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Competing Interests: Competing interests: None declared.

This retrospective review of 33 children's dynamic 4-dimensional (4-D) computed tomography (CT) images of the airways, performed using volume scanning on a 320-detector array without anaesthesia (free-breathing) and 1.4-s continuous scanning, was undertaken to report technique, pitfalls, quality, radiation doses and findings. Tracheobronchomalacia (airway diameter collapse >28%) was recorded. Age-matched routine chest CT scans and bronchograms acted as benchmarks for comparing effective dose. Pitfalls included failure to administer intravenous contrast, pull back endotracheal tubes and/or remove nasogastric tubes. Twenty-two studies (67%) were diagnostic. Motion artefact was present in 16 (48%). Mean effective dose: dynamic 4-D CT 1.0 mSv; routine CT chest, 1.0 mSv, and bronchograms, 1.4 mSv. Dynamic 4-D CT showed tracheobronchomalacia in 20 patients (61%) and cardiovascular abnormalities in 12 (36%). Fourteen children (70%) with tracheobronchomalacia were managed successfully by optimising conservative management, 5 (25%) underwent surgical interventions and 1 (5%) died from the presenting disorder.

Levodopa-carbidopa intestinal gel (LCIG) is an effective treatment for Parkinson disease. Initiating therapy involves an initial naso-jejunal (NJ) titration phase. The NJ phase is prolonged with significant morbidity. The aim of this study is to assess the impact of proceeding without the NJ phase on resource utilisation and the outcomes of patients. Twenty-five patients were started on LCIG using the patients existing levodopa equivalent dose (LED). We recorded change in LED, length of hospital stay, readmission rates and use of outpatient services and clinical outcomes within 6 months. The median length of stay was 4.5 days. Patients had four outpatient clinic reviews and 2.5 community nurse contacts within 6 months. There was no significant change in daily LED on discharge (P = 0.56). There were significant improvements in all Unified Parkinson Disease Rating Scale subscores (P < 0.05), the Freezing of Gait scale (P < 0.01) and Parkinson Disease Quality Of Life 39 score (P < 0.01). Initiating LCIG without the NJ phase resulted in short admissions, a minimal outpatient burden and no significant requirement for dose titration while producing good clinical outcomes., (© 2018 Royal Australasian College of Physicians.)

Background: Despite the widespread use of the Progressive Supranuclear Palsy Rating Scale (PSPRS), it is not known what change in this scale is meaningful for patients., Methods: We analyzed data from a large clinical trial in PSP-Richardson's syndrome (AL-108-231) to calculate minimal clinically important worsening. This was defined as the difference in mean change of PSPRS in subjects rated "a little worse" and those rated "unchanged" on the Clinicians' Global Impression of Change Scale. A multivariate analysis using logistic regression assessed the relationship between clinical worsening, PSPRS, depression, and activities of daily living., Results: The minimal clinically important worsening on the PSPRS was 5.7 points, corresponding to the mean decline over 6 months in the trial. Changes in activities of daily living and PSPRS were significantly associated with clinical worsening., Conclusions: Clinically meaningful change is measurable on the PSPRS over 6 months. © 2016 International Parkinson and Movement Disorder Society., (© 2016 2016 International Parkinson and Movement Disorder Society.)

Cerebro-Costo-Mandibular syndrome (CCMS) is a rare autosomal dominant condition comprising branchial arch-derivative malformations with striking rib-gaps. Affected patients often have respiratory difficulties, associated with upper airway obstruction, reduced thoracic capacity, and scoliosis. We describe a series of 12 sporadic and 4 familial patients including 13 infants/children and 3 adults. Severe micrognathia and reduced numbers of ribs with gaps are consistent findings. Cleft palate, feeding difficulties, respiratory distress, tracheostomy requirement, and scoliosis are common. Additional malformations such as horseshoe kidney, hypospadias, and septal heart defect may occur. Microcephaly and significant developmental delay are present in a small minority of patients. Key radiological findings are of a narrow thorax, multiple posterior rib gaps and abnormal costo-transverse articulation. A novel finding in 2 patients is bilateral accessory ossicles arising from the hyoid bone. Recently, specific mutations in SNRPB, which encodes components of the major spliceosome, have been found to cause CCMS. These mutations cluster in an alternatively spliced regulatory exon and result in altered SNRPB expression. DNA was available from 14 patients and SNRPB mutations were identified in 12 (4 previously reported). Eleven had recurrent mutations previously described in patients with CCMS and one had a novel mutation in the alternative exon. These results confirm the specificity of SNRPB mutations in CCMS and provide further evidence for the role of spliceosomal proteins in craniofacial and thoracic development., (© 2016 Wiley Periodicals, Inc.)

The role of vitamin D supplementation in preventing multiple sclerosis (MS) and/or treating MS progression is an area of significant research interest. We detail the current status of the ongoing research in this field, and note the lack of class 1 evidence from well-conducted, large, double-blind, placebo-controlled studies of vitamin D supplementation in the prevention and/or treatment of MS. We have been able to provide some guidelines for practitioners based on the substantial burden of supportive evidence for the use of vitamin D in MS as summarised here. These guidelines may provide some support to those clinicians who treat people with MS and their families., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

We examine the incidence and prevalence of domiciliary ventilation in the South West region of the UK, assess trends over 15 years, and describe patient outcome. We conducted a retrospective review of all patients below 18 years receiving domiciliary ventilation in the South West region of the UK between January 1994 and August 2009. Children who received long-term ventilation solely in hospital were excluded from the study. Information was obtained from a locally held database, medical notes, and hospital administration systems. One hundred-six patients were identified. Prevalence has increased since 1994 from 0.2 to 6.7 per 100,000 children. The incidence of both invasive and non-invasive ventilations has increased with a trend towards more non-invasive therapy. The commonest underlying disorders were airway pathology (37 patients), neuromuscular disease (34 patients), and central congenital hypoventilation disorder (17 patients). Sixty-seven patients had significant co-morbidities. Of 38 non-current patients, 19 were transferred to adult ventilation services, 11 died, and 6 were successfully weaned from ventilatory support. In conclusion, there has been a 30-fold increase in the prevalence of paediatric domiciliary ventilation, in the South West region of the UK, since 1994. Co-morbidities are common. Very few children discontinue long-term ventilation, and increasing numbers of ventilated children are transferred to adult services.

Unlabelled: Children with Down syndrome (DS) are at greater risk of pulmonary arterial hypertension (PAH) than the general population, partly due to upper airway obstruction and congenital heart disease. We wished to review our management of PAH and suggest a protocol for the systematic management of these children. Children with DS and PAH were included as referred for assessment from March 2005 to May 2010. Twenty-five patients (13 boys) met inclusion criteria. The median age was 385 days (range, 106 to 5,734); mean tricuspid regurgitation jet was 3.5 (range, 2.7-4.8) m/s. At cardiac catheterisation, mean pulmonary artery mean pressure was 26 mmHg (range, 12 to 46), and mean pulmonary vascular resistance (PVR) was 4.14 U.m² (range, 1.20 to 12.43) at baseline. PVR fell to a mean of 2.68 U.m² (range, 0.38 to 10.69) with 20 ppm inhaled nitric oxide and 100% oxygen. Respiratory assessment included polysomnography (18), bronchoscopy (16), showing malacia (eight), adenotonsillar hypertrophy (eight) and floppy aryepiglottic folds (four). One lung biopsy showed plexogenic arteriopathy, and one was diagnosed with tracheo-oesophageal fistula., Conclusion: In order to manage this complex group of patients, a combined cardiological, respiratory and surgical approach was required. A protocol with cardiac catheterisation, blood tests and respiratory assessment is suggested for the management of pulmonary hypertension in these children.

Background: Patients with complex congenital heart disease associated with tracheobronchomalacia (TBM) remain difficult to manage after cardiac surgery. We studied the influence of TBM on the outcomes of pediatric patients after cardiac surgery for congenital heart disease to determine how to manage these patients better., Methods: Twenty-two consecutive pediatric patients who had TBM diagnosed by bronchoscopy or dynamic contrast bronchography before or after cardiac surgery for congenital heart disease during a 5.5-year period were compared with an age- and procedure-matched control group operated on during the same period. Patients diagnosed postoperatively were investigated after a second failed extubation. Patients were managed by oxygen administration, endotracheal suctioning, and positive end-expiratory or continuous positive airway pressure through a nasotracheal tube or tracheostomy., Results: There were 4 deaths within 1 year of surgery, all in the study group, with 2 early (neither of which appeared related to TBM) and 2 late. The estimated survival at 5 years was 82% (95% confidence interval, 59% to 93%) for the study group compared with 100% for control patients (p = 0.012). All deaths occurred in patients undergoing palliative procedures (p = 0.0004), and both children who underwent redo operations died (p = 0.02). Postoperatively, 50% of children with TBM required prolonged ventilation and tracheostomy. Compared with control patients the average postoperative ventilation time, pediatric intensive care unit stay, and hospital stay were 6.5, 11.5, and 20 days versus 1, 2, and 6.5 days, respectively (p < 0.001)., Conclusions: Although associated with longer postoperative ventilation time, pediatric intensive care unit stay, hospital stay, and mortality, outcomes after cardiac procedures in children with TBM are acceptable. Palliative and redo procedures in this group of patients are associated with significantly higher risk of death.

Alterations to pulmonary surfactant structure, composition, and function contribute to the severity of respiratory infections. Analysis of bronchoalveolar lavage fluid (BALF) from children undergoing diagnostic bronchoscopy for structural abnormalities (control group, n = 24), asthma (n = 18), lung infection (n = 30), and cystic fibrosis (CF, n = 15) showed that BALF phospholipid concentration decreased with age for the control group and was elevated in all disease groups. The fractional concentration of the major surface active component, dipalmitoyl phosphatidylcholine (PC16:0/16:0), correlated (r(2) = 0.608, P < 0.01) with airway resistance (FEV(1%) predicted), and decreased PC16:0/16:0 was accompanied by increased concentrations of phospholipid components characteristic of cell membranes (PC16:0/18:1 and PI18:0/20:4). Median minimal surface tension, measured by pulsating bubble surfactometer, was elevated (P < 0.01) in both infection (17.5 mN/m) and CF (17.1 mN/m) compared with the control group (1.5 mN/m). Centrifugation (60,000 x g, 40 min) of BALF indicated that infection was accompanied by accumulation of large aggregate forms of surfactant, in contrast to previous reports of increased conversion to inactive small aggregate surfactant particles in ventilated patients with respiratory failure. This accumulation of surface-inactive, large aggregate forms of surfactant, possibly due to mixing with membrane material from inflammatory cells, may contribute to severity of lung disease in children with respiratory infections.

Chronic aspiration is a cause of life-threatening respiratory complications and repeated hospital admissions, particularly in children with neurological disabilities. Determining the source of aspiration is important for optimizing treatment. This report describes a simple technique to demonstrate salivary aspiration during fibreoptic bronchoscopy. A child with a history of recurrent pneumonia was given methylene blue orally 2 h prior to fibreoptic bronchoscopy. Bronchoscopy was carried out through a laryngeal mask airway under inhalational anaesthesia. The stained saliva was seen to be pooling in the valleculae and then running down the trachea into the bronchi, confirming salivary aspiration.

Ninety-eight children aged 1-15 years entered a randomized double-blind study investigating an appropriate dose of oral prednisolone in children admitted to hospital with an acute exacerbation of asthma. None of the children had recently been treated with oral prednisolone. Following admission, the children were randomized to receive prednisolone 0.5 mg kg-1, 1.0 mg kg-1 or 2.0 mg kg-1 in a single daily dose in addition to nebulized bronchodilators. Clinical asthma scores, oxygen saturations, pulse rate, duration of admission and number of nebulizers given were compared in the three treatment groups. Thirty-five children received 0.5 mg kg-1, 33 received 1.0 mg kg-1 and 30 received 2.0 mg kg-1. There were no significant differences in the pattern of recovery between the three treatment groups. There were no advantages in using higher doses of prednisolone. We recommend 0.5 mg kg-1 day-1 of prednisolone as an appropriate dose for treating an acute exacerbation of asthma.

Twenty-four children aged 12-17 years entered a randomized, double-blind placebo-controlled study investigating the use of salmeterol in chronic severe asthma. In addition to their usual medication, the children were given either placebo or 100 micrograms salmeterol b.d. by dry powder inhalation. Treatment was continued throughout one term at a residential school for asthma. Symptom scores, peak expiratory flow rates, spirometry and quality-of-life scores were compared between the two treatment groups. One child withdrew during the run-in period. Twelve pupils received placebo and 11 pupils received salmeterol. There were consistent improvements in favour of salmeterol, reaching statistical significance for morning and evening peak flow rates and spirometry when measured on four occasions during the study period. There were no medication-related adverse events recorded and no pulse rate changes. Salmeterol (100 micrograms b.d.) is well tolerated and efficacious in older children with chronic severe asthma.

Both song behavior and its neural substrate are hormone sensitive: castrated adult male zebra finches need replacement of gonadal steroids in order to restore normal levels of song production, and sex steroids are necessary to establish male-typical neural song-control circuits during early development. This pattern of results suggests that hormones may be required for normal development of learned song behavior, but evidence that steroids are necessary for normal neural and behavioral development during song learning has been lacking. We addressed this question by attempting to eliminate the effects of gonadal steroids in juvenile male zebra finches between the time of initial song production and adulthood. Males were castrated at 20 days of age and received systemic implants of either an antiandrogen (flutamide), an antiestrogen (tamoxifen), or both drugs. The songs of both flutamide- and tamoxifen-treated birds were extremely disrupted relative to normal controls in terms of the stereotypy and acoustic quality of individual note production, as well as stereotypy of the temporal structure of the song phrase. We did not discern any differences in the pattern of behavioral disruption between birds that were treated with either flutamide, tamoxifen, or a combination of both drugs. Flutamide treatment resulted in a reduced size of two forebrain nuclei that are known to play some role unique to early phases of song learning [lateral magnocellular nucleus of the anterior neostriatum (IMAN) and area X (X)], but did not affect the size of two song-control nuclei that are necessary for normal song production in adult birds [caudal nucleus of the ventral hyperstriatum (HVc) and robust nucleus of the archistriatum (RA)]. In contrast, treatment with tamoxifen did not result in any changes in the size of song-control nuclei relative to normal controls, and it blocked the effects of flutamide on the neural song-control system in birds that were treated with both drugs. Castration and antisteroid treatment exerted no deleterious effects on the quality of song behavior in adult birds, indicating that gonadal hormones are necessary for the development of normal song behavior during a sensitive period.