Less-Invasive Surfactant Administration for Neonatal Respiratory Distress Syndrome: A Consensus Guideline.

INTRODUCTION: Less-invasive surfactant administration (LISA) is a method of surfactant delivery to preterm infants for treating respiratory distress syndrome (RDS), which can reduce the composite risk of death or bronchopulmonary dysplasia and the time on mechanical ventilation. METHODS: A systematic literature search of studies published up to April 2021 on minimally invasive catheter surfactant delivery in preterm infants with RDS was conducted. Based on these studies, with parental feedback sought via an online questionnaire, 9 UK-based specialists in neonatal respiratory disease developed their consensus for implementing LISA. Recommendations were developed following a modified, iterative Delphi process using a questionnaire employing a 9-point Likert scale and an a priori level of agreement/disagreement. RESULTS: Successful implementation of LISA can be achieved by training the multidisciplinary team and following locally agreed guidance. From the time of the decision to administer surfactant, LISA should take <30 min. The comfort of the baby and requirements to maintain non-invasive respiratory support are important. While many infants can be managed without requiring additional sedation/analgesia, fentanyl along with atropine may be considered. Parents should be provided with sufficient information about medication side effects and involved in treatment discussions. CONCLUSION: LISA has the potential to improve outcomes for preterm infants with RDS and can be introduced as a safe and effective part of UK-based neonatal care with appropriate training.

Stabilisation of the preterm infant in the delivery room using nasal high flow: A 5-year retrospective analysis.

AIM: This study reviews clinical outcomes after initiating a routine policy of preterm respiratory stabilisation using nasal high flow (HF) in the delivery room (DR). METHOD: This was a retrospective observational cohort study in a single-centre neonatal intensive care unit and included all neonates born before 32 weeks of gestation between 1 April 2015 and 31 March 2020. Stabilisation measures and outcomes were recorded including oxygen requirements, admission temperature, surfactant administration, invasive ventilation within 72 h of birth, bronchopulmonary dysplasia (BPD) and death. RESULTS: There were 491 eligible babies during the 5-year epoch. 292 were stabilised using HF in the DR. The median admission temperature in babies transferred on HF was 36.8°C, and the median FiO2 at admission was 25%. 45% of these infants received surfactant. At 72 postnatal hours, 78% were either sustained on HF or were either self-ventilating in air (SVIA) or receiving low-flow nasal cannula (LFNC) respiratory support. 27% were intubated within 7 days. At 36 weeks postmenstrual age, 36% of survivors had BPD. CONCLUSION: We have demonstrated that preterm babies <32 weeks can be effectively stabilised on HF in the DR.

Survey of less Invasive Surfactant Administration in England, slow adoption and variable practice.

AIM: National survey to evaluate the uptake of Less Invasive Surfactant Administration (LISA) in neonatal units across England. METHODS: A web-based survey was sent out by email to all 150 neonatal units in England. It consisted of questions regarding indications for LISA, the practicalities of the procedure and reasons for not using this technique. RESULTS: The response rate was 96% (144/150 units). Only 11% of units are using LISA, but majority (78%) would consider implementing LISA on their unit. 56% would also consider LISA on delivery suite. Challenges identified are having a guideline and staff training. 61% of units have set the target population ≥27 weeks. On sub-analysis, for tertiary units, the trend for LISA is ≥26 weeks. The median FiO2 threshold for LISA is 0.3 (IQR 0.3-0.4) in less than 28 weeks gestational age (GA), and 0.4 in higher gestations. The most common suggestion for premedication is fentanyl (32%). CONCLUSION: The uptake of LISA in England is low comparing to the rest of Europe. Even though many units are considering implementing LISA, there is lack of training and national guidelines. There is urgent need for standardisation of practice and clear indications for LISA.

Use of Intraosseous Needles in Neonates: A Systematic Review.

BACKGROUND: The use of intraosseous (IO) access during resuscitation is widely accepted and promoted in paediatric medicine but features less prominently in neonatal training. Whilst umbilical venous catheterization (UVC) is a reliable method of delivering emergency drugs and fluids, it is not always achievable in a timely manner. IO access warrants exploration as an alternative. AIM: Conduct a systematic review of existing literature to examine the evidence for efficacy and safety of IO devices in neonatal patients, from birth to discharge. METHOD: A search of PubMed, Ovid, Medline, and Embase was carried out. Abstracts were screened for relevance to focus on neonatal-specific literature and studies which carried out separate analyses for neonates (infants <28 days of age or resident on a neonatal unit). RESULTS: One case series and 12 case reports describe IO device insertion into 41 neonates, delivering a variety of drugs, including adrenaline (epinephrine) and volume resuscitation. Complications range from none to severe. Cadaveric studies show that despite a small margin for error, IO devices can be correctly sited in neonates. Simulation studies suggest that IO devices may be faster and easier to site than UVC, even in experienced hands. CONCLUSION: IO access should be available on neonatal units and considered for early use in neonates where other access routes have failed. Appropriate training should be available to staff in addition to existing life support and UVC training. Further studies are required to assess the optimal device, position, and whether medication can be delivered IO as effectively as by UVC. If IO devices provide a faster method of delivering adrenaline effectively than UVC, this may lead to changes in neonatal resuscitation practice.

Nasal High-Flow Therapy as Primary Respiratory Support for Preterm Infants without the Need for Rescue with Nasal Continuous Positive Airway Pressure.

AIM: To evaluate the effectiveness of nasal high-flow therapy (nHFT) as primary respiratory support for preterm infants with respiratory distress syndrome (RDS) in two tertiary neonatal units. METHODS: A retrospective outcome analysis of initial respiratory support strategies was performed in two tertiary neonatal units in the UK: John Radcliffe Hospital (JRH), Oxford and St Peter's Hospital (SPH), Chertsey. Infants born between 28+0 and 36+6 weeks gestational age (GA) between May 2013 and June 2015 were included. RESULTS: A total of 381 infants, 191 from JRH and 190 from SPH, were analysed. Infants were stabilised in the delivery room using mask continuous positive airway pressure followed by nHFT. Endotracheal intubation was performed according to local protocols, depending on the severity of RDS. There were significant differences in initial intubation rates according to GA (26% JRH vs. 16.9% SPH, p < 0.001 for babies < 32 weeks GA, and 8.2% JRH vs. 6.5% SPH, p < 0.001 for babies > 32 weeks GA); however, most infants were successfully transitioned to nHFT. Intubation rates during the first 72 h were comparable between centres (14.7% JRH vs. 11.1% SPH, p = 0.29). There were no differences in neonatal morbidities, including air leak, duration of oxygen supplementation, bronchopulmonary dysplasia, sepsis, retinopathy of prematurity, intraventricular haemorrhage, necrotising enterocolitis, or median time to full-suck feeds. CONCLUSION: Use of nHFT for primary respiratory support, without use of nasal continuous positive airway pressure as "rescue" treatment, resulted in intubation rates lower or comparable to published data from randomised controlled trials.

Randomised cross-over study of automated oxygen control for preterm infants receiving nasal high flow.

OBJECTIVE: To evaluate a prototype automated controller (IntellO2) of the inspired fraction of oxygen (FiO2) in maintaining a target range of oxygen saturation (SpO2) in preterm babies receiving nasal high flow (HF) via the Vapotherm Precision Flow. DESIGN: Prospective two-centre order-randomised cross-over study. SETTING: Neonatal intensive care units. PATIENTS: Preterm infants receiving HF with FiO2 ≥25%. INTERVENTION: Automated versus manual control of FiO2 to maintain a target SpO2 range of 90%-95% (or 90%-100% if FiO2=21%). MAIN OUTCOME MEASURES: The primary outcome measure was per cent of time spent within target SpO2 range. Secondary outcomes included the overall proportion and durations of SpO2 within specified hyperoxic and hypoxic ranges and the number of in-range episodes per hour. RESULTS: Data were analysed from 30 preterm infants with median (IQR) gestation at birth of 26 (24-27) weeks, study age of 29 (18-53) days and study weight 1080 (959-1443) g. The target SpO2 range was achieved 80% of the time on automated (IntellO2) control (IQR 70%-87%) compared with 49% under manual control (IQR 40%-57%; p<0.0001). There were fewer episodes of SpO2 below 80% lasting at least 60 s under automated control (0 (IQR 0-1.25)) compared with manual control (5 (IQR 2.75-14)). There were no differences in the number of episodes per hour of SpO2 above 98% (4.5 (IQR 1.8-8.5) vs 5.5 (IQR 1.9-14); p=0.572) between the study arms. CONCLUSIONS: The IntellO2 automated oxygen controller maintained patients in the target SpO2 range significantly better than manual adjustments in preterm babies receiving HF. TRIAL REGISTRATION NUMBER: NCT02074774.

rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial.

OBJECTIVE: To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants. STUDY DESIGN: This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 230/7 weeks to 276/7 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 µg/kg/ 24 hours, continuous intravenous infusion from <24 hours of birth to postmenstrual age 296/7 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 404/7 weeks. Target exposure was ≥70% IGF-1 measurements within 28-109 µg/L and ≥70% intended therapy duration. The primary endpoint was maximum severity of ROP. Secondary endpoints included time to discharge from neonatal care, bronchopulmonary dysplasia, intraventricular hemorrhage, and growth measures. RESULTS: Overall, 61 infants were allocated to rhIGF-1/rhIGFBP-3, 60 to standard care (full analysis set); 24 of 61 treated infants achieved target exposure (evaluable set). rhIGF-1/rhIGFBP-3 did not decrease ROP severity or ROP occurrence. There was, however, a 53% decrease in severe bronchopulmonary dysplasia in the full analysis set (21.3% treated vs 44.9% standard care), and an 89% decrease in the evaluable set (4.8% vs 44.9%; P = .04 and P = .02, respectively) for severity distribution between groups. There was also a nonsignificant trend toward decrease in grades 3-4 intraventricular hemorrhage in the full analysis set (13.1% vs 23.3%) and in the evaluable set (8.3% vs 23.3%). Fatal serious adverse events were reported in 19.7% of treated infants (12/61) and 11.7% of control infants (7/60). No effect was observed on time to discharge from neonatal care/growth measures. CONCLUSIONS: rhIGF-1/rhIGFBP-3 did not affect development of ROP, but decreased the occurrence of severe bronchopulmonary dysplasia, with a nonsignificant decrease in grades 3-4 intraventricular hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01096784.

Decisionmaking in practice: The dynamics of muddling through.

An alternative to conventional models that treat decisions as open-loop independent choices is presented. The alterative model is based on observations of work situations such as healthcare, where decisionmaking is more typically a closed-loop, dynamic, problem-solving process. The article suggests five important distinctions between the processes assumed by conventional models and the reality of decisionmaking in practice. It is suggested that the logic of abduction in the form of an adaptive, muddling through process is more consistent with the realities of practice in domains such as healthcare. The practical implication is that the design goal should not be to improve consistency with normative models of rationality, but to tune the representations guiding the muddling process to increase functional perspicacity.

Neonatal listeriosis in the UK 2004-2014.

OBJECTIVE: To define the clinical features and outcomes of neonatal listeriosis, and identify the maternal risk factors to seek scope for improvement. METHODS: Neonatal listeriosis was identified prospectively from a United Kingdom neonatal infection surveillance network (neonIN) between 2004 and 2014. The participating neonatal units completed a study-specific proforma. RESULTS: The incidence of neonatal listeriosis was 3.4 per 100,000 live births. Of the 21 cases identified, 19 were confirmed with a median gestational age of 33 weeks and a median birth weight of 1960 g. The majority had clinical features (95%, 18/19), presented within the first 24 h (95%, 18/19), and received penicillin empirically (94%, 18/19). The neonatal case-fatality rate was 21% (24% if probable cases were included). A proportion of mothers were investigated (60%, 12/18) and diagnosed with listeriosis (58%, 7/12); 32% (6/19) were treated with antibiotics but only 33% (6/12) included penicillin. DISCUSSION: Despite its rarity and the prompt and appropriate use of antibiotics neonatal listeriosis has a high case-fatality rate. There is room for improvement in the adherence to the empiric antibiotic choice for puerperal sepsis, according to the national guidelines as this, would target listeriosis. Strategies should be in place to prevent pregnancy-associated listeriosis in higher risk population.

Stabilisation of premature infants in the delivery room with nasal high flow.

OBJECTIVE: This was a pilot study to determine the feasibility of using nasal high flow (nHF) (also known as heated humidified high-flow nasal cannula) for stabilisation of babies born at <30 weeks gestation in the delivery room (DR) and transfer to the neonatal intensive care unit (NICU). DESIGN: Observational study. SETTING: Single-centre NICU. PATIENTS: Infants born at <30 weeks gestation. INTERVENTIONS: Stabilisation and transfer to NICU using nHF. MAIN OUTCOME MEASURES: Feasibility of stabilisation as defined by successful transfer and clinical measures of stability at admission to NICU including oxygen requirement, temperature, requirement for surfactant and inotrope use within 72 h of delivery. RESULTS: Twenty-eight babies were enrolled after written parental consent had been obtained. 25/28 were successfully stabilised in the DR and transferred to the NICU on nHF. The average admission temperature for babies transferred on nHF was 36.9°C and the average inspired oxygen at admission was 29%. Less than half (48%) required surfactant and 60% were still on nHF 72 h after admission. 1 baby received inotropes. CONCLUSIONS: Our study suggests that using nHF for stabilisation of premature infants in the DR and subsequent transfer to NICU is feasible. CLINICAL TRIAL REGISTRATION NUMBER: NCT01991886.

Supporting 'Baby Friendly': a quality improvement initiative for the management of transitional neonatal hypoglycaemia.

We describe a quality improvement initiative conducted in a medium-sized district general hospital with a neonatal intensive care unit, which involved working with the multidisciplinary team to create a 'Baby Friendly' neonatal hypoglycaemia pathway with implementation of dextrose gel as a first-line treatment. As a result of the project, formula supplementation rates and admissions for transitional hypoglycaemia were reduced and breastfeeding rates at 3 months improved. This initiative demonstrates that evidence-based guidelines with multidisciplinary team input can improve standards of care.

Encouraging formative assessments of leadership for foundation doctors.

BACKGROUND: Clinical leadership is considered essential for maintaining and improving patient care and safety in the UK, and is incorporated in the curriculum for all trainee doctors. CONTEXT: Despite the growing focus on the importance of leadership, and the introduction of the Medical Leadership Competency Framework (MLCF) in the UK, leadership education for doctors in training is still in its infancy. Assessment is focused on clinical skills, and trainee doctors receive very little formal feedback on their leadership competencies. INNOVATION: In this article we describe the approach taken by Health Education Kent, Sussex and Surrey (HEKSS) to raise the profile of leadership amongst doctors in training in the South Thames Foundation School (STFS). An annual structured formative assessment in leadership for each trainee has been introduced, supported by leadership education for both trainees and their supervisors in HEKSS trusts. We analysed over 500 of these assessments from the academic year 2012/13 for foundation doctors in HEKSS trusts, in order to assess the quality of the feedback. From the analysis, potential indicators of more effective formative assessments were identified. These may be helpful in improving the leadership education programme for future years. IMPLICATIONS: There is a wealth of evidence to highlight the importance and value of formative assessments; however, particularly for foundation doctors, these have typically been focused on assessing clinical capabilities. This HEKSS initiative encourages doctors to recognise leadership opportunities at the beginning of their careers, seeks to help them understand the importance of acquiring leadership skills and provides structured feedback to help them improve. Leadership education for doctors in training is still in its infancy.

Generalized variational principle for excited states using nodes of trial functions.

The familiar variational principle provides an upper bound to the ground-state energy of a given Hamiltonian. This allows one to optimize a trial wave function by minimizing the expectation value of the energy. This approach is also trivially generalized to excited states, so that given a trial wave function of a certain symmetry, one can compute an upper bound to the lowest-energy level of that symmetry. In order to generalize further and build an upper bound of an arbitrary excited state of the desired symmetry, a linear combination of basis functions is generally used to generate an orthogonal set of trial functions, all bounding their respective states. However, sometimes a compact wave-function form is sought, and a basis-set expansion is not desirable or possible. Here we present an alternative generalization of the variational principle to excited states that does not require explicit orthogonalization to lower-energy states. It is valid for one-dimensional systems and, with additional information, to at least some n-dimensional systems. This generalized variational principle exploits information about the nodal structure of the trial wave function, giving an upper bound to the exact energy without the need to build a linear combination of basis functions. To illustrate the theorem we apply it to a nontrivial example: the 1s2s (1)S excited state of the helium atom.

Management dilemma in a paediatric patient with chronic gastric volvulus: a case report.

Gastric volvulus in children is rare. While the acute form is a surgical emergency, the chronic form may be managed either surgically or conservatively. The present report describes a premature (26+1 weeks) Afro-Caribbean neonate girl who presented with severe multiple bradycardias and apnoeas; she subsequently underwent pH monitoring and a barium study which demonstrated gastro-oesophageal reflux disease (GORD) and gastric volvulus. The patient represented a management dilemma as there were delays in establishing the diagnosis since medical treatment was started before pH monitoring was performed, and because of complications of prematurity precluding surgical treatment. This case supports an association between GORD and gastric volvulus while arguing that the mode of treatment should be based upon the severity of symptoms. This case is of particular interest to paediatricians who might consider this diagnosis in infants presenting with non-specific gastrointestinal and feeding problems particularly in association with GORD.

The influence of gestational stage on urinary iodine excretion in pregnancy.

INTRODUCTION: Median urinary iodine concentration (UIC) is the most commonly used indicator of population iodine nutrition. However, its validity as an indicator of dietary intake relies on a stable relationship between dietary iodine intake and urinary excretion. Physiological alterations in normal pregnancy, such as increased glomerular filtration rate, potentially invalidate UIC as an assessment tool in pregnancy. OBJECTIVE: The objective of the study was to document the impact of advancing gestation on UIC in normal pregnancy and determine whether the current reference intervals for general population iodine monitoring are appropriate for use in the context of pregnancy. DESIGN: Tasmania has a well-described history of mild iodine deficiency (school-age median UIC of 84 microg/liter). We assessed UIC in 759 urine samples from 431 women attending the Antenatal Clinic at the Royal Hobart Hospital, Tasmania's primary teaching hospital. MAIN OUTCOME: The overall median UIC during pregnancy was 75 microg/liter (95% confidence interval 70.03-79.97 microg/liter) at a median gestation of 19.4 wk. Stratification by gestation, however, revealed a dynamic relationship between ioduria and gestation. Median UIC was elevated in early pregnancy and subsequently declined with advancing gestation. CONCLUSION: In this mildly iodine-deficient population, current reference intervals for UIC overestimated the adequacy of iodine nutrition during the first and early second trimester of pregnancy. Gestation-specific UIC reference intervals are required to classify iodine nutrition during pregnancy. This is particularly important in populations with borderline iodine deficiency.

Colorectal cancer: a summary of the evidence for screening and prevention.

Colorectal cancer causes significant morbidity and mortality in the United States. The incidence of colorectal cancer can be reduced with increasing efforts directed at mass screening of average-risk adults 50 years and older. Currently, fecal occult blood test and flexible sigmoidoscopy have the highest levels of evidence to support their use for colorectal cancer screening. Colonoscopy does not have a proven colorectal cancer mortality benefit, but it does have the greatest single-test accuracy, and it is the final test in the pathway to evaluate and treat patients with other abnormal screening tests. Double-contrast barium enema has sparse data of effectiveness. Computed tomographic colonography, fecal DNA testing, and Pillcam Colon are promising tests that need further study before they can be recommended for widespread screening. Routine screening should continue until 75 years of age. There is good evidence that fiber and antioxidants are not effective for primary prevention of colorectal cancer; they should not be recommended for chemoprevention. There is good evidence that aspirin, nonsteroidal antiinflammatory drugs, and cyclooxygenase-2 inhibitors are effective for decreasing the risk of colorectal cancer and adenomatous polyps, but increased risks, such as gastrointestinal bleeding, limit their usefulness. There is fair evidence that obesity is associated with colorectal cancer. Additional studies are needed on decreased fat intake and red meat consumption, and the use of calcium, vitamin D, and statins before these can be recommended for primary prevention of colorectal cancer.