different population groups to ensure public health campaigns remain responsive to community vaccine sentiments. Given the potential impact of vaccine hesitancy on the required population herd immunity threshold, we need to understand the attitudinal and behavioural drivers in order to inform community-led communication strategies to build trust and optimise COVID-19 vaccine uptake.We declare no competing interests.

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Objective: To identify risk factors associated with mortality in critically ill children requiring continuous renal replacement therapy. Design: Retrospective observational study based on a prospective registry. Setting: Tertiary and quaternary referral 30-bed PICU. Patients: Critically ill children undergoing continuous renal replacement therapy were included in the study. Interventions: Continuous renal replacement therapy. Measurements and Main Results: Overall mortality was 36% (n = 58) among the 161 patients treated with continuous renal replacement therapy during the study period and was significantly higher in patients on extracorporeal membrane oxygenation (47.5%, 28 of 59) than in patients not requiring extracorporeal membrane oxygenation (28.4%, 29 of 102; p = 0.022). According to the admission diagnosis, we found the highest mortality in patients with onco-hematologic disease (77.8%) and the lowest in patients with renal disease (5.6%). Based on multivariate logistic regression analysis, the presence of higher severity of illness score at admission (adjusted odds ratio, 1.49; 95% CI, 1.18–1.89; p < 0.001), onco-hematologic disease (odds ratio, 17.10; 95% CI, 4.10–72.17; p < 0.001), fluid overload 10%–20% (odds ratio, 3.83; 95% CI, 1.33–11.07; p = 0.013), greater than 20% (odds ratio, 15.03; 95% CI, 4.03–56.05; p < 0.001), and timing of initiation of continuous renal replacement therapy (odds ratio, 1.01; 95% CI, 1.00–1.01; p = 0.040) were independently associated with mortality. In our population, the odds of dying increases by 1% for every hour of delay in continuous renal replacement therapy initiation from ICU admission. Conclusions: Mortality in children requiring continuous renal replacement therapy remains high and seems to be related to the underlying disease, the severity of illness, and the degree of fluid overload. In critically ill children at high risk for developing acute kidney injury and fluid overload, earlier initiation of continuous renal replacement therapy might result in decreased mortality.

BACKGROUND Age-specific reference intervals (RIs) have been developed for biochemistry analytes in children. However, the ability to interpret results from multiple laboratories for 1 individual is limited. This study reports a head-to-head comparison of reference values and age-specific RIs for 30 biochemistry analytes for children across 5 analyzer types. METHODS Blood was collected from healthy newborns and children 30 days to &lt;18 years of age. Serum aliquots from the same individual were analyzed on 5 analyzer types. Differences in the mean reference values of the analytes by the analyzer types were investigated using mixed-effect regression analysis and by comparing maximum variation between analyzers with analyte-specific allowable total error reported in the Westgard QC database. Quantile regression was used to estimate age-specific RIs using power variables in age selected by fractional polynomial regression for the mean, with modification by sex when appropriate. RESULTS The variations of age-specific mean reference values between analyzer types were within allowable total error (Westgard QC) for most analytes, and common age-specific reference limits were reported as functions of age and/or sex. Analyzer-specific reference limits for all analytes on 5 analyzer types are also reported as functions of age and/or sex. CONCLUSIONS This study provides quantitative and qualitative measures of the extent to which results for individual children can or cannot be compared across analyzer types, and the feasibility of RI harmonization. The reported equations enable incorporation of age-specific RIs into laboratory information systems for improving evidence-based clinical decisions in children.

BACKGROUND: Recent referrals of transgender young people to specialist gender services worldwide have risen exponentially, resulting in wait times of 1-2 years. To manage this demand, we introduced an innovative First Assessment Single-Session Triage (FASST) clinic that provides information and support to young people and their families and triages them onto a secondary waitlist for subsequent multidisciplinary care. Although FASST has been shown to substantially reduce initial wait times, its clinical impact is unknown.METHODS: FASST was evaluated by analysis of clinical surveys and qualitative interviews. A total of 142 patients were surveyed before and after FASST, and comparison was made to a historical control group of 120 patients who did not receive FASST. In-depth interviews were also held with FASST attendees (n 5 14) to explore experiences of FASST, and inductive content analysis was performed.RESULTS: After FASST, there were improvements in depression (standardized mean difference [SMD] 5 À0.24; 95% confidence interval [CI]: À0.36 to À0.11; P < .001), anxiety (SMD 5 À0.14; 95% CI: À0.26 to À0.02; P 5 .025) and quality of life (SMD 5 .39; 95% CI: 0.23 to 0.56; P < .001). Compared with historical controls, those attending FASST showed reduced depression (SMD 5 À0.24; 95% CI: À0.50 to 0.01; P 5 .065) and anxiety (SMD 5 À0.31; 95% CI: À0.57 to À0.05; P 5 .021). FASST attendees qualitatively described an increased sense of agency, which was related to improved outlook, validation, sense of self, and confidence.CONCLUSIONS: Given burgeoning waitlists of pediatric gender services worldwide, this study suggests FASST may prove a useful model of care elsewhere.

Background Globally, the majority of newborns requiring resuscitation at birth are full term or late-preterm infants. These infants typically have their umbilical cord clamped early (ECC) before moving to a resuscitation platform, losing the potential support of the placental circulation. Physiologically based cord clamping (PBCC) is clamping the umbilical cord after establishing lung aeration and holds promise as a readily available means of improving early newborn outcomes. In mechanically ventilated lambs, PBCC improved cardiovascular stability and reduced hypoxia. We hypothesised that PBCC compared to ECC would result in higher heart rate (HR) in infants needing resuscitation, without compromising safety. Methods and findings Between 4 July 2018 and 18 May 2021, infants born at ≥32+0 weeks’ gestation with a paediatrician called to attend were enrolled in a parallel-arm randomised trial at 2 Australian perinatal centres. Following initial stimulation, infants requiring further resuscitation were randomised within 60 seconds of birth using a smartphone-accessible web link. The intervention (PBCC) was to establish lung aeration, either via positive pressure ventilation (PPV) or effective spontaneous breathing, prior to cord clamping. The comparator was early cord clamping (ECC) prior to resuscitation. The primary outcome was mean HR between 60 to 120 seconds after birth, measured using 3-lead electrocardiogram, extracted from video recordings blinded to group allocation. Nonrandomised infants had deferred cord clamping (DCC) ≥120 seconds in the observational study arm. Among 508 at-risk infants enrolled, 123 were randomised (n = 63 to PBCC, n = 60 to ECC). Median (interquartile range, IQR) for gestational age was 39.9 (38.3 to 40.7) weeks in PBCC infants and 39.6 (38.4 to 40.4) weeks in ECC infants. Approximately 49% and 50% of the PBCC and ECC infants were female, respectively. Five infants (PBCC = 2, ECC = 3, 4% total) had missing primary outcome data. Cord clamping occurred at a median (IQR) of 136 (126 to 150) seconds in the PBCC arm and 37 (27 to 51) seconds in the ECC arm. Mean HR between 60 to 120 seconds after birth was 154 bpm (beats per minute) for PBCC versus 158 bpm for ECC (adjusted mean difference −6 bpm, 95% confidence interval (CI) −17 to 5 bpm, P = 0.39). Among 31 secondary outcomes, postpartum haemorrhage ≥500 ml occurred in 34% and 32% of mothers in the PBCC and ECC arms, respectively. Two hundred ninety-five nonrandomised infants (55% female) with median (IQR) gestational age of 39.6 (38.6 to 40.6) weeks received DCC. Data from these infants was used to create percentile charts of expected HR and oxygen saturation in vigorous infants receiving DCC. The trial was limited by the small number of infants requiring prolonged or advanced resuscitation. PBCC may provide other important benefits we did not measure, including improved maternal–infant bonding and higher iron stores. Conclusions In this study, we observed that PBCC resulted in similar mean HR compared to infants receiving ECC. The findings suggest that for infants ≥32+0 weeks’ gestation who receive brief, effective resuscitation at closely monitored births, PBCC does not provide additional benefit over ECC (performed after initial drying and stimulation) in terms of key physiological markers of transition. PBCC was feasible using a simple, low-cost strategy at both cesarean and vaginal births. The percentile charts of HR and oxygen saturation may guide clinicians monitoring the transition of at-risk infants who receive DCC. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12618000621213.

IntroductionThe clinical interpretation of laboratory tests is reliant on reference intervals. However, the accuracy of a reference interval is dependent on the selected reference population, and in paediatrics, the ability of the reference interval to reflect changes associated with growth and age, as well as sex and ethnicity. Differences in reagent formulations, methodologies and analysers can also impact on a reference interval. To date, no direct comparison of reference intervals for common analytes using different analysers in children has been published. The Harmonising Age Pathology Parameters in Kids (HAPPI Kids) study aims to establish age-appropriate reference intervals for commonly used analytes in the routine clinical care of neonates and children, and to determine the feasibility of paediatric reference interval harmonisation by comparing age-appropriate reference intervals in different analysers for multiple analytes.Methods and analysisThe HAPPI Kids study is a prospective cross-sectional study, collecting paediatric blood samples for analysis of commonly requested biochemical, immunological and haematological tests. Venous blood samples are collected from healthy premature neonates (32–36 weeks of gestation), term neonates (from birth to a maximum of 72 hours postbirth) and children aged 30 days to ≤18 years (undergoing minor day surgical procedures). Blood samples are processed according to standard laboratory procedures and, if not processed immediately, stored at –80°C. A minimum of 20 samples is analysed for every analyte for neonates and then each year of age until 18 years. Analytical testing is performed according to the standard operating procedures used for clinical samples. Where possible, sample aliquots from the same patients are analysed for an analyte across multiple commercially available analysers.Ethics and disseminationThe study protocol was approved by The Royal Children’s Hospital, Melbourne, Ethics in Human Research Committee (34183 A). The study findings will be published in peer-reviewed journals and shared with clinicians, laboratory scientists and laboratories.

Despite high support for vaccines, nearly half of Australian parents have some concerns and a quarter lack vaccine decision-making confidence regarding childhood vaccines. Parents frequently access and report high trust in HCPs, who are best placed to address parental vaccine concerns through provision of clear information, using effective communication strategies. Further research in more highly hesitant populations is required to determine the relationship between the level and nature of vaccination concerns and vaccine uptake.