Multicentre, randomised trial to investigate early nasal high-flow therapy in paediatric acute hypoxaemic respiratory failure: a protocol for a randomised controlled trial-a Paediatric Acute respiratory Intervention Study (PARIS 2).

INTRODUCTION: Acute hypoxaemic respiratory failure (AHRF) in children is the most frequent reason for non-elective hospital admission. During the initial phase, AHRF is a clinical syndrome defined for the purpose of this study by an oxygen requirement and caused by pneumonia, lower respiratory tract infections, asthma or bronchiolitis. Up to 20% of these children with AHRF can rapidly deteriorate requiring non-invasive or invasive ventilation. Nasal high-flow (NHF) therapy has been used by clinicians for oxygen therapy outside intensive care settings to prevent escalation of care. A recent randomised trial in infants with bronchiolitis has shown that NHF therapy reduces the need to escalate therapy. No similar data is available in the older children presenting with AHRF. In this study we aim to investigate in children aged 1 to 4 years presenting with AHRF if early NHF therapy compared with standard-oxygen therapy reduces hospital length of stay and if this is cost-effective compared with standard treatment. METHODS AND ANALYSIS: The study design is an open-labelled randomised multicentre trial comparing early NHF and standard-oxygen therapy and will be stratified by sites and into obstructive and non-obstructive groups. Children aged 1 to 4 years (n=1512) presenting with AHRF to one of the participating emergency departments will be randomly allocated to NHF or standard-oxygen therapy once the eligibility criteria have been met (oxygen requirement with transcutaneous saturation <92%/90% (dependant on hospital standard threshold), diagnosis of AHRF, admission to hospital and tachypnoea ≥35 breaths/min). Children in the standard-oxygen group can receive rescue NHF therapy if escalation is required. The primary outcome is hospital length of stay. Secondary outcomes will include length of oxygen therapy, proportion of intensive care admissions, healthcare resource utilisation and associated costs. Analyses will be conducted on an intention-to-treat basis. ETHICS AND DISSEMINATION: Ethics approval has been obtained in Australia (HREC/15/QRCH/159) and New Zealand (HDEC 17/NTA/135). The trial commenced recruitment in December 2017. The study findings will be submitted for publication in a peer-reviewed journal and presented at relevant conferences. Authorship of all publications will be decided by mutual consensus of the research team. TRIAL REGISTRATION NUMBER: ACTRN12618000210279.

Nasal High Flow in Room Air for Hypoxemic Bronchiolitis Infants.

Background: Bronchiolitis is the most common reason for hospital admission in infants, with one third requiring oxygen therapy due to hypoxemia. It is unknown what proportion of hypoxemic infants with bronchiolitis can be managed with nasal high-flow in room air and their resulting outcomes. Objectives and Settings: To assess the effect of nasal high-flow in room air in a subgroup of infants with bronchiolitis allocated to high-flow therapy in a recent multicenter randomized controlled trial. Patients and Interventions: Infants allocated to the high-flow arm of the trial were initially treated with room air high-flow if saturations were ≥85%. Subsequently, if oxygen saturations did not increase to ≥92%, oxygen was added and FiO2 was titrated to increase the oxygen saturations. In this planned sub-study, infants treated during their entire hospital stay with high-flow room air only were compared to infants receiving either standard-oxygen or high-flow with oxygen. Baseline characteristics, hospital length of stay and length of oxygen therapy were compared. Findings: In the per protocol analysis 64 (10%) of 630 infants commenced on high-flow room air remained in room air only during the entire stay in hospital. These infants on high-flow room air were on average older and presented with moderate hypoxemia at presentation to hospital. Their length of respiratory support and length of stay was also significantly shorter. No pre-enrolment factors could be identified in a multivariable analysis. Conclusions: In a small sub-group of hypoxemic infants with bronchiolitis hypoxemia can be reversed with the application of high-flow in room air only. Trial registration: ACTRN12615001305516.

Impact of Parent Practices of Infant Positioning on Head Orientation Profile and Development of Positional Plagiocephaly in Healthy Term Infants.

AIMS: The influence of infant positioning on the development of head orientation and plagiocephaly is not clear. This study explored the relationship between infant body and head positioning, with the development of asymmetrical head orientation and/or positional plagiocephaly. Methods: Clinician measurement of head orientation profile and parent-reported infant positioning data were collected for 94 healthy term infants at 3, 6, and 9 weeks of age. Plagiocephaly was measured at 9 weeks with the modified Cranial Vault Asymmetry Index. RESULTS: More severe plagiocephaly was associated with longer supine-sleep-maximum (p = 0.001) and longer supine-lying-total (p = 0.014) at 6 weeks. Prone positioning was not associated with plagiocephaly. Parent-reported head asymmetry during awake and sleep time at 3 weeks identified infants with clinician-measured head asymmetry at 9 weeks. Better symmetry in head turning was associated with more side-lying-total time by 9 weeks (p = 0.013). CONCLUSIONS: Our results showed that infant positioning is associated with early head orientation and plagiocephaly development. Early parent-reported asymmetry during awake and sleep time is an important indicator for the need for professional assessment and advice. A Plagiocephaly Prevention Strategy and Plagiocephaly Screening Pathway are provided for clinicians and parents.

Positional plagiocephaly is associated with sternocleidomastoid muscle activation in healthy term infants.

PURPOSE: To explore the relationship between sternocleidomastoid activation and positional plagiocephaly in healthy full term infants. METHODS: Participants were 82 infants from a regionally based-longitudinal study of infant development. Sternocleidomastoid (SCM) activation was assessed using active head-righting responses of body-on-head with and against gravity and head-on-body against gravity at 3, 6 and 9 weeks. Plagiocephaly was assessed using the Modified Cranial Vault Asymmetry Index (mCVAI) at 9 weeks. RESULTS: More severe plagiocephaly was associated with more severe asymmetry in active head-righting responses at all ages (p < 0.001). Greater right-sided occipital flatness was related to stronger contralateral/left SCM activation at 3 and at 9 weeks (p = 0.008). Greater left-sided occipital flatness was related to stronger contralateral/right SCM activation at 3 weeks (p = 0.004). In infants with any right-sided occipital flatness, the mCVAI was greater in infants with asymmetrical gravity assisted body-on-head responses at 3 weeks (mCVAI = 4.31 (2.01)%, 95% CI 2.87-5.75) compared to those with symmetrical responses (mCVAI = 2.64 (1.66)%, 95% CI 2.06-3.22) (p = 0.011). CONCLUSIONS: Sternocleidomastoid activation asymmetry is a significant contributor to plagiocephaly development by 9 weeks of age due to stronger contralateral SCM activation. Active head-righting responses are appropriate to assess sternocleidomastoid activation in infants under 2 months of age.

Clinical assessment of head orientation profile development and its relationship with positional plagiocephaly in healthy term infants - A prospective study.

BACKGROUND: Positional plagiocephaly refers to atypical development of an uneven head shape with asymmetrical head orientation as a post-natal risk factor. The development of the head orientation profile and its relationship with positional plagiocephaly are lacking. OBJECTIVES: To explore the head orientation profile development and its relationship with positional plagiocephaly in healthy full term infants. METHODS: A prospective observational study including 94 infants was conducted. Head orientation measures including head orientation duration, head orientation strength and latency to turn were conducted at three, six and nine weeks of age. Plagiocephaly outcome was measured by modified Cranial Vault Asymmetry Index at nine weeks. RESULTS: Lateral head orientation duration predominated at three weeks, mean (standard deviation) (right=40 [21.7]%; left=41 [21.5]%; midline=19 [19.9]%). It decreased bilaterally in favour of midline positioning at nine weeks (right=30 [22.3]%; left=24 [22.0]%; midline=46 [27]%. Although head orientation strength was similar across the three ages after accounting for side, head orientation strength to left was decreased from three to nine weeks (p=0.031; 95% CI: 0.12-2.06). There was a reduction in left-consistent with increase in left-bias from 3weeks to 6weeks of age (p=0.011). Positional plagiocephaly at nine weeks was associated with head orientation duration-right (p<0.001; r(2)=0.20); head orientation duration-left (p<0.001; r(2)=0.17); head orientation strength at three and six weeks (p<0.001; r(2)=0.22), but not latency to turn. CONCLUSIONS: Healthy infants show progressive change from symmetrical lateral head orientation to midline orientation from three to nine weeks. There is association of head orientation duration and strength with positional plagiocephaly.

Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children.

Background. Mycoplasma pneumoniae (M. pneumoniae) is widely recognised as an important cause of community-acquired lower respiratory tract infection (LRTI) in children. Pulmonary manifestations are typically tracheobronchitis or pneumonia but M. pneumoniae is also implicated in wheezing episodes in both asthmatic and non-asthmatic individuals. Although antibiotics are used to treat LRTIs, are view of several major textbooks offers conflicting advice for using antibiotics in the management of M. pneumoniae LRTI in children.Objectives To determine whether antibiotics are effective in the treatment of childhood LRTI secondary to M. pneumoniae infections acquired in the community.Search methods We searched CENTRAL (2014, Issue 3), MEDLINE (1966 to July week 4, 2014), EMBASE (1980 to July, 2014), and both WHOICTRP and ClinicalTrials.gov (13 August 2014).Selection criteria Randomised controlled trials (RCTs) comparing antibiotics commonly used for treating M. pneumoniae (i.e. macrolide, tetracycline or quinolone classes) versus placebo, or antibiotics from any other class in the treatment of children under 18 years of age with community acquired LRTI secondary to M. pneumoniae.Data collection and analysis The review authors independently selected trials for inclusion and assessed methodological quality. We extracted and analysed relevant data separately and resolved disagreements by consensus.Main results A total of 1912 children were enrolled from seven studies. Data interpretation was limited by the inability to extract data that referred to children with M. pneumoniae. In most studies, clinical response did not differ between children randomised to a macrolide antibiotic and children randomised to a non-macrolide antibiotic. In one controlled study (of children with recurrent respiratory infections, whose acute LRTI was associated with Mycoplasma, Chlamydia or both, by polymerase chain reaction and/or paired sera) 100% of children treated with azithromycin had clinical resolution of their illness compared to 77% not treated with azithromycin at one month. Authors' conclusions There is insufficient evidence to draw any specific conclusions about the efficacy of antibiotics for this condition in children (although one trial suggests macrolides may be efficacious in some children with LRTI secondary to Mycoplasma). The use of antibiotics has to be balanced with possible adverse events. There is still a need for high quality, double-blinded RCTs to assess the efficacy and safety of antibiotics for LRTI secondary to M. pneumoniae in children.

Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is widely recognised as an important cause of community-acquired lower respiratory tract infection (LRTI) in children. Pulmonary manifestations are typically tracheobronchitis or pneumonia but M. pneumoniae is also implicated in wheezing episodes in both asthmatic and non-asthmatic individuals. Although antibiotics are used to treat LRTIs, a review of several major textbooks offers conflicting advice for using antibiotics in the management of M. pneumoniae LRTI in children. OBJECTIVES: To determine whether antibiotics are effective in the treatment of childhood LRTI secondary to M. pneumoniae infections acquired in the community. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to February week 5, 2012) and EMBASE (1980 to March 2012). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antibiotics commonly used for treating M. pneumoniae (i.e. macrolide, tetracycline or quinolone classes) versus placebo, or antibiotics from any other class in the treatment of children under 18 years of age with community-acquired LRTI secondary to M. pneumoniae. DATA COLLECTION AND ANALYSIS: The review authors independently selected trials for inclusion and assessed methodological quality. We extracted and analysed relevant data separately. We resolved disagreements by consensus. MAIN RESULTS: A total of 1912 children were enrolled from seven studies. Data interpretation was limited by the inability to extract data that referred to children with M. pneumoniae. In most studies, clinical response did not differ between children randomised to a macrolide antibiotic and children randomised to a non-macrolide antibiotic. In one controlled study (of children with recurrent respiratory infections, whose acute LRTI was associated with Mycoplasma, Chlamydia or both by polymerase chain reaction, and/or paired sera) 100% of children treated with azithromycin had clinical resolution of their illness compared to 77% not treated with azithromycin at one month. AUTHORS' CONCLUSIONS: There is insufficient evidence to draw any specific conclusions about the efficacy of antibiotics for this condition in children (although one trial suggests macrolides may be efficacious in some children with LRTI secondary to Mycoplasma). The use of antibiotics has to be balanced with possible adverse events. There is still a need for high quality, double-blinded RCTs to assess the efficacy and safety of antibiotics for LRTI secondary to M. pneumoniae in children.

Test-retest reproducibility of the 1000 Hz tympanometry test in newborn and six-week-old healthy infants.

This study aimed to evaluate the test-retest reproducibility of the high frequency tympanometry (HFT) test measured in healthy infants. A total of 273 newborn babies (106 males and 147 females) were assessed twice (Test 1 and Test 2) on the same day, followed by two more assessments (Test 3 and Test 4) for 118 babies (48 males and 70 females) who returned six weeks later. Five HFT measures including the peak compensated static admittance and component compensated static admittance were assessed for test-retest reproducibility. The results showed no significant differences in mean values of the HFT results between the test and retest conditions for newborn (Test 1/ Test 2) and six-week-old babies (Test 3/ Test 4). High reproducibility for all HFT measures was found for both age groups, as judged by the high intra-correlation coefficients of between 0.75 and 0.95. Normal variations of the HFT measures were established using the 90% range of absolute test-retest difference. Changes in test-retest findings exceeding the 95th percentile values may be considered significant, indicating possible functional changes.

Antibiotics for community-acquired lower respiratory tract infections secondary to Mycoplasma pneumoniae in children.

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is widely recognised as an important cause of community-acquired lower respiratory tract infection (LRTI) in children. Pulmonary manifestations are typically tracheobronchitis or pneumonia but M. pneumoniae is also implicated in wheezing episodes in both asthmatic and non-asthmatic individuals. Although antibiotics are used to treat LRTI, a review of several major textbooks offers conflicting advice for using antibiotics in the management of M. pneumoniae LRTI in children. OBJECTIVES: To determine whether antibiotics are effective in the treatment of childhood LRTI secondary to M. pneumoniae infections acquired in the community. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, issue 1), which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to February 2010) and EMBASE (1980 to February 2010). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antibiotics commonly used for treating M. pneumoniae (i.e. macrolide, tetracycline or quinolone classes) versus placebo, or antibiotics from any other class in the treatment of children under 18 years of age with community-acquired LRTI secondary to M. pneumoniae. DATA COLLECTION AND ANALYSIS: The review authors independently selected trials for inclusion and assessed methodological quality. We extracted and analysed relevant data separately. Disagreements were resolved by consensus. MAIN RESULTS: A total of 1912 children were enrolled from seven studies. Data interpretation was limited by the inability to extract data that referred to children with M. pneumoniae. In most studies, clinical response did not differ between children randomised to a macrolide antibiotic and children randomised to a non-macrolide antibiotic. In one controlled study (of children with recurrent respiratory infections, whose acute LRTI was associated with Mycoplasma, Chlamydia or both by polymerase chain reaction, and/or paired sera) 100% of children treated with azithromycin had clinical resolution of their illness compared to 77% not treated with azithromycin at one month. AUTHORS' CONCLUSIONS: There is insufficient evidence to draw any specific conclusions about the efficacy of antibiotics for this condition in children (although one trial suggests macrolides may be efficacious in some children with LRTI secondary to Mycoplasma). The use of antibiotics has to be balanced with possible adverse events. There is still a need for high quality, double-blinded RCTs to assess the efficacy and safety of antibiotics for LRTI secondary to M. pneumoniae in children.

High frequency immittance findings: newborn versus six-week-old infants.

This study aimed to compare the high frequency (1 kHz) tympanometry (HFT) and acoustic reflex (AR) measures obtained from infants at birth and at 6-7 weeks of age. HFT results and AR thresholds using a 2-kHz tone and broadband noise activators were obtained from 42 healthy full-term neonates (15 boys and 27 girls) at both test sessions, separated by six weeks. The results showed that the mean values of HFT test parameters and AR thresholds obtained at 6-7 weeks were generally greater than those obtained at birth. In particular, the differences in mean values of uncompensated admittance at 200 daPa, uncompensated peak admittance, uncompensated peak susceptance, peak-compensated static admittance, and AR thresholds with a 2 kHz tone and broadband noise were found to be statistically significant. The findings from this study suggest the need to have separate sets of normative HFT and AR data for infants at birth and 6-7 weeks.

Measuring middle ear admittance in newborns using 1000 Hz tympanometry: a comparison of methodologies.

The present study aimed to compare three measures to estimate middle ear admittance in neonates using 1000 Hz tympanometry. Data were obtained from 36 full-term newborns, aged between 24 and 123 hours, who passed a transient evoked otoacoustic emissions test and assessed using a Madsen Otoflex impedance meter. The results showed that the mean middle ear admittances obtained by compensating for the susceptance and conductance components at a pressure of 200 daPa and -400 daPa (Y(CC200) = 1.00 mmho and Y(CC-400) = 1.24 mmho, respectively) were significantly greater than that using the traditional baseline compensation method (Y(BC) = 0.65 mmho). Although Y(CC-400) has attained the highest mean value, it has the lowest test-retest reliability. Hence, the component compensation approach compensated at 200 daPa holds promise as an alternative method for estimating middle ear admittance in neonates. Further research to evaluate its test performance using clinical decision theory is required to determine its clinical significance.