Welcome to the 9th EAPS Congress Programme Scheduling

Abstract Body

Medecins Sans Frontiers (MSF, Doctors Without Borders) is an NGO providing medical assistance to people affected by conflict, epidemics, disasters, or exclusion from healthcare. MSF runs projects in 48 countries worldwide.

The MSF Telemedicine breaks down geographical barriers, allowing medical teams to remotely consult a network of medical expertise. Consultations using a dedicated platform are available to the local staff 24/7 and include experts in most medical specialties, all with personal experience from field work in low and middle income countries.

Abstract Body

Over 90% of the hypoxic ischemic encephalopathy disease burden occurs in low and middle-income countries. However, therapeutic hypothermia, the standard treatment for hypoxic ischemic encephalopathy in high income countries is ineffective and potentially harmful in low and middle-income countries. In this talk I will discuss the clinical heterogeneity of infants with hypoxic ischemic encephalopathy in high income and low and middle-income countries, and why and how this affects hypothermic neuroprotection, and future directions.

Background and Aims

Complications of preterm birth result in >1 million deaths/year, mostly in low resource settings and during the first day after delivery. This trial aimed to investigate the survival and clinical effects of early kangaroo mother care (eKMC) for mild-moderately unstable neonates <2000g.

Methods

This pragmatic individually randomised clinical trial was conducted at the Gambian neonatal referral hospital. Inclusion criteria included weight <2kg and age 1-24h with stable and severely unstable neonates excluded. Allocation was to standard care (control) or KMC within 24h of admission (intervention). Primary outcome was all-cause mortality at 28 postnatal days, assessed by intention-to-treat analysis. Secondary outcomes included: time to death; hypothermia and cardiorespiratory stability (24h); breastfeeding at discharge; suspected infection (3-28d); weight gain (28d) and admission duration.

Results

Among 1,107 screened neonates, 279 were randomly assigned (May 2018 - March 2020). Two participants were lost to follow up and there were no withdrawals. 24% (34/139) of control arm died within 28d versus 21% (29/138) receiving intervention (risk ratio 0·84, 95% CI 0·55 – 1·29, p=0·423). There were no between-arm differences for secondary outcomes or serious adverse events. One-third of intervention arm reverted to standard care, due to severe instability, apnoea or jaundice. Intervention fidelity was low with median daily KMC duration 6.9h/day, versus intended 18h/day.

Conclusions

No evidence for improved survival or clinical outcomes with early KMC was identified. Implementation and safety insights have value for further intervention development and wider KMC implementation. More data is needed from varying contexts before global policy changes can be recommended.

Background and Aims

Co-existing infection/inflammation increases the risk for neonatal encephalopathy (NE) in sub-Saharan Africa (Tann 2018). Therapeutic hypothermia (HT) is ineffective in LMIC, where sentinel events are uncommon and white matter injury predominates (Thayyil 2021). In newborn piglets, we observed no protection with HT following inflammation-amplified hypoxia-ischaemia (IA-HI) (Martinello 2021). Alternative therapies are needed. Azithromycin has immunomodulatory properties and shows robust protection in the Rice-Vannucci model (Barks 2019, 2020). Our aim was to assess safety and efficacy of azithromycin in piglets after IA-HI.

Methods

Piglets underwent IA-HI injury by E. coli lipopolysaccharide pre-sensitisation, carotid artery occlusion and FiO₂ reduction. After 1h, piglets were randomised to vehicle (n=10) or azithromycin (n=7), repeated at 24h and 48h. Continuous electroencephalogram (aEEG) and ¹H Magnetic Resonance Spectroscopy Lactate/N-acetylaspartate (Lac/NAA) peak ratio were acquired at 60h. Piglets were euthanised at 65h and brain assessed by immunohistochemistry.

Results

We observed no difference in insult severity between groups. Azithromycin 20mg/kg achieved plasma levels of ~3000ng/mL with no QTc prolongation. Azithromycin reduced mean Lac/NAA by -0.17 (95%CI,-0.56-0.22) Log₁₀ units in the BGT and -0.04 (95%CI,-0.05-0.05) in the WM voxel (Figure). Bayesian analysis using non-informative priors indicated an 82.8% and 55.1% probability (Pr(superiority)) of Lac/NAA reduction in the BGT and WM respectively. On aEEG, cerebral activity at 55-60h significantly improved (Pr(Superiority)=95.5%). Azithromycin significantly suppressed microglial activation (IBA-1) in four regions (Figure).

Conclusions

Azithromycin shows promise in reducing BGT injury after IS-HI, however dose optimisation to achieve levels of 10,000ng/mL (tolerated in preterm infants) may further improve outcomes.

Study was funded by Gates Foundation (INV-002322).

Background and Aims

Background

One million neonates succumb to respiratory insufficiency each year worldwide. The novel Vayu b-CPAP System was developed to treat neonates and infants with Respiratory Distress Syndrome (RDS), pneumonia, COVID-19, and other causes of severe respiratory distress. The Vayu b-CPAP System does not require electricity or compressed air, is easy to use, is in use in 14 countries, and was granted Regulatory authorization in multiple countries.

Methods

A Mixed Methods study was conducted to assess implementation and integration of Vayu b-CPAP Systems at Muhimbili National Hospital, Tanzania; Kenyatta National Hospital, Kenya; and Ilocos Training and Regional Medical Center in the Philippines. Characteristics of all patients treated with Vayu b-CPAP Systems were collected. An interview guide was developed in an iterative fashion and snowballing was used to interview healthcare workers until thematic saturation. Interviews were transcribed, coded, and analyzed using NVivo.

Results

Across the three facilities, 704 neonates were treated with Vayu b-CPAP Systems for an average duration of 6.9 days. Survival to wean was 86% and RDS was the most common (82%) indication for b-CPAP treatment. Healthcare workers perceived Vayu b-CPAP Systems as essential for treating neonatal respiratory distress at MNH. Key reasons were: 1) Ease of use in assembly, application, maintenance, monitoring, and troubleshooting. 2) Positive patient outcomes such as reduced mortality rates. Respondents favored the devices’ ultra-low cost, portability, ability to work without electricity, and simple maintenance.

Conclusions

Healthcare workers viewed the Vayu b-CPAP Systems as essential to their clinical care and recommended them for widespread use.