Outcomes to 5 years of outborn versus inborn infants <32 weeks in Western Australia: a cohort study of infants born between 2005 and 2018.

OBJECTIVE: We compared mortality and morbidity of inborn versus outborn very preterm infants <32 weeks' gestation in Western Australia (WA) between 2005 and 2018. DESIGN: Retrospective cohort study. PATIENTS: Infants <32 weeks' gestation who were born in WA. MAIN OUTCOME MEASURES: Mortality was assessed as death before discharge home from the tertiary neonatal intensive care unit. Short-term morbidities included combined brain injury (intracranial haemorrhage grade ≥3 and cystic periventricular leukomalacia) and other major neonatal outcomes. Developmental assessments at age 2, 3 and 5 years were evaluated. We performed multivariable logistic regression analysis of outborn status on outcomes, controlling for gestational age, birth weight z-score, sex and multiple birth. RESULTS: A total of 4974 infants were born in WA between 22 and 32 weeks' gestation between 2005 and 2018 of which 4237 (89.6%) were inborn and 443 (10.4%) were outborn. Overall mortality to discharge was higher in outborn infants (20.5% (91/443) vs 7.4% (314/4237); adjusted OR (aOR) 2.44, 95% CI 1.60 to 3.70, p<0.001). Outborn infants had higher rates of combined brain injury than those inborn (10.7% (41/384) vs 6.0% (246/4115); aOR 1.98, 95% CI 1.37 to 2.86), p<0.001). No difference in up to 5-year developmental measures was detected. Follow-up data were available for 65% of outborn and 79% of inborn infants. CONCLUSIONS: Outborn preterm infants <32 weeks in WA had increased odds of mortality and combined brain injury than those inborn. Developmental outcomes up to 5 years were similar between groups. Loss to follow-up may have impacted the long-term comparison.

Time to regain birth weight - a marker to predict the severity of retinopathy of prematurity?

BACKGROUND: Poor weight gain in the first few weeks of life has been studied as a predictor of retinopathy of prematurity (ROP). Our aim was to assess whether time taken to regain birthweight (BW) be used as an additional marker to identify infants with type 1 ROP. METHODS: In this retrospective study, preterm infants (< 27 weeks gestational age at birth) born during the period from 1/1/2010-31/12/2015 at a tertiary neonatal intensive care unit in Australia were included. Twenty-seven preterm infants with Type 1 ROP were identified. Controls (No ROP or ROP other than type 1) were matched with cases on gestational age at birth and BW (1:4 ratio). Data were collected from the database and medical records. RESULTS: The median (IQR) gestational age for Type 1 ROP and control groups were 24 (24-26) and 25 (24-26) weeks respectively and median (IQR) BW for Type 1 ROP and control groups were 675 (635-810) and 773 (666-884) grams respectively. Preterm infants with Type 1 ROP were more likely to be small for gestational age (SGA) (18.5% vs 3.7%, p = 0.015) and had increased weeks on oxygen therapy (median 11.9 vs 9.1, p = 0.028). Time to regain BW was longer in preterm infants with type 1 ROP than controls but did not reach statistical significance (median 9 vs 7 days, OR 1.08, 95% CI 1.00-1.17, p = 0.059) adjusted for SGA and duration of oxygen therapy. The area under the curve from the time to regain BW model with adjustment for SGA and duration of oxygen therapy was 0.73 (95% CI 0.62-0.83). CONCLUSION: We hypothesize that time to regain BW has potential to aid prediction of Type 1 ROP and this warrants further investigation in a larger prospective study.

CD8 T-cell responses against the immunodominant Theileria parva peptide Tp249-59 are composed of two distinct populations specific for overlapping 11-mer and 10-mer epitopes.

Immunity against Theileria parva is associated with CD8 T-cell responses that exhibit immunodominance, focusing the response against limited numbers of epitopes. As candidates for inclusion in vaccines, characterization of responses against immunodominant epitopes is a key component in novel vaccine development. We have previously demonstrated that the Tp249-59 and Tp1214-224 epitopes dominate CD8 T-cell responses in BoLA-A10 and BoLA-18 MHC I homozygous animals, respectively. In this study, peptide-MHC I tetramers for these epitopes, and a subdominant BoLA-A10-restricted epitope (Tp298-106 ), were generated to facilitate accurate and rapid enumeration of epitope-specific CD8 T cells. During validation of these tetramers a substantial proportion of Tp249-59 -reactive T cells failed to bind the tetramer, suggesting that this population was heterogeneous with respect to the recognized epitope. We demonstrate that Tp250-59 represents a distinct epitope and that tetramers produced with Tp50-59 and Tp49-59 show no cross-reactivity. The Tp249-59 and Tp250-59 epitopes use different serine residues as the N-terminal anchor for binding to the presenting MHC I molecule. Molecular dynamic modelling predicts that the two peptide-MHC I complexes adopt structurally different conformations and Tcell receptor ß sequence analysis showed that Tp249-59 and Tp250-59 are recognized by non-overlapping T-cell receptor repertoires. Together these data demonstrate that although differing by only a single residue, Tp249-59 and Tp250-59 epitopes form distinct ligands for T-cell receptor recognition. Tetramer analysis of T. parva-specific CD8 T-cell lines confirmed the immunodominance of Tp1214-224 in BoLA-A18 animals and showed in BoLA-A10 animals that the Tp249-59 epitope response was generally more dominant than the Tp250-59 response and confirmed that the Tp298-106 response was subdominant.

Leadership skills teaching in Yorkshire & the Humber - a survey: uncovering, sharing, developing, embedding.

Medical leadership is a hot topic, but it is not known yet how to teach this most effectively. A working party of educators in Yorkshire and the Humber (Y&H) studied the leadership domains, as set out in the Medical Leadership Competency Framework and from this distilled a set of 'trainable' leadership skills, which were felt to be important to teach during general practitioner (GP) training. A questionnaire was sent out to a large GP educational community (educators and trainees) within Y&H to establish the following: (i) whether the distilled skills were thought to have face validity when applied to the concept of leadership, (ii) what was the relative importance of these skills in relation to each other and (iii) the degree to which these skills were already being taught in practice placements and at General Practice Specialty Training Programme (GPSTP) teaching sessions.Educators reported more teaching and training occurring than trainees reported receiving, and the relative importance of the skills sets were different between educators and trainees. It was evident that leadership skills are currently being taught, but that making training explicitly 'leadership', and raising the importance of leadership skills in GP, may address some of these imbalances. Educators requested guidance on how to teach these skills effectively and commented that many existing opportunities for leadership teaching and training are not well recognised or used. Routinely and regularly offering the chance for trainees at all levels to be exposed to leadership skills by role modelling, making use of everyday opportunities in practice to teach and encouraging trainee involvement in projects and opportunities to practice new skills can facilitate the acquisition and celebration of mastery of generic leadership skills.

A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus.

OBJECTIVE: Failure of closure of the patent ductus arteriosus (PDA) may be associated with harm. Early cardiac ultrasound-targeted treatment of a large PDA may result in a reduction in adverse outcomes and need for later PDA closure with no increase in adverse effects. STUDY DESIGN: Multicentre, double-blind, placebo-controlled randomised trial. SETTING: Three neonatal intensive care units in Australia. PATIENTS AND INTERVENTIONS: Eligible infants born <29 weeks were screened for a large PDA and received indomethacin or placebo before age 12 h. MAIN OUTCOME: Death or abnormal cranial ultrasound. RESULTS: The trial ceased enrolment early due to lack of availability of indomethacin. 164 eligible infants were screened before 12 h; of the 92 infants with a large PDA, 44 were randomised to indomethacin and 48 to placebo. There was no difference in the main outcome between groups. Infants receiving early indomethacin had significantly less early pulmonary haemorrhage (PH) (2% vs 21%), a trend towards less periventricular/intraventricular haemorrhage (PIVH) (4.5% vs 12.5%) and were less likely to receive later open-label treatment for a PDA (20% vs 40%). The 72 non-randomised infants with a small PDA were at low risk of pulmonary haemorrhage and had an 80% spontaneous PDA closure rate. CONCLUSIONS: Early cardiac ultrasound-targeted treatment of a large PDA is feasible and safe, resulted in a reduction in early pulmonary haemorrhage and later medical treatment but had no effect on the primary outcome of death or abnormal cranial ultrasound. REGISTERED TRIAL: Australian New Zealand Clinical Trials Registry (ACTRN12608000295347).

Factors influencing survival in pre-viable preterm premature rupture of membranes.

OBJECTIVE: An observational study of a consecutive case series of pre-viable PPROM (16-24 gestational weeks) was performed between 2001 and 2007 in a single tertiary centre to identify factors that predict neonatal survival. METHODS: Detailed obstetric, ultrasound and neonatal data were abstracted from clinical records. Univariate, multivariate and receiver operator curve (ROC) analyses were performed to identify predictors of neonatal survival to discharge. RESULTS: A total of 143 cases of PPROM were identified. Survival to discharge was less with PPROM at 16-20 weeks than 20-24 weeks (17% versus 39%; p=0.042). GA at PPROM, latency, mode of delivery and electronic foetal monitoring (EFM) were all significant, independent, predictors of survival (p<0.05). Ultrasound assessed amniotic fluid index (AFI) was a poor predictor of survival (area under ROC=0.649, 95% CI=0.532-0.766). A multivariable predictive model, including GA at PPROM, latency, mode of delivery and EFM had an area under the ROC of 0.954 (95% CI=0.916-0.993, sensitivity 97%, specificity 89% and accuracy 92%). CONCLUSION: Pre-viable PPROM has a poor prognosis, though modern neonatal management techniques may improve survival in late pre-viable PPROM. The predictive model generated from this consecutive case series of this rare condition provides valuable data for counselling patients with this condition.