Cognitive parameters in children with mild obstructive sleep disordered breathing.

PURPOSE: Sleep disordered breathing (SDB) in children is commonly described as a continuum from primary snoring (PS) to obstructive sleep apnea (OSA), based on apnea indices from polysomnography (PSG). This study evaluated the difference in neurocognitive and behavioral parameters, prior to treatment, in symptomatic pre-school children with PSG-diagnosed OSA and PS. METHODS: All children had positive Pediatric Sleep Questionnaire (PSQ) results and were deemed suitable for adenotonsillectomy by an ENT surgeon. Neurocognitive and behavioral data were analyzed in pre-school children at recruitment for the POSTA study (The Pre-School OSA Tonsillectomy Adenoidectomy Study). Data were compared between PS and OSA groups, with Obstructive Apnea-Hypopnea Index, OAHI < 1/h or 1-10/h, respectively. RESULTS: Ninety-one children were enrolled, including 52 with OSA and 39 with PS. Distribution of IQ (using Brief Intellectual Ability, BIA) was slightly skewed towards higher values compared with the reference population. No significant differences were found in neurocognitive or behavioral parameters for children with OSA versus those with PS. DISCUSSION: Neurocognitive and behavioral parameters were similar in pre-school children symptomatic for OSA, regardless of whether or not PSG diagnosed PS or OSA. Despite having identical symptoms, children with PS on PSG are often treated conservatively, whereas those with OSA on PSG are considered for adenotonsillectomy. This study demonstrates that, regardless of whether or not PS or OSA is diagnosed on PSG, symptoms, neurocognition, and behavior are identical in these groups. We conclude that symptoms and behavioral disturbances should be considered in addition to OAHI when determining the need for treatment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials registration number ACTRN12611000021976.

Impact of paediatric tonsillectomy perioperative management on pain, nausea and recovery: A prospective cohort study.

AIM: Tonsillectomy procedures are a core element of paediatrics; however, perioperative management differs. This study aimed to describe tonsillectomy management, including the burden of pain, nausea and delayed recovery. METHODS: A prospective cohort study was undertaken through an audit of tonsillectomy perioperative practice and recovery and survey interviews with family members 7-14 days post-surgery. The study was undertaken at an Australian tertiary referral paediatric hospital between June and September 2016. RESULTS: The audit included 255 children undergoing tonsillectomy, with 127 family members interviewed. Most participants underwent adenotonsillectomy (n = 216; 85%), with a primary diagnosis of obstructive sleep apnoea (n = 205; 80%) and a mean age of 7 years (standard deviation; 3.9). A variety of intra-operative pain relief and antiemetics was administered. Pain was present in 29% (n = 26) of participants at ward return, increasing to 32-45% at 4-20 h and decreasing to 21% (n = 15) at discharge. A third of the children (32%; n = 41) had moderate to severe pain at post-discharge interview, and 30% (n = 38) experienced nausea at home. Most parents (82%; n = 104) were still giving regular paracetamol at 7 days post-operatively, and 31% (n = 39) had finished their oxycodone. Of the participants, 14% (n = 26) presented to the emergency department within 7 days of discharge; 8% (n = 20) of the total cohort were re-admitted. CONCLUSIONS: There was variety in perioperative and post-discharge care. Pain scores were infrequently documented post-tonsillectomy, and parents are generally dissatisfied with the management of post-operative pain and nausea. Further research is needed to provide a more consistent approach to perioperative management to promote recovery.

Mouse Metanephric Mesenchymal Cell-Derived Angioblasts Undergo Vasculogenesis in Three-Dimensional Culture.

In vitro models for the investigation of renal vascular development are limited. We previously showed that isolated metanephric mesenchymal (MM) and ureteric bud (UB) cells grown in three-dimensional (3D) matrices formed organoids that consisted of primitive vascular structures surrounding a polarized epithelium. Here, we examined the potential of two principal effectors of vasculogenesis, vascular endothelial growth factor A (VEGF-A), and platelet-derived growth factor B chain (PDGF-BB), to stimulate MM cell differentiation. The results showed that MM cells possess angioblast characteristics by expressing phenotypic markers for endothelial and mesenchymal cells. UB cells synthesize VEGF-A and PDGF-BB proteins and RNA, whereas the MM cells express the respective cognate receptors, supporting their role in directional induction of vasculogenesis. VEGF-A stimulated proliferation of MM cells in monolayer and in 3D sponges but did not affect MM cell migration, organization, or vasculogenesis. However, PDGF-BB stimulated MM cell proliferation, migration, and vasculogenesis in monolayer and organization of the cells into primitive capillary-like assemblies in 3D sea sponge scaffolds in vitro. A role for PDGF-BB in vasculogenesis in the 3D MM/UB co-culture system was validated by direct interference with PDGF-BB or PDGF receptor-ß cell interactions to implicate PDGF-BB as a primary effector of MM cell vasculogenesis. Thus, MM cells resemble early renal angioblasts that may provide an ideal platform for the investigation of renal vasculogenesis in vitro.

A Prospective Study of the Incidence of Juvenile-Onset Recurrent Respiratory Papillomatosis After Implementation of a National HPV Vaccination Program.

Background: Recurrent respiratory papillomatosis is a rare but morbid disease caused by human papillomavirus (HPV) types 6 and 11. Infection is preventable through HPV vaccination. Following an extensive quadrivalent HPV vaccination program (females 12-26 years in 2007-2009) in Australia, we established a method to monitor incidence and demographics of juvenile-onset recurrent respiratory papillomatosis (JORRP) cases. Methods: The Australian Paediatric Surveillance Unit undertakes surveillance of rare pediatric diseases by contacting practitioners monthly. We enrolled pediatric otorhinolaryngologists and offered HPV typing. We report findings for 5 years to end 2016. Results: The average annual incidence rate was 0.07 per 100000. The largest number of cases was reported in the first year, with decreasing annual frequency thereafter. Rates declined from 0.16 per 100000 in 2012 to 0.02 per 100000 in 2016 (P = .034). Among the 15 incident cases (60% male), no mothers were vaccinated prepregnancy, 20% had maternal history of genital warts, and 60% were first born; 13/15 were born vaginally. Genotyped cases were HPV-6 (n = 4) or HPV-11 (n = 3). Conclusion: To our knowledge, this is the first report internationally documenting decline in JORRP incidence in children following a quadrivalent HPV vaccination program.

Rationale for and design of the "POSTA" study: Evaluation of neurocognitive outcomes after immediate adenotonsillectomy compared to watchful waiting in preschool children.

BACKGROUND: IQ deficits are linked to even mild obstructive sleep apnoea (OSA) in children. Although OSA is commonly first diagnosed in the pre-school age group, a randomised trial is still needed to assess IQ outcomes after adenotonsillectomy in the pre-school age-group. This randomised control trial (RCT) will primarily determine whether adenotonsillectomy improves IQ compared to no adenotonsillectomy after 12 months, in preschool (3-5 year-old) children with mild to moderate OSA. METHODS: This protocol is for an ongoing multi-centred RCT with a recruitment target of 210 subjects (105 in each arm). Children age 3-5 years with symptoms of OSA, are recruited through doctor referral, at the point of referral to the Ear Nose and Throat (ENT) services. Screening is initially with a questionnaire (Paediatric Sleep Questionnaire, PSQ) for symptoms of obstructive sleep apnoea (OSA). Where questionnaires are positive (suggestive of OSA) and ENT surgeons recommend them for adenotonsillectomy, they are invited to participate in POSTA. Baseline testing includes neurocognitive testing (IQ and psychometric evaluation with the neuropsychologist blinded to randomisation) and overnight polysomnography (PSG). Where the Obstructive Apnoea-Hypopnea Index (OAHI) from the PSG is <10/h per hour, consent for randomisation is sought; children with severe OSA (OAHI ≥ 10/h) are sent for immediate treatment and excluded from the study. After consent is obtained, participants are randomised to early surgery (within 2 months) or to surgery after a usual wait time of 12 months. Follow-up studies include repeat neurocognitive testing and PSG at 12 (with the waiting list group studied before their surgery) and 24 months after randomisation. Analysis will be by intention to treat. The primary outcome is IQ at 12 months' follow-up. DISCUSSION: If IQ deficits associated with OSA are reversible 12 months after adenotonsillectomy compared to controls, future clinical practice advise would be to undertake early surgery in young children with OSA. The study could provide data on whether a window of opportunity exists for reversing IQ deficits linked to OSA in the pre-school age-group. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registration Number ACTRN12611000021976 .

High-flow nasal oxygen for children's airway surgery to reduce hypoxaemic events: a randomised controlled trial.

BACKGROUND: Tubeless upper airway surgery in children is a complex procedure in which surgeons and anaesthetists share the same operating field. These procedures are often interrupted for rescue oxygen therapy. The efficacy of nasal high-flow oxygen to decrease the frequency of rescue interruptions in children undergoing upper airway surgery is unknown. METHODS: In this multicentre randomised trial conducted in five tertiary hospitals in Australia, children aged 0-16 years who required tubeless upper airway surgery were randomised (1:1) by a web-based randomisation tool to either nasal high-flow oxygen delivery or standard oxygen therapy (oxygen flows of up to 6 L/min). Randomisation was stratified by site and age (<1 year, 1-4 years, and 5-16 years). Subsequent tubeless upper airway surgery procedures in the same child could be included if there were more than 2 weeks between the procedures, and repeat surgical procedures meeting this condition were considered to be independent events. The oxygen therapy could not be masked, but the investigators remained blinded until outcome data were locked. The primary outcome was successful anaesthesia without interruption of the surgical procedure for rescue oxygenation. A rescue oxygenation event was defined as an interruption of the surgical procedure to deliver positive pressure ventilation using either bag mask technique, insertion of an endotracheal tube, or laryngeal mask to improve oxygenation. There were ten secondary outcomes, including the proportion of procedures with a hypoxaemic event (SpO2 <90%). Analyses were done on an intention-to-treat (ITT) basis. Safety was assessed in all enrolled participants. This trial is registered in the Australian New Zealand Clinical Trials Registry, ACTRN12618000949280, and is completed. FINDINGS: From Sept 4, 2018, to April 12, 2021, 581 procedures in 487 children were randomly assigned to high-flow oxygen (297 procedures) or standard care (284 procedures); after exclusions, 528 procedures (267 assigned to high-flow oxygen and 261 assigned to standard care) in 483 children (293 male and 190 female) were included in the ITT analysis. The primary outcome of successful anaesthesia without interruption for tubeless airway surgery was achieved in 236 (88%) of 267 procedures on high-flow oxygen and in 229 (88%) of 261 procedures on standard care (adjusted risk ratio [RR] 1·02, 95% CI 0·96-1·08, p=0·82). There were 51 (19%) procedures with a hypoxaemic event in the high-flow oxygen group and 57 (22%) in the standard care group (RR 0·86, 95% CI 0·58-1·24). Of the other prespecified secondary outcomes, none showed a significant difference between groups. Adverse events of epistaxis, laryngospasm, bronchospasm, hypoxaemia, bradycardia, cardiac arrest, hypotension, or death were similar in both study groups. INTERPRETATION: Nasal high-flow oxygen during tubeless upper airway surgery did not reduce the proportion of interruptions of the procedures for rescue oxygenation compared with standard care. There were no differences in adverse events between the intervention groups. These results suggest that both approaches, nasal high-flow or standard oxygen, are suitable alternatives to maintain oxygenation in children undergoing upper airway surgery. FUNDING: Thrasher Research Fund, the Australian and New Zealand College of Anaesthetists, the Society for Paediatric Anaesthesia in New Zealand and Australia.

Reciprocal induction of simple organogenesis by mouse kidney progenitor cells in three-dimensional co-culture.

Kidney development is regulated by a coordinated reciprocal induction of metanephric mesenchymal (MM) and ureteric bud (UB) cells. Here, established MM and UB progenitor cell lines were recombined in three-dimensional Matrigel implants in SCID mice. Differentiation potential was examined for changes in phenotype, organization, and the presence of specialized proteins using immunofluorescence and bright-field and electron microscopy. Both cell types, when grown alone, did not develop into specialized structures. When combined, the cells organized into simple organoid structures of polarized epithelia with lumens surrounded by capillary-like structures. Tracker experiments indicated the UB cells formed the tubuloid structures, and the MM cells were the source of the capillary-like cells. The epithelial cells stained positive for pancytokeratin, the junctional complex protein ZO-1, collagen type IV, as well as UB and collecting duct markers, rearranged during transfection (RET), Dolichos biflorus lectin, EndoA cytokeratin, and aquaporin 2. The surrounding cells expressed α-smooth muscle actin, vimentin, platelet endothelial cell adhesion molecule 1 (PECAM), and aquaporin 1, a marker of vasculogenesis. The epithelium exhibited apical vacuoles, microvilli, junctional complexes, and linear basement membranes. Capillary-like structures showed endothelial features with occasional pericytes. UB cell epithelialization was augmented in the presence of MM cell-derived conditioned medium, glial-derived neurotrophic factor (GDNF), hepatocyte growth factor (HGF), or fibronectin. MM cells grown in the presence of UB-derived conditioned medium failed to undergo differentiation. However, UB cell-derived conditioned medium induced MM cell migration. These studies indicate that tubulogenesis and vasculogenesis can be partially recapitulated by recombining individual MM and UB cell lineages, providing a new model system to study organogenesis ex vivo.

Button battery injury: An update.

BACKGROUND: Paediatric button battery injuries present a challenge in the general practice setting. Although some children present with history or parental suspicion of button battery ingestion (BBI) or insertion, unwitnessed cases may present with non-specific symptoms that can mimic many respiratory and gastrointestinal pathologies. OBJECTIVE: The aim of this article is to increase awareness of the fast onset of life-threatening tissue injury from BBI and the importance of timely referral as well as provide an update on current management, including first aid management in the general practice setting. DISCUSSION: BBI is a medical emergency. The button battery requires urgent removal as it can cause caustic burn injury to its surrounding tissues in as little as 15 minutes. Limited awareness of the time-critical nature of this presentation has been reported in multiple triage settings. Studies have shown a role for consumption of honey or sucralfate in delaying tissue injury while awaiting surgical removal.

Management of oesophageal impaction of button batteries in Queensland.

BACKGROUND: Oesophageal button battery impaction (OBBI) is a medical emergency requiring timely removal due to rapid oesophageal tissue injury. The aim of this study was to characterize circumstances of OBBI and identify potential barriers to timely removal of button batteries (BB) in the paediatric population. METHODS: This is a retrospective review of OBBI cases between January 2018 to June 2019. Medical records were used to obtain patient demographics, battery size and type, battery source, location of initial presentation and outcomes. Time to obtaining x-ray, transfer to tertiary centre and to removal of button battery were recorded. RESULTS: Eight cases of OBBI were recorded during the 18 months study timeframe. Six patients were male and two were female, aged 0.97 to 2.8 years. Six were from an English-speaking background and two were from families of non-English speaking background. Battery removal occurred at Queensland Children's Hospital (QCH) in seven of eight cases. Time from ingestion to initial presentation to hospital ranged from 39 min to 123 h with a mean time of 2 h and 13 min. Overall, the total time from ingestion of BB to removal ranged from 2 h 54 min to 126 h 51 min. CONCLUSION: Despite being recognized as a time critical emergency, diagnostic, geographic and logistic challenges in Queensland make optimal care a challenge. Primary prevention strategies coupled with an expanded network for safe battery removal, and novel management strategies such as honey and acetic acid could improve care and reduce morbidity.

Airway Microbiology in Tracheostomized Children.

BACKGROUND: Potentially pathogenic microorganisms are frequently isolated from tracheostomized children, although evidence for empirical therapy of respiratory exacerbation is limited. We aimed to describe upper airway microbiology as found on endotracheal aspirate (ETA) in tracheostomized children and to correlate it with lower airway microbiology through bronchoalveolar lavage fluid. METHODS: We retrospectively reviewed records and airway microbiology of all tracheostomized children under the follow-up care of Queensland Children's Hospital. Subanalysis was based on ventilatory and multidrug-resistant organism status. Sensitivity and specificity of ETA for predicting Pseudomonas aeruginosa and Staphylococcus aureus lower airway isolation were calculated using concomitant bronchoalveolar lavage fluid culture as the accepted standard. RESULTS: From 43 children (18 female, median [interquartile range (IQR)] age 68 (41-115) months, 14 ventilated), 15 different potentially pathogenic microorganisms were isolated (mean ± SD: 3.30 ± 2.23), with S. aureus (n = 33, 77%) and P. aeruginosa (n = 29, 67%) predominating. Significantly more types of potentially pathogenic microorganisms were isolated from ventilated children (median 4.00 [IQR 3.25-5.75]) than from nonventilated children (median 2.00 [IQR 1.00-4.00] (P = .007), with 93% of ventilated children isolating S. aureus and 86% P. aeruginosa. Multidrug-resistant organisms were present in 12 (28%) children, of whom 8 were ventilated. Methicillin-resistant S. aureus (MRSA) was isolated in 9 (21%) children, of whom 6 were ventilated. For P. aeruginosa and S. aureus isolation, ETA had high sensitivity (95% and 100%, respectively) but low specificity (64.7% and 33.3%, respectively) when compared with bronchoalveolar lavage fluid. CONCLUSIONS: In children with tracheostomy, the predominant respiratory bacterial pathogens were S. aureus and P. aeruginosa, with MRSA being isolated less frequently than previously described. Multidrug-resistant organisms are isolated more frequently from ventilated children. ETA microbiology is a good screening modality, with negative ETA potentially ruling out lower airway S. aureus and P. aeruginosa. Adequately powered prospective studies with quantitative cultures could enhance understanding and guide therapy.

Treatment of Mental Illness Prior to Suicide: A National Investigation of 12,909 patients, 2001-2016.

OBJECTIVE: Previous research suggests that up to 90% of individuals who die by suicide may have a mental disorder at the time of death but that levels of treatment may be low. This study aimed to examine undertreatment among patients with mental health conditions who died by suicide and to assess the association between patients' clinical and sociodemographic characteristics and treatment receipt. METHODS: The study's sample included 12,909 patients in England and Wales who died by suicide within 12 months of contact with mental health services between 2001 and 2016. All patients had received a diagnosis of bipolar affective disorder, schizophrenia, depression, or an anxiety disorder. Records of patients who were not receiving treatment as recommended by national clinical guidelines at the time of death were examined for levels of nonprescription of treatment and nonadherence. RESULTS: Twenty-four percent of the patients did not receive treatment, 11% had not been prescribed treatment, and 13% were nonadherent with treatment. These proportions differed by diagnosis. After adjustment for main primary diagnosis, analyses showed that being under age 40, unemployment, living alone, drug misuse, medication side effects, and comorbid personality disorder were independently associated with a decreased likelihood of receiving treatment. CONCLUSIONS: One-quarter of patients with mental health conditions who die by suicide may not be receiving relevant interventions at the time of death. Levels of and reasons for nontreatment vary by diagnosis, but measures to address comorbid diagnoses and implement interventions to improve adherence in specific groups could have an impact.

Laryngeal amyloidosis.

PURPOSE OF REVIEW: Laryngeal amyloidosis is a rare hematological disorder of plasma cells. The cause is still considered idiopathic. The otolaryngology literature predominantly comprises case reports and short series. The present review summarizes the amyloid literature more generally in order to assist the otolaryngologist managing this disorder. RECENT FINDINGS: Distinguishing localized amyloidosis from systemic disease continues to be challenging. Both radiological and hematological investigations may assist. Surgery continues to be the predominant modality for treatment, but radiation and potentially medical approaches are on the horizon. SUMMARY: When localized, this benign laryngeal disease carries an excellent prognosis. Clinicians should however be aware of systemic presentations and ensure patients receive long-term follow-up.

Paediatric inhaled airway foreign bodies: An update.

BACKGROUND: Given the often subacute nature of airway foreign bodies (AFB), which may have no or limited symptoms, patients with AFB sometimes present to general practitioners (GPs). It is important that AFB are promptly recognised and referred for appropriate tertiary management. OBJECTIVE: The aim of this paper is to outline how AFB may present in the general practice setting and review the appropriate clinical work-up and tertiary referral. It also outlines the role of GPs in education of parents and caregivers of young children. DISCUSSION: Paediatric patients with AFB can be asymptomatic or have vague pulmonary or upper airway symptoms after a choking episode when they present to the GP. It is important that historical red flags that mandate immediate specialist review are recognised, even in the otherwise asymptomatic child. Delays in diagnosis can result in severe and occasionally lifelong pulmonary complications with significant morbidity. GPs develop important long-term relationships with parents and caregivers of young children, which makes them uniquely positioned to provide potentially life-saving education regarding both the prevention and acute management of AFB.

High-flow oxygen for children's airway surgery: randomised controlled trial protocol (HAMSTER).

INTRODUCTION: Hypoxaemia during anaesthesia for tubeless upper airway surgery in children with abnormal airways is common due to the complexity of balancing adequate depth of anaesthesia with maintenance of spontaneous breathing and providing an uninterrupted field of view of the upper airway for the surgeon. High-flow nasal oxygenation (HIGH-FLOW) can prolong safe apnoea time and be used in children with abnormal airways but to date has not been compared with the alternative technique of low-flow nasal oxygenation (LOW-FLOW). The aim is to investigate if use of HIGH-FLOW can reduce the number of hypoxaemic events requiring rescue oxygenation compared with LOW-FLOW. METHODS AND ANALYSIS: High-flow oxygen for children's airway surgery: randomised controlled trial (HAMSTER) is a multicentre, unmasked, randomised controlled, parallel group, superiority trial comparing two oxygenation techniques during anaesthesia. Children (n=530) aged >37 weeks to 16 years presenting for elective tubeless upper airway surgery who fulfil inclusion but not exclusion criteria will be randomised prior to surgery to HIGH-FLOW or LOW-FLOW post induction of anaesthesia. Maintenance of anaesthesia with HIGH-FLOW requires Total IntraVenous Anaesthesia (TIVA) and with LOW-FLOW, either inhalational or TIVA at discretion of anaesthetist. The primary outcome is the incidence of hypoxaemic events requiring interruption of procedure for rescue oxygenation by positive pressure ventilation and the secondary outcome includes total hypoxaemia time, adverse cardiorespiratory events and unexpected paediatric intensive care admission admission. Hypoxaemia is defined as Sp02 <90%. Analysis will be conducted on an intention-to-treat basis. ETHICS AND DISSEMINATION: Ethical approval has been obtained by Children's Health Queensland Human Research Ethics Committee (HREC/18/QRCH/130). The trial commenced recruitment in 2018. The primary manuscript will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: The HAMSTER is registered with the Australia and New Zealand Clinical TrialsRegistry: ACTRN12618000949280.

Bilateral vocal cord palsy causing stridor as the only symptom of syringomyelia and Chiari I malformation, a case report.

INTRODUCTION: Bilateral vocal cord palsy is a condition which has many causes (Gupta et al., 2012) [1]. Syringomyelia is an uncommon condition which describes the formation of fluid filled cavity, occupying the spinal cord (Chang, 2003) [2]. It rarely manifests itself as subacute onset of stridor. PRESENTATION OF CASE: We present the case of a three year old female who presented for evaluation of her speech and language delay, when incidentally it was made note of her loud breathing which had previously been managed as bronchiolitis by her general practitioner. In hospital she was found to have a bilateral vocal cord palsy. Further investigation revealed a large syrinx as well as an associated Arnold Chiari 1 malformation, for which she required neurosurgical decompression. CONCLUSION: Although uncommon, formation of a syrinx should be considered for patients who present with stridor and reiterates the importance of MRI as an important investigative tool of bilateral vocal cord palsy.