Success of blinding a procedural intervention in a randomised controlled trial in preterm infants receiving respiratory support.

BACKGROUND: Blinding of treatment allocation from treating clinicians in neonatal randomised controlled trials can minimise performance bias, but its effectiveness is rarely assessed. METHODS: To examine the effectiveness of blinding a procedural intervention from treating clinicians in a multicentre randomised controlled trial of minimally invasive surfactant therapy versus sham treatment in preterm infants of gestation 25-28 weeks with respiratory distress syndrome. The intervention (minimally invasive surfactant therapy or sham) was performed behind a screen within the first 6 h of life by a 'study team' uninvolved in clinical care including decision-making. Procedure duration and the study team's words and actions during the sham treatment mimicked those of the minimally invasive surfactant therapy procedure. Post-intervention, three clinicians completed a questionnaire regarding perceived group allocation, with the responses matched against actual intervention and categorised as correct, incorrect, or unsure. Success of blinding was calculated using validated blinding indices applied to the data overall (James index, successful blinding defined as > 0.50), or to the two treatment allocation groups (Bang index, successful blinding: -0.30 to 0.30). Blinding success was measured within staff role, and the associations between blinding success and procedural duration and oxygenation improvement post-procedure were estimated. RESULTS: From 1345 questionnaires in relation to a procedural intervention in 485 participants, responses were categorised as correct in 441 (33%), incorrect in 142 (11%), and unsure in 762 (57%), with similar proportions for each of the response categories in the two treatment arms. The James index indicated successful blinding overall 0.67 (95% confidence interval (CI) 0.65-0.70). The Bang index was 0.28 (95% CI 0.23-0.32) in the minimally invasive surfactant therapy group and 0.17 (95% CI 0.12-0.21) in the sham arm. Neonatologists more frequently guessed the correct intervention (47%) than bedside nurses (36%), neonatal trainees (31%), and other nurses (24%). For the minimally invasive surfactant therapy intervention, the Bang index was linearly related to procedural duration and oxygenation improvement post-procedure. No evidence of such relationships was seen in the sham arm. CONCLUSION: Blinding of a procedural intervention from clinicians is both achievable and measurable in neonatal randomised controlled trials.

Resuscitators' opinions on using a respiratory function monitor during neonatal resuscitation.

AIM: The aim of this study was to assess the resuscitators' opinions of the usefulness and clinical value of using a respiratory function monitor (RFM) when resuscitating extremely preterm infants with positive pressure ventilation. METHODS: The link to an online survey was sent to 106 resuscitators from six countries who were involved in a multicentre trial that compared the percentage of inflations within a predefined target range with and without the RFM. The resuscitators were asked to assess the usefulness and clinical value of the RFM. The survey was online for 4 months after the trial ended in May 2019. RESULTS: The survey was completed by 74 (70%) resuscitators of which 99% considered the RFM to be helpful during neonatal resuscitation and 92% indicated that it influenced their decision-making. The majority (76%) indicated that using the RFM improved their practice and made resuscitation more effective, even when the RFM was not available. Inadequate training was the key issue that limited the effectiveness of the RFM: 45% felt insufficiently trained, and 78% felt more training in using and interpreting the RFM would have been beneficial. CONCLUSION: Resuscitators considered the RFM to be helpful to guide neonatal resuscitation, but sufficient training was required to achieve the maximum benefit.

"Harry Potter and the Multitudinous Maladies": a retrospective population-based observational study of morbidity and mortality among witches and wizards.

OBJECTIVES: To describe the prevalence of maladies and deaths among witches and wizards in the Harry Potter world, their causes, and associated therapies. DESIGN: Retrospective population-based observational study (report analysis) undertaken 10 February - 19 March 2022. SETTING: All locations described in the Harry Potter books, predominantly Hogwarts School of Witchcraft and Wizardry, but also selected locations, including Privet Drive No 4, Diagon Alley, the Ministry of Magic, and The Burrow. PARTICIPANTS: All witches and wizards mentioned at least once in any of the seven Harry Potter books. MAIN OUTCOME MEASURES: Overall numbers of maladies and deaths. Secondary outcomes were changes in morbidity and mortality over time, causes of morbidity and mortality, and treatments. RESULTS: A total of 603 wizards or witches named in the Potter books experienced 1541 maladies and injuries (1410 non-fatal) and 131 deaths. Overall morbidity incidence was 471 events per 1000 individuals, and mortality, after adjustment for Lord Voldemort's multi-mortality, was 20.6%. The most frequent causes of morbidity were traumatic injuries during duels or fights (553 cases, 39.2%), magical objects, potions, plants, or creatures (345, 24.5%), and non-combative trauma (221, 15.7%). Most deaths were related to wizarding duels (101 of 131, 77.1%). Treatments were rarely described; the most frequent were jinxes (274, 19.4%) and potions (136, 9.6%). Hospital stays were shorter than a week for almost all non-fatal maladies (1397 of 1410, 99.1%). CONCLUSIONS: Morbidity and, in particular, mortality were very high and predominantly caused by magical means. Further investigation into the safety at Hogwarts School of Witchcraft and Wizardry is warranted. The few treatments used had high success rates; rapid recovery was the rule, and hospital stays generally brief. Efforts should be undertaken to identify the magical therapies and interventions used and to introduce these novel remedies into Muggle medicine.

Tidal volumes during delivery room stabilization of (near) term infants.

BACKGROUND: We sought to assess tidal volumes in (near) term infants during delivery room stabilization. METHODS: Secondary analysis of a prospective study comparing two facemasks used for positive pressure ventilation (PPV) in newborn infants ≥ 34 weeks gestation. PPV was provided with a T-piece device with a PIP of 30 cmH2O and positive end-expiratory airway pressure of 5 cmH2O. Expired tidal volumes (Vt) were measured with a respiratory function monitor. Target range for Vt was defined to be 4 - 8 ml/kg. RESULTS: Twenty-three infants with a median (IQR) gestational age of 38.1 (36.4 - 39.0) weeks received 1828 inflations with a median Vt of 4.6 (3.3 - 6.2) ml/kg. Median Vt was in the target range in 12 infants (52%), lower in 9 (39%) and higher in 2 (9%). Thirty-six (25-27) % of the inflations were in the target rage over the duration of PPV while 42 (25 - 65) % and 10 (3 - 33) % were above and below target range. CONCLUSIONS: Variability of expiratory tidal volume delivered to term and late preterm infants was wide. Reliance on standard pressures and clinical signs may be insufficient to provide safe and effective ventilation in the delivery room. TRIAL REGISTRATION: This is a secondary analysis of a prospectively registered randomized controlled trial (ACTRN12616000768493).

Home-based detoxification for neonatal abstinence syndrome reduces length of hospital admission without prolonging treatment.

AIM: Neonatal abstinence syndrome (NAS) is a drug withdrawal syndrome, secondary to in utero chemical exposure and characterised by tremor, irritability and feed intolerance. It often requires prolonged hospital treatment and separation of families. Outpatient therapy may reduce this burden, but current literature is sparse. This review aimed to evaluate the safety and efficacy of our home-based detoxification programme and compare it with standard inpatient care. METHODS: Infants requiring treatment for NAS between January 2004 and December 2010 were reviewed. Data on demographics, drug exposure, length of stay and type of therapy were compared between infants selected for home-based therapy and those treated conventionally. RESULTS: Of the 118 infants who were admitted for treatment of NAS, 38 (32%) were managed at home. Infants receiving home-based detoxification had shorter hospital stays (mean 19 days vs. 39 days), with no increase in total duration of treatment (mean 36 days vs. 41 days), and were more likely to be breastfeeding on discharge from hospital care (45% vs. 22%). CONCLUSION: In selected infants, home-based detoxification is associated with reduced hospital stays and increased rates of breastfeeding, without prolonging therapy. Safety of the infants remains paramount, which precludes many from entering such a programme.

Cerebral Oxygenation during Neonatal Intubation with Nasal High Flow: A Sub-Study of the SHINE Randomized Trial.

INTRODUCTION: Nasal high flow (nHF) improves the likelihood of successful neonatal intubation on the first attempt without physiological instability. The effect of nHF on cerebral oxygenation is unknown. The aim of this study was to compare cerebral oxygenation during endotracheal intubation in neonates receiving nHF and those receiving standard care. METHODS: A sub-study of a multicentre randomized trial of nHF during neonatal endotracheal intubation. A subset of infants had near-infrared spectroscopy (NIRS) monitoring. Eligible infants were randomly assigned to nHF or standard care during the first intubation attempt. NIRS sensors provided continuous regional cerebral oxygen saturation (rScO2) monitoring. The procedure was video recorded, and peripheral oxygen saturation and rScO2 data were extracted at 2-second intervals. The primary outcome was the average difference in rScO2 from baseline during the first intubation attempt. Secondary outcomes included average rScO2 and rate of change of rScO2. RESULTS: Nineteen intubations were analyzed (11 nHF; 8 standard care). Median (interquartile range [IQR]) postmenstrual age was 27 (26.5-29) weeks, and weight was 828 (716-1,135) g. Median change in rScO2 from baseline was -1.5% (-5.3 to 0.0) in the nHF group and -9.4% (-19.6 to -4.5) in the standard care group. rScO2 fell more slowly in infants managed with nHF compared with standard care: median (IQR) rScO2 change -0.08 (-0.13 to 0.00) % per second and -0.36 (-0.66 to -0.22) % per second, respectively. CONCLUSIONS: In this small sub-study, regional cerebral oxygen saturation was more stable in neonates who received nHF during intubation compared with standard care.

Type 2 immune polarization is associated with cardiopulmonary disease in preterm infants.

Postnatal maturation of the immune system is poorly understood, as is its impact on illnesses afflicting term or preterm infants, such as bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension. These are both cardiopulmonary inflammatory diseases that cause substantial mortality and morbidity with high treatment costs. Here, we characterized blood samples collected from 51 preterm infants longitudinally at five time points, 20 healthy term infants at birth and age 3 to 16 weeks, and 5 healthy adults. We observed strong associations between type 2 immune polarization in circulating CD3+CD4+ T cells and cardiopulmonary illness, with odds ratios up to 24. Maternal magnesium sulfate therapy, delayed hepatitis B vaccination, and increasing fetal, but not maternal, chorioamnionitis severity were associated with attenuated type 2 polarization. Blocking type 2 mediators such as interleukin-4 (IL-4), IL-5, IL-13, or signal transducer and activator of transcription 6 (STAT6) in murine neonatal cardiopulmonary disease in vivo prevented changes in cell type composition, increases in IL-1ß and IL-13, and losses of pulmonary capillaries, but not gains in larger vessels. Thereby, type 2 blockade ameliorated lung inflammation, protected alveolar and vascular integrity, and confirmed the pathological impact of type 2 cytokines and STAT6. In-depth flow cytometry and single-cell transcriptomics of mouse lungs further revealed complex associations between immune polarization and cardiopulmonary disease. Thus, this work advances knowledge on developmental immunology and its impact on early life disease and identifies multiple therapeutic approaches that may relieve inflammation-driven suffering in the youngest patients.

Enhanced monitoring during neonatal resuscitation.

Immediately after birth through spontaneous breaths, infants' clear lung liquid replacing it with air, and gradually establishing a functional residual capacity to achieve gas exchange. Most infants start breathing independently after birth and ~3% of infants who require positive pressure ventilation. When newborns fail to start breathing the current neonatal resuscitation guidelines recommend initiatingpositive pressure ventilationusing a face mask and a ventilation device. Adequate ventilation is the cornerstone of successful neonatal resuscitation; therefore, it is mandatory that anybody involved in neonatal resuscitation is trained in mask ventilation techniques. One of the main problems with mask ventilation is that it is very subjective with direct feedback lacking and not uncommonly, the resuscitator does not realise that their technique is unsatisfactory. Many studies have shown that monitoring tidal volume and leak around the mask or endotracheal tube enables the resuscitator to identify the problem and adjust their technique to reduce the leak and deliver and appropriate tidal volume. This chapter discusses the currently available monitoring devices used during stabilization/resuscitation in the delivery room.

Smaller facemasks for positive pressure ventilation in preterm infants: A randomised trial.

AIM: Facial measurements of preterm infants indicate that standard diameter facemasks used during positive pressure ventilation are too large, which may lead to mask leak and compromise resuscitation. We aimed to determine whether the use of a facemask that better complies with the dimensions of preterm faces, compared with a standard facemask, reduces facemask leak. METHODS: Parallel group, randomised controlled trial. Preterm infants ≤32 weeks' gestation receiving facemask ventilation prior to intubation in the neonatal intensive care unit, and those 28-32+6 weeks' receiving facemask ventilation in the delivery room were eligible. Infants were randomised to receive ventilation via a standard (50mm) (control), or a smaller (35mm or 42mm) diameter facemask (intervention), stratified by gestation (≤26 weeks'; 35mm, 27-32+6; 42mm). The primary outcome was leak between the mask and the infants face. RESULTS: Of 298 eligible infants, 139 were randomised and 131 were included in the final analysis; 66 in the intervention group and 65 in the control group. The median (IQR) leak was 42% (13-69%) in the intervention group compared with 39% (22-66%) in the control group P=0.43. The median (IQR) lowest oxygen saturation was similar in both groups [intervention 70% (34-93%) vs. control 71% (40-93%) P=0.75]. One infant crossed over from the intervention to the control group due to poor response to ventilation with the intervention facemask. CONCLUSIONS: Smaller facemasks did not reduce mask leak in preterm facemask ventilation. All facemasks had high leak, particularly in infants ≤26 weeks' gestation. CLINICAL TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12614000709640, www.anzctr.org.au.

Changing gas flow during neonatal resuscitation: a manikin study.

INTRODUCTION: When using a T-piece device, resuscitators may try to improve airway pressures by increasing gas flow instead of correcting face mask position. AIM: To measure the effects of changing gas flow during positive pressure ventilation (PPV) on peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), expiratory tidal volume (V(Te)) and mask leak. METHODS: Using a Neopuff T-piece device, 20 neonatal staff members delivered PPV to a modified, leak-free manikin. Resuscitation parameters were recorded. Study A: PPV for 4 min at PIP 30 cm H(2)O and PEEP 5 cm H(2)O. Each minute gas flow was increased (5, 8, 10, and 15 L/min). PIP and PEEP settings were unchanged. Study B: same pressure settings; PPV for 1 min with 5, 8, 10, and 15 L/min in a random order, at a rate of ∼ 60/min. The pressures were adjusted to maintain the same PIP and PEEP after each flow change. RESULTS: Study A: As gas flow increased (5, 8, 10 and 15 L/min) the median PEEP increased from 4.7 to 26.4 cm H(2)O (p<0.002). Median V(Te) decreased from 10.0 to 0.8 mL (p<0.001). PIP increased slightly from 30 cm H(2)O to 36 cm H(2)O at 15 L/min (p<0.005). Mask leak increased from 14% to 98% (p<0.001) because mask pressure increased. Study B: when PIP and PEEP were maintained there were no significant differences in V(Te) (p=0.42) or mask leak (p=0.51) with changing gas flow. CONCLUSION: During PPV increasing gas flow dramatically increased PEEP and mask leak and in consequence reduced V(Te). Gas flow should rarely be changed during T-piece resuscitation.

Respiratory monitoring of neonatal resuscitation.

Video observations and recordings of respiratory signals from mannequin studies and delivery room (DR) resuscitations are described. This article discusses the uses of a respiratory function monitor (RFM) during training and resuscitations along with potential pitfalls and limitations. It adds objectivity to the clinical assessment. A respiratory function monitor provides real-time quantitative information including tidal volume and leak. It may be used to teach correct mask hold and positioning techniques during simulation-based mannequin. Examples demonstrating its potential usefulness during resuscitations are provided. However, further studies are needed to investigate whether it can help improve short-term and long-term outcomes.

Assessment of tidal volume and gas leak during mask ventilation of preterm infants in the delivery room.

AIM: The aim was to compare resuscitators' estimates of tidal volume (V(T)) and face mask leak with measured values during positive pressure ventilation (PPV) of newborn infants in the delivery room. PATIENTS AND METHODS: The authors measured inflating pressures and V(T) delivered using a respiratory function monitor, and calculated face mask leak. After 60 s of PPV, resuscitators were asked to estimate V(T) and face mask leak. These estimates were compared with measurements taken during the previous 30 s. RESULTS: The authors studied 20 infants who received a mean (SD) of 21 (6) inflations during the 30 s. The median (IQR) expired tidal volume (V(Te)) delivered was 8.7 ml/kg (5.3-11.3). V(Te) varied widely during each resuscitation and between resuscitators. Five resuscitators could not estimate V(Te), one overestimated and 14 underestimated their median delivered V(Te). The median (IQR) face mask leak was 29% (16-63%). Leak also varied widely during each resuscitation and between resuscitators. One resuscitator could not estimate mask leak, four overestimated leak and 15 underestimated leak. CONCLUSION: During face mask ventilation in the delivery room, V(T) and face mask leak were large and variable. The resuscitators were unable to accurately assess their face mask leak or delivered V(T).