AIMS: To determine the (a) diagnostic accuracy, interobserver reliability and reliable oxygen desaturation index of 4% (ODI4) score at diagnosing obstructive sleep apnoea syndrome in children and (b) correlation between the apnoea hypopnoea index (AHI) with ODI4 and oxygen nadir between both PSG and oximetry.

METHODS: This cross-sectional study included children aged 1-18 years old, undergoing a fully attended overnight PSG for suspected obstructive sleep apnoea syndrome. The Nonin 3150 WristOx2 ™ [Fig. 2] was worn simultaneously during the PSG. Poor oximetry recordings were excluded. Pulse oximetry was scored using the McGill Oximetry Score (MOS) whereby a score of 2-4 was positive for OSAS. Specificity, sensitivity, positive predictive values (PPV), negative predictive values (NPV) and interobserver reliability of the WristOx2 were calculated.

RESULTS: One hundred and sixty-two children with a mean (SD) age of 9.3 (±3.5) years (range 2 years 6 months old - 17 years old) were included after excluding 18 children (poor oximetry data [n = 16] and incomplete PSG [n = 2]). Interobserver agreement of the WristOx2 was 0.8763 (95% CI:0.80, 0.95). WristOx2 had a sensitivity 50%, specificity 96.7%, PPV 96% and NPV 53% at diagnosing OSAS. ODI4 ≥ 2 events/hour in oximetry had a sensitivity of 97.6% and negative predictive value of 85.7% at diagnosing OSA.

Methods: A total of 125 clinical isolates collected from January 2013 to May 2015 were serotyped using seven sequential multiplex polymerase chain reactions. The susceptibility of these isolates to penicillin was also investigated.

Results: Serotypes detected among the isolates were serotypes 3, 6A/B, 6C, 11/A/D/F, 15A/F, 19A, 19F, 23A, 23F, 34. Serotypes 19F and 6A/B were the most prevalent serotypes detected. Most of the S. pneumoniae were isolated from nasopharyngeal samples of children below five years of age. Majority of the isolates were penicillin susceptible. Only 5.6 per cent of the isolates were non-susceptible to penicillin, mostly of serotype 19F.

METHODS AND ANALYSIS: This multicentre, parallel, double-blind, placebo-controlled randomised trial involving seven hospitals in six cities from three different countries commenced in May 2016. Three-hundred-and-fourteen eligible Australian Indigenous, New Zealand Māori/Pacific and Malaysian children (aged 0.25 to 5 years) hospitalised for community-acquired, chest X-ray (CXR)-proven pneumonia are being recruited. Following intravenous antibiotics and 3 days of amoxicillin-clavulanate, they are randomised (stratified by site and age group, allocation-concealed) to receive either: (i) amoxicillin-clavulanate (80 mg/kg/day (maximum 980 mg of amoxicillin) in two-divided doses or (ii) placebo (equal volume and dosing frequency) for 8 days. Clinical data, nasopharyngeal swab, bloods and CXR are collected. The primary outcome is the proportion of children without chronic respiratory symptom/signs of bronchiectasis at 24 months. The main secondary outcomes are 'clinical cure' at 4 weeks, time-to-next respiratory-related hospitalisation and antibiotic resistance of nasopharyngeal respiratory bacteria.

ETHICS AND DISSEMINATION: The Human Research Ethics Committees of all the recruiting institutions (Darwin: Northern Territory Department of Health and Menzies School of Health Research; Auckland: Starship Children's and KidsFirst Hospitals; East Malaysia: Likas Hospital and Sarawak General Hospital; Kuala Lumpur: University of Malaya Research Ethics Committee; and Klang: Malaysian Department of Health) have approved the research protocol version 7 (13 August 2018). The RCT and other results will be submitted for publication.

METHODS: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment.

RESULTS: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group.

CONCLUSIONS: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score.