Onasemnogene abeparvovec gene therapy for spinal muscular atrophy: A cohort study from the United Arab Emirates.

INTRODUCTION/AIMS: Spinal muscular atrophy (SMA) manifests with progressive motor neuron degeneration, leading to muscle weakness. Onasemnogene abeparvovec is a US Food and Drug Administration-approved gene replacement therapy for SMA. This study aimed to present short-term data of children in the United Arab Emirates (UAE) treated with onasemnogene abeparvovec, particularly in the context of children requiring invasive ventilatory support via tracheostomy. METHODS: A retrospective analysis was performed on 60 children who received onasemnogene abeparvovec. All these children received corticosteroids. They were followed up for up to 3 months. Motor function assessments were performed before and after the gene therapy. Comprehensive clinical evaluations, including pulmonary functions, were performed at baseline and the 3-month mark. RESULTS: Forty-three percent were male, and the mean age at the time of infusion was 29.6 months (SD ± 17.2). The mean weight was 10.1 kg (SD 2.6). All children demonstrated marked improvements in motor function within 3 months of gene therapy administration. No adverse effects attributable to corticosteroid therapy were observed. Positive clinical outcomes, including increased ventilator-free intervals, reduced antibiotic dependency, and fewer hospital admissions, were reported among children with invasive ventilation via tracheostomy. DISCUSSION: This study demonstrates the favorable tolerability and promising responses to onasemnogene abeparvovec in invasively ventilated pediatric patients. Early improvements in motor function, as observed within 3 months post-treatment, suggest its potential as a viable therapeutic option for this vulnerable patient population.

Subglottic Hemangioma: A Hidden Cause of an Infant's Respiratory Distress.

Subglottic hemangiomas are uncommon forms of infantile vascular tumors often misdiagnosed due to symptom overlap with other conditions like laryngomalacia, bronchiolitis, and asthma. Early and accurate diagnosis is vital for effective management. This case report discusses a unique presentation of subglottic hemangioma in a three-month-old infant, highlighting its diagnostic challenge and management. It adds valuable insights into the differentiation of subglottic hemangioma from other common causes of respiratory distress in infants. The infant presented with severe respiratory distress since birth, worsening over the last four weeks, accompanied by gastroesophageal reflux and poor weight gain. Initially, the case was suspected and treated as croup and laryngomalacia. A CT angiogram revealed a vascular lesion in the subglottic area, confirmed by flexible bronchoscopy as a hemangioma. Treatment with propranolol led to significant improvement. Early diagnosis and treatment of subglottic hemangioma are crucial for a good prognosis. This case emphasizes the importance of considering subglottic hemangioma in infants with unresolved airway distress.

Changes in UK paediatric long-term ventilation practice over 10 years.

OBJECTIVES: To provide up-to-date information on the use of long-term ventilation (LTV) in the UK paediatric population and to compare the results with data collected 10 and 20 years previously. DESIGN: A single timepoint census completed by LTV centres in the UK, carried out via an online survey. SETTING AND PATIENTS: All patients attending paediatric LTV services in the UK. RESULTS: Data were collected from 25 LTV centres in the UK. The total study population was 2383 children and young people, representing a 2.5-fold increase in the last 10 years. The median age was 9 years (range 0-20 years). Notable changes since 2008 were an increase in the proportion of children with central hypoventilation syndrome using mask ventilation, an increase in overall numbers of children with spinal muscular atrophy (SMA) type 1, chronic lung disease of prematurity and cerebral palsy being ventilated, and a 4.2-fold increase in children using LTV for airway obstruction. The use of 24-hour ventilation, negative pressure ventilation and tracheostomy as an interface had declined. 115 children had received a disease-modifying drug. The use of ataluren and Myozyme did not influence the decision to treat with LTV, but in 35% of the children with SMA type 1 treated with nusinersin, the clinician stated that the use of this drug had or may have influenced their decision to initiate LTV. CONCLUSION: The results support the need for national database for children and young people using LTV at home to inform future recommendations and assist in resource allocation planning.

Gastrostomies in children requiring long-term ventilation.

PURPOSE: Children requiring long-term ventilation (LTV) via tracheostomy often require enteral tube feeding. We sought to investigate what proportion of these children underwent gastrostomy insertion to inform decision making at time of tracheostomy formation. METHODS: A retrospective review of all children commenced on LTV via a tracheostomy at Royal Manchester Children's Hospital over a 9-year period (2012-2020). Data are presented as median [IQR]. RESULTS: Forty-one LTV patients had tracheostomy insertion with an average age of 167 days [101-604]. Reasons for tracheostomy insertion were upper airway obstruction (18), central neurological condition (7), neuromuscular condition (12) and lower respiratory tract disease (4). Twenty-two patients were born preterm and chronic lung disease of prematurity was a contributory factor in their requirement for LTV. Eight children had gastrostomies inserted prior to tracheostomy formation. A further 22 children had a gastrostomy inserted at an average of 139 days [99-227] following tracheostomy. Four children remained on nasogastric feed and the rest were fed orally. Seventy-three percentage of LTV children with tracheostomy were gastrostomy fed. Neither indication for LTV nor prematurity predicted whether a child was gastrostomy fed. CONCLUSION: The large majority of children requiring LTV are tube fed and gastrostomy insertion should be considered at time of formation of tracheostomy.

ERS statement on paediatric long-term noninvasive respiratory support.

Long-term noninvasive respiratory support, comprising continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV), in children is expanding worldwide, with increasing complexities of children being considered for this type of ventilator support and expanding indications such as palliative care. There have been improvements in equipment and interfaces. Despite growing experience, there are still gaps in a significant number of areas: there is a lack of validated criteria for CPAP/NIV initiation, optimal follow-up and monitoring; weaning and long-term benefits have not been evaluated. Therapeutic education of the caregivers and the patient is of paramount importance, as well as continuous support and assistance, in order to achieve optimal adherence. The preservation or improvement of the quality of life of the patient and caregivers should be a concern for all children treated with long-term CPAP/NIV. As NIV is a highly specialised treatment, patients are usually managed by an experienced paediatric multidisciplinary team. This statement written by experts in the field of paediatric long-term CPAP/NIV aims to emphasise the most recent scientific input and should open up new perspectives and research areas.

Association between electronic cigarette use in children and adolescents and coughing a systematic review.

BACKGROUND: The use of electronic cigarettes (e-cigarettes) among adolescents is increasing worldwide. E-cigarettes are marketed as a safe alternative to other tobacco products. The aim of this systematic review is to evaluate whether e-cigarette use in children and adolescents is associated with coughing. METHOD: Studies were identified through systematic searches of Excerpta Medica Database, Medline, Cumulative Index to Nursing and Allied Health Literature, British Nursing Index, OVID Emcare, Health Management Information Consortium, PsycINFO, and Allied and Complementary Medicine. The Grey Literature was also searched. Selected studies either contained only children and adolescents as study participants or if adults were included, the data for adolescents and children must be presented separately. RESULTS: Seven studies were selected from 104. Three studies compared e-cigarette users with nonusers; two studies found a significant association between coughing and e-cigarette use in adolescence. Two studies investigated whether adolescents attributed their symptoms to their e-cigarette use. One study reported that coughing was the most likely negative symptom reported by adolescents on initiation of e-cigarette use; the other study found that adolescents, on initiation of e-cigarette use, reported coughing. Two studies looked at the cases of children and adolescents who had presented to the hospital after e-cigarette use and found coughing was a common presenting symptom. CONCLUSION: This systematic review shows that adolescent use of e-cigarettes is associated with increased coughing and e-cigarette users are more likely to report coughing compared to non-users.

Unintentional exposure and incidental findings during conventional chest radiography in the pediatric intensive care unit.

ABSTRACT: Radiation overexposure is common in chest X-ray (CXRs) of pediatric patients. However, overexposure may reveal incidental findings that can help to guide patient management or warrant quality improvement.To assess the prevalence of overexposure in CXRs in pediatric intensive care unit (PICU); and identify the incidental findings within overexposed areas, we conducted a retrospective cohort study of children who were admitted to PICU. Two independent evaluators reviewed patient's charts and digital CXRs according to the American College of Radiology standards; to evaluate overexposure of the anatomical parameters and incidental findings.A total of 400 CXRs of 85 patients were reviewed. The mean number of CXRs per patient was 4.7. Almost all (99.75%) CXRs met the criteria for overexposure, with the most common being upper abdomen (99.2%), upper limbs (97%) and neck (95.7%). In addition, 43% of these X-rays were cropped by the radiology technician to appear within the requested perimeter. There was a significant association between field cropping and overexposure (t-test: t = 9.8, P < .001). Incidental findings were seen in 41.5% of the radiographs; with the most common being gaseous abdominal distension (73.1%), low-positioned nasogastric tube (24.6%), and constipation (10.3%).Anatomical overexposure in routine CXRs remains high and raises a concern in PICU practice. Appropriate collimation of the X-ray beam, rather than electronically cropping the image, is highly recommended to minimize hiding incidental findings in the cropped-out areas. Redefining the anatomic boundaries of CXR in critically ill infants and children may need further studies and consideration. Quality improvement initiatives to minimize radiation overexposure in PICU are recommended, especially in younger children and those with more severe illness upon PICU admission.

Updated cost-effectiveness analysis of palivizumab (Synagis) for the prophylaxis of respiratory syncytial virus in infant populations in the UK.

AIMS: Respiratory syncytial virus (RSV) is a common cause of respiratory infection in infants and severe infection can result in hospitalization. The passive immunization, palivizumab, is used as prophylaxis against RSV, however, use in the UK is restricted to populations at high risk of hospitalization. This study assesses the cost-effectiveness (CE) of palivizumab in premature infants with and without risk factors for hospitalization (congenital heart disease [CHD], bronchopulmonary dysplasia [BPD]). METHODS: A decision tree model, based on earlier CE analyses, was updated using data derived from targeted literature reviews and advice gained from a Round Table meeting. All costs were updated to 2019 prices. One-way and probabilistic sensitivity analyses were performed to assess the degree of uncertainty surrounding the results. RESULTS: Palivizumab is dominant (i.e. clinically superior and cost saving) when used in premature infants born ≤35 weeks gestational age (wGA) without CHD or BPD and aged <6 months at the start of the RSV season, infants aged <24 months with CHD and infants aged <24 months requiring treatment for BPD within the last 6 months. LIMITATIONS: One-way sensitivity analysis suggests that these results are highly sensitive to the efficacy of prophylaxis, number of doses, impact of long-term respiratory sequalae, rate of hospitalization and mortality due to RSV. A conservative approach has been taken toward long-term respiratory sequalae due to uncertainty around epidemiology and etiology and a lack of recent cost and utility data. CONCLUSIONS: Palivizumab prophylaxis is cost-effective in preventing severe RSV infection requiring hospital admission in a wider population than currently recommended in UK guidelines. Prophylaxis in premature infants born <29 wGA, 29-32 wGA and 33-35 wGA without CHD or BPD aged <6 months at the start of the RSV season is not funded under current guidance, however, prophylaxis has been demonstrated to be cost-effective in this analysis.

Characterization of tracheobronchomalacia in infants with hypophosphatasia.

BACKGROUND: Perinatal and infantile hypophosphatasia (HPP) are associated with respiratory failure and respiratory complications. Effective management of such complications is of key clinical importance. In some infants with HPP, severe tracheobronchomalacia (TBM) contributes to respiratory difficulties. The objective of this study is to characterize the clinical features, investigations and management in these patients. METHODS: We report a case series of five infants with perinatal HPP, with confirmed TBM, who were treated with asfotase alfa and observed for 3-7 years. Additionally, we reviewed respiratory function data in a subgroup of patients with perinatal and infantile HPP included in the clinical trials of asfotase alfa, who required high-pressure respiratory support (positive end-expiratory pressure [PEEP] ≥6 cm H2O and/or peak inspiratory pressure ≥18 cm H2O) during the studies. RESULTS: The case series showed that TBM contributed significantly to respiratory morbidity, and prolonged respiratory support with high PEEP was required. However, TBM improved over time, allowing weaning of all patients from ventilator use. The review of clinical trial data included 20 patients and found a high degree of heterogeneity in PEEP requirements across the cohort; median PEEP was 8 cm H2O at any time and some patients presented with high PEEP (≥8 cm H2O) over periods of more than 6 months. CONCLUSION: In infants with HPP presenting with persistent respiratory complications, it is important to screen for TBM and initiate appropriate respiratory support and treatment with asfotase alfa at an early stage. TRIAL REGISTRATION: ClinicalTrials.gov numbers: NCT00744042 , registered 27 August 2008; NCT01205152 , registered 17 September 2010; NCT01176266 , registered 29 July 2010.

Utility of open surgical lung biopsy in children.

INTRODUCTION: Open lung biopsy (OLB) is commonly used to obtain a definitive histological diagnosis in children with respiratory disorders. This allows correct treatment pathways to be followed and guides discussions surrounding prognosis. Our aim was to determine if OLB is useful in obtaining a conclusive diagnosis in a child with complex respiratory disease. MATERIALS AND METHODS: In total, 179 OLB episodes were identified in children under 18 years from 2006 to 2016. Biopsies confirming congenital thoracic malformations or pulmonary metastatic disease were excluded. RESULTS: 42 patients had 44 episodes of OLB in the period studied. A definitive histological diagnosis was reached in 35 (79%) cases. There were no deaths directly attributable to OLB surgery. CONCLUSION: OLB contributed substantially in obtaining a definitive diagnosis for our patient population, no increase in mortality. It allowed targeted treatment and provided valuable prognostic information on the likely progression of the disease so families could plan for palliation where appropriate.

Investigation of a Pandoraea apista cluster common to adult and paediatric cystic fibrosis patients attending two hospitals in the same city.

PURPOSE: We examined evidence for transmission of Pandorea apista among cystic fibrosis (CF) patients attending paediatric and adult services in one city who had previously been found to harbour related isolates by pulsed-field gel electrophoresis (PFGE). METHODOLOGY: The whole-genome sequences of 18 isolates from this cluster from 15 CF patients were examined, along with 2 cluster isolates from 2 other centres. The annotated sequence of one of these, Pa14367, was examined for virulence factors and antibiotic resistance-associated genes in comparison with data from a 'non-cluster' isolate, Pa16226. RESULTS: Single-nucleotide polymorphism (SNP) analysis suggested that cluster isolates from the same city differed from one another by a minimum of 1 and a maximum of 383 SNPs (an average of 213 SNPs; standard deviation: 18.5), while isolates from the 2 other hospitals differed from these by a minimum of 34 and 61 SNPs, respectively. Pa16226 differed from all cluster isolates by a minimum of 22 706 SNPs. Evidence for patient-to-patient transmission among isolates from the same city was relatively limited, although transmission from a common source could not be excluded. The annotated genomes of Pa14367 and Pa16226 carried putative integrative and conjugative elements (ICEs), coding for type IV secretion systems, and genes associated with heavy metal degradation and carbon dioxide fixation, and a wide selection of genes coding for efflux pumps, beta-lactamases and penicillin-binding proteins. CONCLUSION: Epidemiological analysis suggested that this cluster could not always be attributed to patient-to-patient transmission. The acquisition of ICE-related virulence factors may have had an impact on its prevalence.

rpoB gene sequencing highlights the prevalence of an E. miricola cluster over other Elizabethkingia species among UK cystic fibrosis patients.

Difficulties in distinguishing species of the Elizabethkingia genus by MALDI-TOF prompted use of rpoB sequencing to investigate species distribution among 44 isolates from cystic fibrosis (CF) patients. Forty-three isolates from 38 patients formed a cluster comprising E. miricola and proposed novel species E. bruuniana sp. nov., the exception clustering with proposed species E. ursingii sp. nov., also part of this wider cluster. All 44 isolates were PCR-positive for urease gene ureG, whereas only one of 23 E. anophelis isolates from non-CF patients was positive, suggesting that this gene is largely associated with the E. miricola cluster. Antibiotic susceptibilities of 12 CF isolates revealed all were resistant to beta-lactams with the exception of piperacillin-tazobactam, and were only susceptible to minocycline and co-trimoxazole. Pulsed-field gel electrophoresis analysis revealed 4 shared strains among 17 CF patients in one pediatric clinic, but epidemiological investigations did not support patient-to-patient transmission except between one sibling pair.

Developing a handheld record for patients with cystic fibrosis.

Patient handheld records (PHHRs) promote self-management and empower the holder to take a more active role in the management of their disease. They have been used successfully in improving preventative care for children and have contributed to improved adherence in a number of chronic illnesses. Despite the potential advantages, there are no standard PHHRs for patients with cystic fibrosis (CF). We report the consultation process that led to the development of a CF PHHR, describe the final document, and analyze the feedback from their use at our center. We have made the CF PHHR freely available online.

Republished: Accuracy in interpreting the paediatric ECG: a UK-wide study and the need for improvement.

BACKGROUND: Paediatric ECG interpretation is significant for informed treatment of several conditions. Formal training in paediatric ECG is rarely undertaken. METHODS: A prospective survey based study module of UK-wide paediatricians registered with the UK Royal College of Paediatricians and Child Health (RCPCH) was conducted. 10 common clinical conditions seen in paediatrics for which there are recognisable ECGs had to be interpreted. After provision of an educational page, 10 further ECGs were presented. FINDINGS: 8450 RCPCH members were emailed a link to the online survey-study module, of whom 764 participated. Of these, 493 interpreted the first 10 ECGs, and 385 interpreted both sets of ECGs. The accuracy for the first ECGs was 61.5% (63.5% for those who participated in the whole survey), and after use of the educational page increased to 73.3%. This was independent from previous ECG training. CONCLUSIONS: The use of an easily accessible online educational page improved the accuracy of paediatric ECG interpretation significantly. Internet based education can improve the accuracy of paediatric ECG interpretation and should be developed further.

Accuracy in interpreting the paediatric ECG: a UK-wide study and the need for improvement.

BACKGROUND: Paediatric ECG interpretation is significant for informed treatment of several conditions. Formal training in paediatric ECG is rarely undertaken. METHODS: A prospective survey based study module of UK-wide paediatricians registered with the UK Royal College of Paediatricians and Child Health (RCPCH) was conducted. 10 common clinical conditions seen in paediatrics for which there are recognisable ECGs had to be interpreted. After provision of an educational page, 10 further ECGs were presented. FINDINGS: 8450 RCPCH members were emailed a link to the online survey­study module, of whom 764 participated. Of these, 493 interpreted the first 10 ECGs, and 385 interpreted both sets of ECGs. The accuracy for the first ECGs was 61.5% (63.5% for those who participated in the whole survey), and after use of the educational page increased to 73.3%. This was independent from previous ECG training. CONCLUSIONS: The use of an easily accessible online educational page improved the accuracy of paediatric ECG interpretation significantly. Internet based education can improve the accuracy of paediatric ECG interpretation and should be developed further.