Interstitial lung disease and pancreatic exocrine insufficiency in CADDS: Phenotypic expansion and literature review.

Contiguous ABCD1/ DXS1357E deletion syndrome (CADDS) is a rare deletion syndrome involving two contiguous genes on Xq28, ABCD1 and BCAP31 (formerly known as DXS1357E). Only nine individuals with this diagnosis have been reported in the medical literature to date. Intragenic loss-of-function variants in BCAP31 cause the deafness, dystonia, and cerebral hypomyelination syndrome (DDCH). Isolated pathogenic intragenic variants in ABCD1 are associated with the most common peroxisomal disorder, X-linked adrenoleukodystrophy (X-ALD), a single transporter deficiency, which in its more severe cerebral form is characterised by childhood-onset neurodegeneration and high levels of very-long-chain fatty acids (VLCFA). While increased VLCFA levels also feature in CADDS, the few patients described to date all presented as neonates with a severe phenotype. Here we report a tenth individual with CADDS, a male infant with dysmorphic facial features who was diagnosed through ultra-rapid whole genome sequencing (WGS) in the setting of persistent cholestatic liver disease, sensorineural hearing loss, hypotonia and growth failure and developmental delay. Biochemical studies showed elevated VLCFA and mildly reduced plasmalogens. He died at 7 months having developed pancreatic exocrine deficiency and interstitial lung disease, two features we propose to be possible extensions to the CADDS phenotype. We also review the genetic, phenotypic, and biochemical features in previously reported individuals with CADDS.

Assessing sleep in children with Down syndrome: Comparison of parental sleep diaries, actigraphy and polysomnography.

BACKGROUND: This study compared measurements of sleep and wake assessed with actigraphy, sleep diary and polysomnography in children with Down syndrome (DS) and also compared measures of actigraphic sleep recording in children with DS and typically developing (TD) children. METHODS: Children with DS aged 3-19 years (N = 44) referred for assessment of sleep disordered breathing (SDB) underwent overnight polysomnography, together with 1 week of actigraphy with sleep diary. Actigraphy data from the children with DS were compared with data collected from TD children, matched for age and sex. RESULTS: 22 children (50%) with DS completed >3 consecutive nights of actigraphy with a matched sleep diary. There were no differences between bedtimes, wake times or time in bed on weeknights, weekends or over 7 nights between actigraphy and sleep diary. Total sleep time was over estimated by the sleep diary by almost 2 h and the number of night awakenings under-reported. Compared to matched TD children (N = 22), there was no difference in total sleep time, however children with DS fell asleep more quickly (p < 0.001), had more awakenings (p = 0.001) and more time awake after sleep onset (p = 0.007). Children with DS exhibited less variability in both bedtimes and wake times, and fewer had >1 h sleep schedule variability. CONCLUSIONS: Parental sleep diaries over-estimate total sleep time but accurately report bed and wake times compared to actigraphy in children with DS. Children with DS have more regular sleep patterns than TD children of the same age, which is important for optimising daytime functioning. The reasons behind this warrant further investigation.

Demonstration of Accuracy and Feasibility of Remotely Delivered Oximetry: A Blinded, Controlled, Real-World Study of Regional/Rural Children with Obstructive Sleep Apnoea.

Objectives: Evaluate diagnostic accuracy and feasibility of a mail-out home oximetry kit. Design: Patients were referred for both the tertiary/quaternary-centre hospital-delivered oximetry (HDO) and for the mail-out remotely-delivered oximetry (RDO). Quantitative and qualitative data were collected. The COVID-19 pandemic began during this study; therefore, necessary methodological adjustments were implemented. Setting: Patients were first evaluated in Swan Hill, Victoria. RDO kits were sent to home addresses. For the HDO, patients travelled to the Melbourne city area, received the kit, stayed overnight, and returned the kit the following morning. Participants: All consecutive paediatric patients (aged 2−18), diagnosed by a specialist in Swan Hill with obstructive sleep apnoea (OSA) on history/examination, and booked for tonsillectomy +/− adenoidectomy, were recruited. Main outcome measures: Diagnostic accuracy (i.e., comparison of RDO to HDO results) and test delivery time (i.e., days from consent signature to oximetry delivery) were recorded. Patient travel distances for HDO collection were calculated using home/delivery address postcodes and Google® Maps data. Qualitative data were collected with two digital follow-up surveys. Results: All 32 patients that had both the HDO and RDO had identical oximetry results. The HDO mean delivery time was 87.7 days, while the RDO mean delivery time was 23.6 days (p value: <0.001). Qualitatively, 3/28 preferred the HDO, while 25/28 preferred the RDO (n = 28). Conclusions: The remote option is as accurate as the hospital option, strongly preferred by patients, more rapidly completed, and also an ideal investigation delivery method during certain emergencies, such as the COVID-19 pandemic.

Perioperative Care of Children with Severe Neurological Impairment and Neuromuscular Scoliosis-A Practical Pathway to Optimize Peri-Operative Health and Guide Decision Making.

Neuromuscular scoliosis is a common feature in children with severe neurological impairment (SNI), including those with severe cerebral palsy. Surgical correction of scoliosis is the mainstay of treatment. This group of patients also have associated medical complexity. The complication rates post-surgery are high, although, for many, they are worth the risk. There are currently no published practice guidelines or care pathways for children with SNI who are undergoing scoliosis corrective surgery. In response to the high uptake of this surgery, coupled with the expected complication rates, our hospital established a perioperative clinic. The purpose of this paper is to describe our perioperative approach. This clinic has developed into a service beyond perioperative care and, with the collaborative meeting, enables shared decision-making to identify the right candidate for surgery. The process involves surgical expertise, understanding the family and child at the centre, and optimisation of medical care pre- and post-surgery. In this paper, we describe the process in a step-by-step manner. We provide clinical vignettes, as well as the proformas that we use, and we highlight the benefits of the team-based process.

Persistent pleuritic chest pain in a patient with cystic fibrosis.

Pleural effusion is rare in cystic fibrosis. Infection leading to pleural effusion is likely to be polymicrobial, including contributory fungal infection; microbiology of pleural fluid is commonly discordant with sputum. https://bit.ly/3MJXrhk.

Delivering multidisciplinary neuromuscular care for children via telehealth.

INTRODUCTION/AIMS: In response to coronavirus disease 2019 (COVID-19) pandemic restrictions int 2020, our face-to-face (F2F) multidisciplinary neuromuscular clinic (NMC) transitioned to widespread use of telehealth (TH). This study aimed to (1) understand parent/guardian, child, and clinician perceptions of TH; (2) examine TH-related changes in clinical activity; and (3) use these findings to inform a future model of care for the NMC. METHODS: A clinical audit was undertaken to examine clinical activity throughout 2018-2020. Online surveys were distributed to clinicians and parents of children attending the NMC via TH in 2020. A working group of clinicians created a checklist to guide a future hybrid model of TH and F2F care. RESULTS: Total clinical activity in 2020 was maintained from previous years; 62.8% of all appointments occurred via TH, and 82.3% of patients attended NMC by TH at least once. Ninety-nine parents (30.6% response rate), 52 children, and 17 clinicians (77% response rate) responded to the survey. All groups reported better interaction when F2F compared to TH. Eighty percent of parents identified advantages of TH and reported lower levels of stress. A lack of "hands-on" physical assessment was identified by parents and clinicians as a TH limitation. Most families (68.1% of parents; 58.8% of children) and all clinicians indicated a preference for a mix of TH and F2F NMC appointments in the future. DISCUSSION: This study has informed a checklist to guide future TH use in a new hybrid model of care. Further investigation is required to assess health impacts of TH use in pediatric neuromuscular care.

Is cardiorespiratory disease associated with increased susceptibility of SARS-CoV-2 in children?

BACKGROUND: There are limited data in pediatric populations evaluating whether chronic cardiorespiratory conditions are associated with increased risk of coronavirus disease 2019 (COVID-19). We aimed to compare the rates of chronic cardiac and respiratory disease in children testing positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2[+]) compared with those testing negative (SARS-CoV-2[-]) at our institution. METHOD: Prospective cohort with nested case-control study of all children tested by polymerase chain reaction (PCR) for SARS-CoV-2 by nasopharyngeal/oropharyngeal sampling between March and October 2020. Children were identified prospectively via laboratory notification with age and sex-matching of SARS-CoV-2[+] to SARS-CoV-2[-] (1:2). Clinical data were extracted from the electronic medical record. RESULTS: In total, 179 SARS-CoV-2[+] children (44% females, median age 3.5 years, range: 0.1-19.0 years) were matched to 391 SARS-CoV-2[-] children (42% female, median age 3.7 years, range: 0.1-18.3 years). The commonest comorbidities showed similar frequencies in the SARS-CoV-2[+] and [-] groups: asthma (n = 9, 5% vs. n = 17, 4.4%, p = 0.71), congenital heart disease (n = 6, 3.4% vs. n = 7, 1.8%, p = 0.25) and obstructive sleep apnoea (n = 4, 2.2% vs. n = 10, 2.3%, p = 0.82). In the SARS-CoV-2[+] group, the prevalence of symptomatic disease was similar among children with and without cardiorespiratory comorbidities (n = 12, 75% vs. n = 103, 57%, p = 0.35). A high proportion of children hospitalized with SARS-CoV-2 infection had cardiac comorbidities (23.8%). CONCLUSIONS: In this single site data set, rates of pre-existing cardiorespiratory disease were similar in SARS-CoV-2[+] and SARS-CoV-2[-] children. Rates of symptomatic infection were similar between children with and without cardiorespiratory comorbidity. High rates of comorbid cardiac disease were observed among hospitalized children with COVID-19 warranting further research to inform vaccine prioritization.

Ventilatory support at home for children: A joint position paper from the Thoracic Society of Australia and New Zealand/Australasian Sleep Association.

The goal of this position paper on ventilatory support at home for children is to provide expert consensus from Australia and New Zealand on optimal care for children requiring ventilatory support at home, both non-invasive and invasive. It was compiled by members of the Thoracic Society of Australia and New Zealand (TSANZ) and the Australasian Sleep Association (ASA). This document provides recommendations to support the development of improved services for Australian and New Zealand children who require long-term ventilatory support. Issues relevant to providers of equipment and areas of research need are highlighted.

Quality of life and mood in children with cystic fibrosis: Associations with sleep quality.

BACKGROUND: We aimed to investigate the relationship between sleep quality, mood and health-related quality of life (HRQOL) in children with CF and controls. METHODS: Children (7-12years) and adolescents (13-18years) with CF and controls completed sleep evaluation: overnight oximetry and 14days of actigraphy. Age-appropriate questionnaires assessed mood (Children's Depression Inventory; CDI or Beck's Depression Inventory), HRQOL (CF Questionnaire-Revised; CFQ-R or PedsQL), and sleepiness (Pediatric Daytime Sleepiness Scale). RESULTS: 87 CF and 55 controls recruited. Children with CF had poorer sleep quality, more sleepiness and lower mood than controls, with a negative correlation between mood score and sleep efficiency. Sleepiness score was predictive of mood score and multiple CFQ-R domains. Adolescents with CF also demonstrated poorer sleep and more sleepiness than controls, but no difference in mood. Reduced sleep quality predicted lower CFQ-R scores. No correlation between sleep, mood or HRQOL in controls. CONCLUSIONS: In children and adolescents with CF, impaired sleep quality is associated with lower mood and HRQOL in an age-specific manner. Future research will aid understanding of effective strategies for prevention and treatment of mood disorders and sleep disturbance in children with CF.

What keeps children with cystic fibrosis awake at night?

BACKGROUND: Sleep disturbance is common in children with cystic fibrosis (CF) however there are limited studies investigating the causes for poor sleep quality. In a cross sectional observational study we aimed to evaluate the clinical correlates of sleep disturbance in this population. METHODS: Children with CF (7-18years) free from pulmonary exacerbation completed medical review, overnight oximetry, the OSA-18 and 14days of actigraphy recordings with a sleep diary. RESULTS: In addition to FEV1 <80% and low baseline SpO2, CF-related diabetes, PEG feeding and co-morbid behaviour disorder were associated with lower objective sleep quantity. Paternal smoking and a family member with a mood disorder were also associated with sleep disturbance. The use of electronic devices before bedtime was associated with lower sleep quantity and quality. FEV1, nocturnal cough, age and a behaviour disorder predicted sleep duration. FEV1, nocturnal cough, SpO2 nadir and asthma predicted sleep efficiency. Conversely, sleep efficiency independently predicted FEV1. CONCLUSIONS: Reduced sleep quality in children with CF is related to lung health and co-morbidities. However, family characteristics and poor sleep hygiene in the child were also associated with sleep disturbance. Optimal management of CF would seem to be the primary intervention to alleviate children's sleep disturbance, however our data raises additional targets for attempts to improve sleep.

Autotitrating CPAP as a Tool for CPAP Initiation for Children.

STUDY OBJECTIVES: Few studies have assessed autotitrating positive airway pressure (autoPAP) for treatment of obstructive sleep apnea (OSA) in children. We aimed to review our use of autoPAP for initiation of continuous positive airway pressure (CPAP) therapy in children, and compare autoPAP-derived treatment pressures to CPAP treatment pressure determined by attended polysomnography (PSG). METHODS: Retrospective review of children initiated on autoPAP from 2013 to 2015. Mean autoPAP pressure (AutoMean pressure) and average device pressure ≤ 90% of time (Auto90 pressure) were taken from downloaded data and compared to the recommended treatment pressure following titration PSG (PSG pressure). RESULTS: Fifty-two children started CPAP, of whom 26 (age ± standard deviation 11.9 ± 3.4 years) used autoPAP and had titration PSG. AutoPAP was used on average 84% of nights (standard deviation 20%) in the first month, with a mean ± standard deviation 6.3 ± 2.0 hours of use on nights used. The median (interquartile range) obstructive apnea-hypopnea index decreased from 16.6 (11, 35) events/h before treatment to 2.2 (0.4, 3.8) events/h on the titration PSG. Median (interquartile range) PSG pressure was 9.0 cm H2O (7.0, 10.0), AutoMean pressure was 6.3 cm H2O (5.3, 7.5), and Auto90 pressure was 8.1 cm H2O (7.1, 9.5). These were significantly different (P < .001), with the significant difference lying between AutoMean and the other two pressures. PSG pressure was greater than or equal to the AutoMean pressure in all cases, and greater than or equal to the Auto90 pressure in 20 out of 26 cases (77%). CONCLUSIONS: AutoPAP is a safe and effective means of initiating CPAP in children. AutoMean and Auto90 pressures are usually below treatment pressure determined by titration PSG.

How Well Do Children with Cystic Fibrosis Sleep? An Actigraphic and Questionnaire-Based Study.

OBJECTIVE: To measure sleep patterns and quality, objectively and subjectively, in clinically stable children with cystic fibrosis (CF) and healthy control children, and to examine the relationship between sleep quality and disease severity. STUDY DESIGN: Clinically stable children with CF and healthy control children (7-18 years of age) were recruited. Sleep patterns and quality were measured at home with actigraphy (14 days). Overnight peripheral capillary oxygen saturation was measured via the use of pulse oximetry. Daytime sleepiness was evaluated by the Pediatric Daytime Sleepiness Scale (PDSS) and subjective sleep quality by the Sleep Disturbance Scale for Children and Obstructive Sleep Apnea-18. RESULTS: A total of 87 children with CF and 55 control children were recruited with no differences in age or sex. Children with CF had significantly lower total sleep time and sleep efficiency than control children due to frequent awakenings and more wake after sleep onset. In children with CF, forced expiratory volume in 1 second and overnight peripheral capillary oxygen saturation nadir correlated positively with total sleep time and sleep efficiency and negatively with frequency of awakenings and wake after sleep onset. Patients with CF had significantly greater Sleep Disturbance Scale for Children (45 vs 35; P < .001), Obstructive Sleep Apnea-18 (35 vs 24; P < .001), and PDSS scores (14 vs 11; P < .001). There was a negative correlation between PDSS and forced expiratory volume in 1 second (r = -0.23; P < .05). CONCLUSIONS: Even in periods of clinical stability, children with CF get less sleep than their peers due to more time in wakefulness during the night rather than less time spent in bed. Objective measures of sleep disturbance and subjective daytime sleepiness were related to disease severity. In contrast, parents of children with CF report high levels of sleep disturbance unrelated to disease severity.

Gastrostomy in children with cystic fibrosis and portal hypertension.

Children with cystic fibrosis-associated liver disease (CFALD) and portal hypertension may require supplemental feeding with gastrostomy; however, this could lead to the development of stomal varices. We assessed this risk and nutritional and pulmonary outcome in a series of 7 children with CFALD and portal hypertension. In 35.1 patient-years of follow-up, none developed stomal varices or had a gastrointestinal bleed attributable to a varix. There was significant improvement in nutrition and lung function 2 years postinsertion. We conclude that gastrostomy placement for poor nutrition in children with CFALD and portal hypertension is safe and contributes to improved nutritional and pulmonary outcome.

Are sleep studies helpful in children with Prader-Willi syndrome prior to commencement of growth hormone therapy?

AIMS: To examine sleep study findings in children with Prader-Willi syndrome (PWS) referred for polysomnography (PSG) before commencement of growth hormone (GH) and to evaluate the impact of sleep testing on treatment decisions. METHODS: The sleep unit database was used to identify all cases over an 8-year period (2003-2011). Standard overnight PSG was performed in the sleep laboratory. Obstructive sleep apnoea (OSA) was defined by an obstructive apnoea-hypopnoea index >1/h. Age, symptoms of OSA, tonsillar size and body mass index (BMI) Z-score were obtained through chart review. RESULTS: OSA was diagnosed in 15 of 34 (44%) cases identified. Those with OSA were significantly older (P = 0.009) and more likely to have enlarged tonsils (P = 0.05) than those without OSA. There was no difference in BMI Z-score or the presence of symptoms of OSA. GH was deferred in 13 (38%) pending treatment for OSA. CONCLUSIONS: OSA was frequently present in children with PWS referred simply to meet the requirement for PSG before starting GH. OSA was more likely in older children and those with enlarged tonsils. GH treatment was deferred in 38% of cases. This study supports routine performance of PSG prior to GH, regardless of clinical history.

Confidentiality with adolescents in the medical setting: what do parents think?

PURPOSE: When confidential health care is provided to adolescents they are more likely to seek care, disclose sensitive information, and return for future visits. Guidelines for health professionals recommend seeing young people alone to facilitate confidential care. We sought to document parental views regarding confidentiality with adolescents, aiming to identify topics that parents believe they should be informed about despite an assurance of confidentiality between their child and the doctor. We also aimed to document harms and benefits that parents associate with adolescents seeing doctors alone. METHODS: A sample of 86 parents attending an adolescent medicine clinic with their son/daughter was surveyed using a brief, anonymous questionnaire. RESULTS: Parents identified several benefits associated with confidential care, yet also believed they should be informed about a wide range of topics, even if their children did not want them to know. Parents' primary concern about confidentiality was a fear of not being informed about important information. CONCLUSIONS: Parental views concerning confidentiality are complex and conflicting and differ from current guidance provided to health professionals. Ensuring that parents accurately understand the limits to confidentiality and support the notion of confidential care for their children is a challenging yet vital task for health professionals.