Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

Sex differences in preterm respiratory morbidity: A recent whole-population study.

AIM: To determine whether there were differences between male and female infants in respiratory morbidity in a whole population of extremely preterm infants, including infants born below 24 weeks of gestation. METHODS: Retrospective whole-population study of all infants <28 weeks of gestation admitted to a neonatal unit in England from 2014 to 2019. Bronchopulmonary dysplasia (BPD) development was defined as any respiratory support at 36 weeks postmenstrual age. RESULTS: The 11 844 infants had a median (IQR) gestational age of 26.0 (24.9-27.1) weeks and a birth weight of 0.81 (0.67-0.96) kg. The duration of invasive ventilation was longer in male compared to female infants who were born at 24-27 completed weeks of gestation (p < 0.001), but not significantly different between male and female infants born at 22 and 23 weeks of gestation (p = 0.446). The incidence of BPD was higher in male compared to female infants born at 24-27 weeks of gestation (p < 0.001) but not different between male and female infants born at 22 and 23 weeks of gestation (p = 0.148). CONCLUSION: Respiratory morbidity was more pronounced in male compared to female extremely preterms, only in gestations 24-27 completed weeks. Male predominance was absent in infants born below 24 weeks of gestation.

Monitoring persistent pulmonary hypertension of the newborn using the arterial to end tidal carbon dioxide gradient.

Persistent pulmonary hypertension of the newborn (PPHN) can be monitored theoretically by the difference of the partial pressure of arterial (PaCO2) to end-tidal CO2 (EtCO2). We aimed to test the hypothesis that the PaCO2-EtCO2 gradient in infants with PPHN would be higher compared to infants without PPHN. Prospective, observational study of term-born ventilated infants with echocardiographically-confirmed PPHN with right-to-left shunting and term-born control infants without respiratory disease. The PaCO2-EtCO2 gradient was calculated as the difference between the PaCO2 measured from indwelling arterial sample lines and EtCO2 measured by continuous Microstream sidestream capnography. Twenty infants (9 with PPHN and 11 controls) were studied with a median (IQR) gestational age of 39.5 (38.7-40.4) weeks, a birthweight of 3.56 (3.15-3.93) kg and a birthweight z-score of 0.03 (- 0.91 to 1.08). The PaCO2-EtCO2 gradient was larger in the infants with PPHN compared to those without PPHN after adjusting for differences in the mean airway pressure and fraction of inspired oxygen (adjusted p = 0.037). In the infants with PPHN the median PaCO2-EtCO2 gradient decreased from 10.7 mmHg during the acute illness to 3.3 mmHg pre-extubation. The median difference in the gradient was significantly higher in infants with PPHN (6.2 mmHg) compared to infants without PPHN (-3.2 mmHg, p = 0.022). The PaCO2-EtCO2 gradient was higher in infants with PPHN compared to term born infants without PPHN and decreased over the first week of life in infants with PPHN. The gradient might be utilised to monitor the evolution and resolution of PPHN.

Islet-specific CD8+ T cells gain effector function in the gut lymphoid tissues via bystander activation not molecular mimicry.

Type 1 diabetes (T1D) is caused by aberrant activation of autoreactive T cells specific for the islet beta cells. How islet-specific T cells evade tolerance to become effector T cells is unknown, but it is believed that an altered gut microbiota plays a role. Possible mechanisms include bystander activation of autoreactive T cells in the gut or "molecular mimicry" from cross-reactivity between gut microbiota-derived peptides and islet-derived epitopes. To investigate these mechanisms, we use two islet-specific CD8+ T cell clones and the non-obese diabetic mouse model of type 1 diabetes. Both insulin-specific G9C8 cells and IGRP-specific 8.3 cells underwent early activation and proliferation in the pancreatic draining lymph nodes but not in the Peyer's patches or mesenteric lymph nodes. Mutation of the endogenous epitope for G9C8 cells abolished their CD69 upregulation and proliferation, ruling out G9C8 cell activation by a gut microbiota derived peptide and molecular mimicry. However, previously activated islet-specific effector memory cells but not naïve cells migrated into the Peyer's patches where they increased their cytotoxic function. Oral delivery of butyrate, a microbiota derived anti-inflammatory metabolite, reduced IGRP-specific cytotoxic function. Thus, while initial activation of islet-specific CD8+ T cells occurred in the pancreatic lymph nodes, activated cells trafficked through the gut lymphoid tissues where they gained additional effector function via non-specific bystander activation influenced by the gut microbiota.

Functional morphometry: non-invasive estimation of the alveolar surface area in extremely preterm infants.

BACKGROUND: The main pathophysiologic characteristic of chronic respiratory disease following extremely premature birth is arrested alveolar growth, which translates to a smaller alveolar surface area (SA). We aimed to use non-invasive measurements to estimate the SA in extremely preterm infants. METHODS: Paired measurements of the fraction of inspired oxygen and transcutaneous oxygen saturation were used to calculate the ventilation/perfusion ratio, which was translated to SA using Fick's law of diffusion. The SA was then adjusted using volumetric capnography. RESULTS: Thirty infants with a median (range) gestational age of 26.3 (22.9-27.9) weeks were studied. The median (range) adjusted SA was 647.9 (316.4-902.7) cm2. The adjusted SA was lower in the infants who required home oxygen [637.7 (323.5-837.5) cm2] compared to those who did not [799.1 (444.2-902.7) cm2, p = 0.016]. In predicting the need for supplemental home oxygen, the adjusted SA had an area under the receiver operator characteristic curve of 0.815 (p = 0.017). An adjusted SA ≥688.6 cm2 had 86% sensitivity and 77% specificity in predicting the need for supplemental home oxygen. CONCLUSIONS: The alveolar surface area can be estimated non-invasively in extremely preterm infants. The adjusted alveolar surface area has the potential to predict the subsequent need for discharge home on supplemental oxygen. IMPACT: We describe a novel biomarker of respiratory disease following extremely preterm birth. The adjusted alveolar surface area index was derived by non-invasive measurements of the ventilation/perfusion ratio and adjusted by concurrent measurements of volumetric capnography. The adjusted alveolar surface area was markedly reduced in extremely preterm infants studied at 7 days of life and could predict the need for discharge home on supplemental oxygen. This method could be used at the bedside to estimate the alveolar surface area and provide an index of the severity of lung disease, and assist in monitoring, clinical management and prognosis.

Ventilatory response to added dead space in infants exposed to second-hand smoke in pregnancy.

Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control. In utero nicotine exposure has been shown to blunt the infant ventilatory response to hypercapnia, which could increase the risk of sudden infant death syndrome. The potential impact of maternal second-hand smoke exposure, however, has not yet been determined. The aim of this study was to assess ventilatory response to added dead-space (inducing hypercapnia) in infants with second-hand smoke exposure during pregnancy, in infants whose mothers smoked and in controls (non-smoke exposed). Infants breathed through a face mask and specialised "tube-breathing" circuit, incorporating a dead space of 4.4 ml/kg body weight. The maximum minute ventilation (MMV) during added dead space breathing was determined and the time taken to achieve 63% of the MMV calculated (the time constant (TC) of the response). Infants were studied on the postnatal ward prior to discharge home. Thirty infants (ten in each group) were studied with a median gestational age of 39 [range 37-41] weeks, birthweight of 3.1 [2.2-4.0] kg, and postnatal age of 33 (21-62) h. The infants whose mothers had second-hand smoke exposure (median TC 42 s, p = 0.001), and the infants of cigarette smoking mothers (median TC 37 s, p = 0.002) had longer time constants than the controls (median TC 29 s). There was no significant difference between the TC of the infants whose mothers had second-hand smoke exposure and those whose mothers smoked (p = 0.112).    Conclusion: Second-hand smoke exposure during pregnancy was associated with a delayed newborn ventilatory response. What is Known: • Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control. • The potential impact of maternal second-hand smoke exposure, however, has not yet been determined. What is New: • We have assessed the ventilatory response to added dead-space (inducing hypercapnia) in newborns with second-hand smoke exposure during pregnancy, in infants whose mothers smoked, and in controls (non-smoke exposed). • Maternal second-hand smoke exposure, as well as maternal smoking, during pregnancy was associated with a delayed newborn ventilatory response.

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.

Tolerance induction by liposomes targeting a single CD8 epitope IGRP206-214 in a model of type 1 diabetes is impeded by co-targeting a CD4+ islet epitope.

The autoimmune disease type 1 diabetes is predominantly mediated by CD8+ cytotoxic T-cell destruction of islet beta cells, of which islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)206-214 is a dominant target antigen specificity. Previously, we found that a liposome-based antigen-specific immunotherapy encapsulating the CD4+ T-cell islet epitope 2.5mim together with the nuclear factor-κB inhibitor calcitriol induced regulatory T cells and protected from diabetes in NOD mice. Here we investigated whether the same system delivering IGRP206-214 could induce antigen-specific CD8+ T-cell-targeted immune regulation and delay diabetes. Subcutaneous administration of IGRP206-214 /calcitriol liposomes transiently activated and expanded IGRP-specific T-cell receptor transgenic 8.3 CD8+ T cells. Liposomal co-delivery of calcitriol was required to optimally suppress endogenous IGRP-specific CD8+ T-cell interferon-γ production and cytotoxicity. Concordantly, a short course of IGRP206-214 /calcitriol liposomes delayed diabetes progression and reduced insulitis. However, when IGRP206-214 /calcitriol liposomes were delivered together with 2.5mim /calcitriol liposomes, disease protection was not observed and the regulatory effect of 2.5mim /calcitriol liposomes was abrogated. Thus, tolerogenic liposomes that target either a dominant CD8+ or a CD4+ T-cell islet epitope can delay diabetes progression but combining multiple epitopes does not enhance protection.

Volumetric capnography pre- and post-surfactant during initial resuscitation of premature infants.

BACKGROUND: Volumetric capnography allows for continuous monitoring of expired tidal volume and carbon dioxide. The slope of the alveolar plateau of the capnogram (SIII) could provide information regarding ventilation homogeneity. We aimed to assess the feasibility of measuring SIII during newborn resuscitation and determine if SIII decreased after surfactant indicating ventilation inhomogeneity improvement. METHODS: Respiratory function traces of preterm infants resuscitated at birth were analysed. Ten capnograms were constructed for each infant: five pre- and post-surfactant. If a plateau was present SIII was calculated by regression analysis. RESULTS: Thirty-six infants were included, median gestational age of 28.7 weeks and birth weight of 1055 g. Average time between pre- and post-surfactant was 3.2 min. Three hundred and sixty capnograms (180 pre and post) were evaluated. There was adequate slope in 134 (74.4%) capnograms pre and in 100 (55.6%) capnograms post-surfactant (p = 0.004). Normalised for tidal volume SIII pre-surfactant was 18.89 mmHg and post-surfactant was 24.86 mmHg (p = 0.006). An increase in SIII produced an up-slanting appearance to the plateau indicating regional obstruction. CONCLUSION: It was feasible to evaluate the alveolar plateau pre-surfactant in preterm infants. Ventilation inhomogeneity increased post-surfactant likely due to airway obstruction caused by liquid surfactant present in the airways. IMPACT: Volumetric capnography can be used to assess homogeneity of ventilation by SIII analysis. Ventilation inhomogeneity increased immediately post-surfactant administration during the resuscitation of preterm infants, producing a characteristic up-slanting appearance to the alveolar plateau. The best determinant of alveolar plateau presence in preterm infants was the expired tidal volume.

Diaphragmatic electromyography during a spontaneous breathing trial to predict extubation failure in preterm infants.

BACKGROUND: Premature attempts at extubation and prolonged episodes of ventilatory support in preterm infants have adverse outcomes. The aim of this study was to determine whether measuring the electrical activity of the diaphragm during a spontaneous breathing trial (SBT) could predict extubation failure in preterm infants. METHODS: When infants were ready for extubation, the electrical activity of the diaphragm was measured by transcutaneous electromyography (EMG) before and during a SBT when the infants were on endotracheal continuous positive airway pressure. RESULTS: Forty-eight infants were recruited (median (IQR) gestational age of 27.2 (25.6-30.4) weeks). Three infants did not pass the SBT and 13 failed extubation. The amplitude of the EMG increased during the SBT [2.3 (1.5-4.2) versus 3.5 (2.1-5.3) µV; p < 0.001]. In the whole cohort, postmenstrual age (PMA) was the strongest predictor for extubation failure (area under the curve (AUC) 0.77). In infants of gestational age <29 weeks, the percentage change of the EMG predicted extubation failure with an AUC of 0.74 while PMA was not associated with the outcome of extubation. CONCLUSIONS: In all preterm infants, PMA was the strongest predictor of extubation failure; in those born <29 weeks of gestation, diaphragmatic electromyography during an SBT was the best predictor of extubation failure. IMPACT: Composite assessments of readiness for extubation may be beneficial in the preterm population. Diaphragmatic electromyography measured by surface electrodes is a non-invasive technique to assess the electrical activity of the diaphragm. Postmenstrual age was the strongest predictor of extubation outcome in preterm infants. The change in diaphragmatic activity during a spontaneous breathing trial in extremely prematurely born infants can predict subsequent extubation failure with moderate sensitivity and specificity.

Regulatory T Cells Induced by Single-Peptide Liposome Immunotherapy Suppress Islet-Specific T Cell Responses to Multiple Antigens and Protect from Autoimmune Diabetes.

Ag-specific tolerizing immunotherapy is considered the optimal strategy to control type 1 diabetes, a childhood disease involving autoimmunity toward multiple islet antigenic peptides. To understand whether tolerizing immunotherapy with a single peptide could control diabetes driven by multiple Ags, we coencapsulated the high-affinity CD4+ mimotope (BDC2.5mim) of islet autoantigen chromogranin A (ChgA) with or without calcitriol (1α,25-dihydroxyvitamin D3) into liposomes. After liposome administration, we followed the endogenous ChgA-specific immune response with specific tetramers. Liposome administration s.c., but not i.v., induced ChgA-specific Foxp3+ and Foxp3- PD1+ CD73+ ICOS+ IL-10+ peripheral regulatory T cells in prediabetic mice, and liposome administration at the onset of hyperglycemia significantly delayed diabetes progression. After BDC2.5mim/calcitriol liposome administration, adoptive transfer of CD4+ T cells suppressed the development of diabetes in NOD severe combined immunodeficiency mice receiving diabetogenic splenocytes. After BDC2.5mim/calcitriol liposome treatment and expansion of ChgA-specific peripheral regulatory T cells. IFN-γ production and expansion of islet-specific glucose-6-phosphatase catalytic subunit-related protein-specific CD8+ T cells were also suppressed in pancreatic draining lymph node, demonstrating bystander tolerance at the site of Ag presentation. Thus, liposomes encapsulating the single CD4+ peptide, BDC2.5mim, and calcitriol induce ChgA-specific CD4+ T cells that regulate CD4+ and CD8+ self-antigen specificities and autoimmune diabetes in NOD mice.

Work of breathing at different tidal volume targets in newborn infants with congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) results in varying degrees of pulmonary hypoplasia. Volume targeted ventilation (VTV) is a lung protective strategy but the optimal target tidal volume in CDH infants has not previously been studied. The aim of this study was to test the hypothesis that low targeted volumes would be better in CDH infants as determined by measuring the work of breathing (WOB) in CDH infants, at three different targeted tidal volumes. A randomised cross-over study was undertaken. Infants were eligible for inclusion in the study after surgical repair of their diaphragmatic defect. Targeted tidal volumes of 4, 5, and 6 ml/kg were each delivered in random order for 20-min periods with 20-min periods of baseline ventilation between. WOB was assessed and measured by using the pressure-time product of the diaphragm (PTPdi). Nine infants with a median gestational age at birth of 38 + 4 (range 36 + 4-40 + 6) weeks and median birth weight 3202 (range 2855-3800) g were studied. The PTPdi was higher at 4 ml/kg than at both 5, p = 0.008, and 6 ml/kg, p = 0.012. CONCLUSION: VTV of 4 ml/kg demonstrated an increased PTPdi compared to other VTV levels studied and should be avoided in post-surgical CDH infants. WHAT IS KNOWN: • Lung injury secondary to mechanical ventilation increases the mortality and morbidity of infants with CDH. • Volume targeted ventilation (VTV) reduces 'volutrauma' and ventilator-induced lung injury in other neonatal intensive care populations. WHAT IS NEW: • A randomised cross-over trial was carried out investigating the response to different VTV levels in infants with CDH. • Despite pulmonary hypoplasia being a common finding in CDH, a VTV of 5ml/kg significantly reduced the work of breathing in infants with CDH compared to a lower VTV level.

The impact of COVID-19 on smoking cessation in pregnancy.

OBJECTIVES: A greater proportion of non-pregnant smokers attempted to stop smoking during compared to before the COVID-19 pandemic. The objective of this study was to determine if a greater proportion of pregnant women also attempted to stop smoking during the pandemic rather than before. METHODS: The use of antenatal smoking cessation services and nicotine replacement therapies (NRT) in pregnant women was audited before (2019-2020) and during the COVID pandemic (2020-2021). Anonymised data from January 2019 to March 2021 were analysed from the Lambeth and Southwark smoking cessation service. RESULTS: A total of 252 pregnant women who smoked were referred to their local antenatal smoking cessation service, of which 90 (35.7%) (median age: 31 years [19-52 years]) chose to attend smoking cessation clinics. The COVID-19 pandemic was not associated with an increase in the number of women attending smoking cessation clinics, (2020-2021 n=46 [40.8%] of 110); compared to (2019-2020 n=44 [30.9%] of 142 referred pregnant women pre-pandemic) p=0.061. Eighty-two women utilised NRT to help them stop smoking and the frequency of NRT use did not change during the pandemic (2019-2020 n=39, 2020-2021 n=43; p=0.420). No significant difference in smoking cessation rates between the two periods was observed at either the four-week (p=0.285) or twelve-week follow-up (p=0.829). CONCLUSIONS: Smoking cessation rates in pregnant women and the demand for antenatal smoking cessation services was unchanged during compared to before the COVID-19 pandemic.

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.

A Provider Perspective of Psychosocial Predictors of Upper-Extremity Vascularized Composite Allotransplantation Success.

PURPOSE: We performed a qualitative study to understand the psychosocial factors associated with success in upper-extremity vascularized composite allotransplantation from the perspective of transplant providers. METHODS: We recruited 13 providers actively involved in upper-extremity vascularized composite allotransplantation. Participants included physicians, nurses, social workers, occupational therapists, and research administrators. We conducted semistructured face-to-face focus group interviews using a guide that explored providers' perceptions of qualities contributing to transplant outcome. Topics included social support networks and their influence on recovery, barriers to treatment compliance and successful posttransplant rehabilitation, and the process of setting patients' expectations. We performed a thematic analysis that produced a list of themes, subthemes, and proposed hypotheses explaining how the themes related to the study's guiding questions. RESULTS: The analysis identified numerous factors that contribute to transplant success: (1) recipients' prior experiences modify their ability to cope and adapt after transplantation, (2) behaviors and characteristics such as positivity influence candidacy and may be predictive of successful outcomes, and (3) social support is essential for improved function and compliance. The provider care team cited difficulty in predicting recipient compliance and in setting realistic expectations. CONCLUSIONS: Motivated recipients with developed coping and resiliency, a positive attitude, and stable, physically-able caregivers are perceived by providers to have greater success after transplantation. CLINICAL RELEVANCE: Findings from this work may help providers determine optimal candidates for upper-extremity vascularized composite allotransplantation.

Provider perspectives on the provision of safe, equitable, trauma-informed care for intimate partner violence survivors during the COVID-19 pandemic: a qualitative study.

BACKGROUND: Early research suggests the COVID-19 pandemic worsened intimate partner violence (IPV) in the US. In particular, stay-at-home orders and social distancing kept survivors in close proximity to their abusers and restricted access to resources and care. We aimed to understand and characterize the impact of the pandemic on delivery of IPV care in Boston. METHODS: We conducted individual interviews with providers of IPV care and support in the Greater Boston area, including healthcare workers, social workers, lawyers, advocates, and housing specialists, who continued to work during the COVID-19 pandemic. Using thematic analysis, we identified themes describing the challenges and opportunites providers faced in caring for survivors during the pandemic. RESULTS: Analysis of 18 interviews yielded four thematic domains, encompassing 18 themes and nine sub-themes. Thematic analysis revealed that the pandemic posed an increased threat to survivors of IPV by exacerbating external stressors and leading to heightened violence. On a system level, the pandemic led to widespread uncertainty, strained resources, amplified inequities, and loss of community. On an individual level, COVID-19 restrictions limited survivors' abilities to access resources and to be safe, and amplified pre-existing inequities, such as limited technology access. Those who did not speak English or were immigrants experienced even more difficulty accessing resources due to language and/or cultural barriers. To address these challenges, providers utilized video and telephone interactions, and stressed the importance of creativity and cooperation across different sectors of care. CONCLUSIONS: While virtual care was essential in allowing providers to care for survivors, and also allowed for increased flexibility, it was not a panacea. Many survivors faced additional obstacles to care, such as language barriers, unequal access to technology, lack of childcare, and economic insecurity. Providers addressed these barriers by tailoring services and care modalities to an individual's needs and circumstances. Going forward, some innovations of the pandemic period, such as virtual interactions and cooperation across care sectors, may be utilized in ways that attend to shifting survivor needs and access, thereby improving safe, equitable, and trauma-informed IPV care.

Duration of mechanical ventilation and prediction of bronchopulmonary dysplasia and home oxygen in extremely preterm infants.

AIM: To determine whether the duration of invasive ventilation predicted the development of bronchopulmonary dysplasia (BPD) and need for discharge home on supplementary oxygen in extremely preterm infants. METHODS: Retrospective whole-population study of all infants <28 weeks of gestation admitted to a neonatal unit in England between 2014 and 2018. BPD development was defined as any respiratory support at 36 weeks postmenstrual age. The performance of the duration of mechanical ventilation to predict BPD or discharge home on oxygen was assessed by receiver operator characteristic curve analysis. RESULTS: The 11,806 infants had a median (IQR) gestational age of 26.0(24.9-27.1) weeks and birthweight of 0.81(0.67-0.96) kg. At discharge from neonatal care, 9,415 infants (79.7%) were alive. The incidence of BPD was 57.5% and of home oxygen 29.4%. Mechanical ventilation duration had areas under the curve of 0.793 and 0.703 in predicting BPD and home oxygen, respectively. Mechanical ventilation for >8 days predicted BPD development with 71% sensitivity and 71% specificity and mechanical ventilation for >10 days predicted discharge on home oxygen with 66% sensitivity and 65% specificity. CONCLUSION: In extremely preterm infants, the duration of invasive support predicted BPD and need for home oxygen with moderate sensitivity and specificity.

A randomised crossover trial of closed loop automated oxygen control in preterm, ventilated infants.

AIM: To determine whether closed loop automated oxygen control resulted in a reduction in the duration and severity of desaturation episodes and the number of blood gases and chest radiographs in preterm, ventilated infants. METHODS: Infants were studied on two consecutive days for 12 hours on each day. They were randomised to receive standard care (standard period) or standard care with a closed loop automated oxygen control system (automated oxygen control period) first. RESULTS: Twenty-four infants with a median gestational age of 25.7 (range 23.1-32.6) weeks were studied at a median postconceptional age of 27.4 (range 24.3-34.9) weeks. During the automated oxygen control period, there were fewer desaturations that lasted >30 seconds (P = .032) or >60 seconds (P = .002), infants spent a higher proportion of the time within their target SpO2 range during the automated oxygen control period (P < .001), and fewer manual adjustments were made to the inspired oxygen concentration (mean 0.58 vs mean 11.29) (P < .001). There were no significant differences in the number of blood gases (P = .872) or chest radiographs (P = .366) between the two periods. CONCLUSION: Closed loop automated oxygen delivery resulted in fewer prolonged desaturations with more time spent in the targeted oxygen range.

The effect of postnatal corticosteroids on growth parameters in infants with bronchopulmonary dysplasia.

OBJECTIVES: Corticosteroids are administered to ventilator dependent infants with bronchopulmonary dysplasia (BPD) to improve respiratory function and facilitating extubation. Acutely, however, growth impairment can occur as a side effect of such therapy. We aimed to determine the effect of corticosteroids on postnatal growth during the entire neonatal intensive care unit (NICU) admission. METHODS: A whole population study of extremely preterm infants with BPD was undertaken. Corticosteroid therapy was classified as treatment with dexamethasone or hydrocortisone for a least five consecutive days. Growth was calculated as the difference in weight and head circumference z-score from birth to discharge. RESULTS: Six thousand, one hundred and four infants with BPD were included of whom 28.3% received postnatal corticosteroids. Infants receiving corticosteroids were less mature (GA 25.0 vs. 26.3 weeks) and of lower birthweight (0.70 vs. 0.84 kg) than those not receiving treatment. There were no significant differences between those who did and did not receive corticosteroids in weight gain (p=0.61) or head circumference growth (p=0.33) from birth to discharge. Single vs. multiple courses of postnatal corticosteroids did not result in significant differences in weight (p=0.62) or head circumference (p=0.13) growth. CONCLUSIONS: Postnatal corticosteroid treatment did not affect the longer term growth of preterm infants with BPD.

The impact of transfers from neonatal intensive care to paediatric intensive care.

OBJECTIVES: Infants receiving care from neonatal intensive care unit (NICU) can develop chronic problems and be transferred to a paediatric intensive care unit (PICU) for on-going care. There is concern that such infants may take up a large amount of PICU resource, but this is not evidence based. We determined the impact of such transfers. METHODS: We reviewed 10 years of NICU admissions to two tertiary PICUs, which had approximately 12,000 admissions during that period. RESULTS: Sixty-seven infants, gestational age at birth 34.7 (IQR 27.1-38.8) weeks and postnatal age on transfer 81 (IQR 9-144) days were admitted from NICUs. The median (IQR) length of stay was 12 (4-41) days. The 19 infants born <28 weeks of gestation had a greater median length of stay (32, range IQR 10-93 days) than more mature born infants (7.5, IQR 4-26 days) (p=0.003). The median cost of PICU stay for NICU transfers was £23,800 (range 1,205-1,034,000) per baby. The total cost of care for infants transferred from NICUs was £6,457,955. CONCLUSIONS: Infants transferred from NICUs were a small proportion of PICU admissions but, particularly those born <28 weeks of gestation, had prolonged stays which needs to be considered when determining bed capacity.