flexible extreme value mixture model is proposed combining a non-parametric kernel density estimator for the bulk of the distribution with an appropriate tail model. The complex uncertainties associated with threshold choice are accounted for and new insights into the impact of threshold choice on density and quantile estimates are obtained. Bayesian inference is used to account for all uncertainties and enables inclusion of expert prior information, potentially overcoming the inherent sparsity of extremal data. A simulation study and empirical application for determining normal ranges for physiological measurements for pre-term infants is used to demonstrate the performance of the proposed mixture model. The potential of the proposed model for overcoming the lack of consistency of likelihood based kernel bandwidth estimators when faced with heavy tailed distributions is also demonstrated. [Copyright &y& Elsevier]