Respiratory function monitoring during early resuscitation and prediction of outcomes in prematurely born infants.

OBJECTIVES: Over the last decade, there has been increased use of end-tidal carbon dioxide (ETCO2) and oxygen saturation (SpO2) monitoring during resuscitation of prematurely born infants in the delivery suite. Our objectives were to test the hypotheses that low end-tidal carbon dioxide (ETCO2) levels, low oxygen saturations (SpO2) and high expiratory tidal volumes (VTE) during the early stages of resuscitation would be associated with adverse outcomes in preterm infants. METHODS: Respiratory recordings made in the first 10 min of resuscitation in the delivery suite of 60 infants, median GA 27 (interquartile range 25-29) weeks were analysed. The results were compared of infants who did or did not die or did or did not develop intracerebral haemorrhage (ICH) or bronchopulmonary dysplasia (BPD). RESULTS: Twenty-five infants (42%) developed an ICH and 23 (47%) BPD; 11 (18%) died. ETCO2 at approximately 5 min after birth was lower in infants who developed an ICH, this remained significant after adjusting for gestational age, coagulopathy and chorioamnionitis (p=0.03). ETCO2 levels were lower in infants who developed ICH or died compared to those that survived without ICH, which remained significant after adjustment for gestational age, Apgar score at 10 min, chorioamnionitis and coagulopathy (p=0.004). SpO2 at approximately 5 min was lower in the infants who died compared to those who survived which remained significant after adjusting for the 5-min Apgar score and chorioamnionitis (p=0.021). CONCLUSIONS: ETCO2 and SpO2 levels during early resuscitation in the delivery suite were associated with adverse outcomes.

Airwave oscillometry and spirometry in children with asthma or wheeze.

OBJECTIVE: Lung function testing is used in diagnosing asthma and assessing asthma control. Spirometry is most commonly used, but younger children can find performing this test challenging. Non-volitional tests such as airwave oscillometry (AOS) may be helpful in that population. We compared the success of spirometry and AOS in assessing bronchodilator responsiveness in children. METHODS: AOS was conducted alongside routine lung function testing. Resistance at 5 Hz (R5), the difference between the resistance at 5 and 20 Hz (R5-20) and the area under the reactance curve (AX) were assessed. Patients between 5 and 16 years old attending clinic with wheeze or asthma were assessed. Patients performed AOS, followed by spirometry and were then given 400 µg salbutamol; the tests were repeated 15 minutes later. RESULTS: Lung function testing was performed in 47 children of whom 46 (98%) and 32 (68%) performed acceptable baseline oscillometry and spirometry, respectively (p < 0.001). Children unable to perform acceptable spirometry were younger (7.35, range: 5.4-10.3 years) than those who could (10.4, range: 5.5-16.9 years), p < 0.001. The baseline z-scores of AOS R5 correlated with FEV1 (r = 0.499, p = 0.004), FEF75 (r = 0.617, p < 0.001), and FEV1/FVC (r = 0.618, p < 0.001). There was a positive bronchodilator response assessed by spirometry (change in FEV1 ≥ 12%) in eight children which corresponded to a change in R5 of 36% (range: 30%-50%) and a change in X5 of 39% (range: 15%-54%). CONCLUSIONS: Oscillometry is a useful adjunct to spirometry in assessing young asthmatic children's lung function. The degree of airway obstruction, however, might affect the comparability of the results of the two techniques.

Use of impulse oscillometry to assess lung function in prematurely born children and young people: Comparisons with spirometry.

Premature birth is a risk factor for bronchopulmonary dysplasia (BPD); both of which are associated with obstructive airway disease throughout childhood. Impulse oscillometry (IOS) is an effort-independent, passive measure of tidal breathing, which could have benefits in assessing lung function amongst younger patients unable to perform valid spirometry. A literature search was conducted to investigate the use of IOS in prematurely born children and young people. IOS results correlate with those of spirometry. Reversibility of airway obstruction in children with BPD is variable. IOS could have benefits in assessing individual patient response and suitability for bronchodilator therapy. More work, however, is required to establish multi-ethnic reference ranges and standardise commercially available devices prior to its routine incorporation into clinical practice.

Pseudorandom Noise Forced Oscillation Technique to Assess Lung Function in Prematurely Born Children.

The forced oscillation technique (FOT) is a non-volitional assessment that is used during tidal breathing. A variant of FOT uses a pseudorandom noise (PRN) signal which we postulated might have utility in assessing lung function in prematurely born children. We, therefore, undertook a systematic review to evaluate the evidence regarding PRN FOT. A comprehensive search of the literature was conducted by using the following databases: Medline, Embase, Web of Science and CINAHL. Observational studies, case series/reports and randomized-controlled trials were eligible for inclusion. Article abstracts and full texts were screened independently by two reviewers, with disagreements resolved by discussion or a third reviewer if necessary. Five studies were included (n = 587 preterm children). Three compared PRN FOT with spirometry, and two compare it to the interrupter technique. Most studies failed to report comprehensive methodology of the frequency spectra used to generate the PRN signal. There was evidence that poorer lung function, as assessed by PRN FOT, was associated with a greater burden of respiratory symptoms, but there was insufficient evidence to determine whether PRN FOT performed better than other lung-function tests. Detailed methodological documentation, in accordance with ERS guidance, is needed to assess the benefits of PRN FOT prior to routine clinical incorporation to assess prematurely born children.

Postnatal diuretics, weight gain and home oxygen requirement in extremely preterm infants.

OBJECTIVES: Diuretics are often given to infants with evolving/established bronchopulmonary dysplasia (BPD) with the hope of improving their pulmonary outcomes. We aimed to determine if diuretic use in preterm infants was associated with improved pulmonary outcomes, but poorer weight gain. METHODS: An observational study over a 5 year period was undertaken of all infants born at less than 29 weeks of gestation and alive at discharge in all neonatal units in England who received consecutive diuretic use for at least 7 days. Postnatal weight gain and home supplementary oxygen requirement were the outcomes. A literature review of randomised controlled trials (RCTs) and crossover studies was undertaken to determine if diuretic usage was associated with changes in lung mechanics and oxygenation, duration of supplementary oxygen and requirement for home supplementary oxygen. RESULTS: In the observational study, 9,457 infants survived to discharge, 44.6% received diuretics for at least 7 days. Diuretic use was associated with an increased probability of supplementary home oxygen of 0.14 and an increase in weight gain of 2.5 g/week. In the review, seven of the 10 studies reported improvements only in short term lung mechanics. There was conflicting evidence regarding whether diuretics resulted in short term improvements in oxygenation. CONCLUSIONS: Diuretic use was not associated with a reduction in requirement for supplemental oxygen on discharge. The literature review highlighted a lack of RCTs assessing meaningful long-term clinical outcomes. Randomised trials are needed to determine the long-term risk benefit ratio of chronic diuretic use.

An OxPLORE Initiative Evaluating Children's Surgery Resources Worldwide: A Cross-sectional Implementation of the OReCS Document.

BACKGROUND: The Global Initiative for Children's Surgery (GICS) group produced the Optimal Resources for Children's Surgery (OReCS) document in 2019, listing standards of children's surgical care by level of healthcare facilities within low resource settings. We have previously created and piloted an audit tool based on the OReCS criteria in a high-income setting. In this study, we aimed to validate its use in identifying gaps in children's surgery provision worldwide. METHODS: Our OReCS audit tool was implemented in 10 hospitals providing children's surgery across eight countries. Collaborators were recruited via the Oxford Paediatrics Linking Our Research with Electives (OxPLORE) international network of medical students and trainees. The audit tool measured a hospital's current capacity for children's surgery. Data were analysed firstly to express the percentage of 'essential' criteria met for each specialty. Secondly, the 'OxPLORE method' was used to allocate each hospital specialty a level based on procedures performed and resources available. A User Evaluation Tool (UET) was developed to obtain feedback on the ease of use of the tool. RESULTS: The percentage of essential criteria met within each category varied widely between hospitals. The level given to hospitals for subspecialties based on OReCS criteria often did not reflect their self-defined level. The UET indicated the audit tool was practicable across multiple settings. CONCLUSIONS: We recommend the use of the OReCS criteria to identify areas for local hospital improvement and inform national children's surgical plans. We have made informed suggestions to increase usability of the OReCS audit tool.

Is microwave ablation an alternative to stereotactic ablative body radiotherapy in patients with inoperable early-stage primary lung cancer?

A best evidence topic was written according to a structured protocol. The question addressed was: in patients with inoperable early-stage primary lung cancer does microwave ablation (MWA) or stereotactic ablative body radiotherapy (SBRT) achieve improved outcomes in terms of local control, recurrence, survival and complications? Altogether, more than 550 papers were found using the reported search, of which 12 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. No single study directly compared the effects of MWA with SBRT. However, the best available evidence for MWA (7 studies) was compared to that for SBRT (5 studies). The range of 3-year survival reported for MWA was 29.2-84.7%, compared with 42.7-63.5% for SBRT. The range of median survival was 35-60 months for MWA and 32.6-48 months for SBRT. This suggests similar outcomes between these two 2 techniques. Different side-effect profiles were observed between techniques with MWA associated with pneumothorax and fever and SBRT most commonly causing radiation pneumonitis and rib fractures. The evidence base for MWA is less than that for SBRT and is heterogenous in terms of participants and technical design. However, within these limitations, we conclude that MWA appears comparable with SBRT in terms of local control and survival rates.

Cross-reactive dengue virus-derived monoclonal antibodies to Zika virus envelope protein: Panacea or Pandora's box?

BACKGROUND: Dengue Virus (DENV) and Zika Virus (ZIKV) are closely related flaviviruses, circulating in overlapping geographical regions. The recent ZIKV epidemic has been linked to an explosion in reports of microcephaly and neurological defects. It is conceivable that our knowledge of DENV might potentiate the development of a ZIKV vaccine due to the close phylogenetic relationship between these flaviviruses and cross-reactive antibodies, principally to the envelope protein (E protein). Alternatively, cross-reactive antibodies that are generated following vaccination or infection, might become damaging during subsequent infections. MAIN BODY: The aims of this review are to collate and analyse data from a recent series of DENV-derived monoclonal antibody (mAb) panels from different research groups. These panels measured DENV-mAb activity against ZIKV in terms of antibody-dependent enhancement (ADE) and neutralisation. Methodology used across groups was compared and critiqued. Furthermore, the specific antibody targets on E protein were considered and their therapeutic potential evaluated. Shortcomings of hmAb panels suggest ADE may be over-estimated and neutralisation underestimated, as compared to clinical situations. It remains unknown whether preference of enhancement or neutralisation by antibodies to ZIKV E protein is dictated by quantitative aspects of antibody titre or epitope specific variation. Additionally, little is known about how duration between flavivirus reinfections affect secondary antibody response. CONCLUSION: This review concludes that our current knowledge of cross-reactive antibodies to E protein is inadequate to anticipate the outcome of deploying an E protein based vaccine to regions co-infected by DENV and ZIKV.