Developing a core outcome set for the health outcomes for children and adults with congenital oesophageal atresia and/or tracheo-oesophageal fistula: OCELOT task group study protocol.

INTRODUCTION: Heterogeneity in reported outcomes of infants with oesophageal atresia (OA) with or without tracheo-oesophageal fistula (TOF) prevents effective data pooling. Core outcome sets (COS) have been developed for many conditions to standardise outcome reporting, facilitate meta-analysis and improve the relevance of research for patients and families. Our aim is to develop an internationally-agreed, comprehensive COS for OA-TOF, relevant from birth through to transition and adulthood. METHODS AND ANALYSIS: A long list of outcomes will be generated using (1) a systematic review of existing studies on OA-TOF and (2) qualitative research with children (patients), adults (patients) and families involving focus groups, semistructured interviews and self-reported outcome activity packs. A two-phase Delphi survey will then be completed by four key stakeholder groups: (1) patients (paediatric and adult); (2) families; (3) healthcare professionals; and (4) researchers. Phase I will include stakeholders individually rating the importance and relevance of each long-listed outcome using a 9-point Likert scale, with the option to suggest additional outcomes not already included. During phase II, stakeholders will review summarised results from phase I relative to their own initial score and then will be asked to rescore the outcome based on this information. Responses from phase II will be summarised using descriptive statistics and a predefined definition of consensus for inclusion or exclusion of outcomes. Following the Delphi process, stakeholder experts will be invited to review data at a consensus meeting and agree on a COS for OA-TOF. ETHICS AND DISSEMINATION: Ethical approval was sought through the Health Research Authority via the Integrated Research Application System, registration no. 297026. However, approval was deemed not to be required, so study sponsorship and oversight were provided by Alder Hey Children's NHS Foundation Trust. The study has been prospectively registered with the COMET Initiative. The study will be published in an open access forum.

Recurrent croup is a good indicator of underlying paediatric airway issues: A 10-year retrospective cohort study of airway endoscopy.

OBJECTIVE: Children with a history of recurrent croup alert the ENT clinician to the potential for underlying laryngotracheal pathology. There is equipoise about the likelihood of identifying any underlying structural issues or subglottic stenosis in those children who undergo airway assessment. METHODS: A retrospective cohort study in a tertiary UK paediatric hospital of a decade of children with recurrent croup who underwent a rigid laryngo-tracheo-bronchoscopy (airway endoscopy). MAIN OUTCOME(S): airway pathology seen on endoscopy and need for further airway surgery. RESULTS: In ten years, 139 children underwent airway endoscopy for recurrent croup. Operative findings were abnormal in 62 (45 %) cases. Twelve cases (9%) had subglottic stenosis. Although recurrent croup was more common in males (78% of cases), this was not found to predispose them to operative findings. Children with previous intubations had >2 times the risk of abnormal findings and children born prematurely (<37 wks) had a trend towards abnormal operative findings versus children with no airway findings in our cohort. Even in those patients with abnormal findings, none necessitated further airway surgery. CONCLUSIONS: Surgeons and parents can be reassured that rigid airway endoscopy for children with recurrent croup demonstrated high diagnostic utility but will rarely lead to further surgical intervention. Greater understanding about recurrent croup may require consensus clarification about definitions of recurrent croup and/or a universal adoption of a minimum standard operative record or grading system after rigid endoscopy for recurrent croup.

Feeling stretched: Parents' narratives about challenges to resilience when their child has a tracheostomy.

This study aimed to examine how parents develop personal resilience when facing the challenges of caring for a child with tracheostomy. This study employed a longitudinal qualitative design. Unstructured narrative interviews with 12 parents (from nine families) whose child had a new tracheostomy were undertaken at three time points over 12 months. Data were analysed using a socio-narratology method. Findings reveal the journey parents experienced, how their feelings changed and the processes involved in developing resilience over the first 12 months of their child having a tracheostomy. Stories told by parents early in their journey revealed emotional upheaval, negative emotions, stress and shock. Due to medical need, parents had little or no choice for their child to have a tracheostomy. Once their child's life was out of danger, parents started to reframe their experiences and beliefs. Resilience played a major part in how parents perceived and faced their situation, allowing them to deal with what came their way and to move forward with their lives. Different aspects of resilience such as self-awareness, grit, gratitude, internal locus of control and reframing came to the fore at different time points. Parents talked feeling stretched by the challenges they faced and how they reframed their perspectives about their child's tracheostomy. Parents' resilience and reframing is discussed in relation to the ABC-X model. This study identifies a theoretical model that explains this process of change, this results in transferable knowledge, useful for understanding and explaining the experience of other parents and families.

Our experience in developing and operating the Airway Intervention Registry for Recurrent Respiratory Papillomatosis (AIR-RRP): national data collection [version 2; peer review: 2 approved].

Recurrent respiratory papillomatosis (RRP) is characterised by benign wart-like growths in the respiratory tract caused by the human papillomavirus (HPV). These warts vary in size and grow quickly, causing voice changes and airway obstruction. Whilst the condition is rare, RRP is more common and aggressive in children. There is currently no curative treatment for HPV, therefore RRP is managed by maintaining a safe airway and a serviceable voice by repeated surgery to remove the growths. A lack of specific diagnostic codes prevents reliable case ascertainment of RRP from routine administrative databases such as Hospital Episode Statistics. In 2017 a cross-sectional survey identified 918 RRP patients in the UK, half of whom had received surgical intervention for RRP in the previous 12 months with 16 different interventions. Randomised controlled trials for RRP interventions are difficult due to the rarity of the disease, variation in severity and progression and non-standard care across the NHS. Consequently, there is a lack of definitive efficacy and safety evidence. The only national guidance for RRP interventions is "Radiofrequency cold ablation for respiratory papillomatosis" (NICE IPG434, 2017) which recommended further data collection due to lack of evidence. However, due to the wide variation in RRP management across the NHS, clinical opinion favoured that any data collection should include a comparison of safety and efficacy of all RRP interventions in order to advise which improved patient outcomes and quality of life. To address lack of evidence, and inform the future care of RRP patients, we developed a registry and used it to collect real-world data from patients receiving treatment for RRP in NHS hospitals across the UK. The purpose of this paper is to share lessons learned from this national data collection exercise to inform future clinical registry development.

Foreign body impaction of the hard palate: tabletop party confetti mimicking button batteries in two infants.

We present the first two cases in the literature of tabletop party confetti mimicking button batteries in two infants. Both patients presented to the Emergency Department with an incidentally noticed shiny, metallic appearing, disc-shaped foreign body impacted in the hard palate. Both objects were understandably misdiagnosed as button batteries. The first patient required foreign body retrieval by ENT under general anaesthesia, whilst the second underwent retrieval safely in the Emergency Department. Tabletop party confetti should be considered in patients presenting with a suspected button battery impaction of the hard palate, which will drastically change the approach to clinical management and potentially minimise harms.

Pharmacotherapy for recurrent respiratory papillomatosis (RRP): a treatment update.

Introduction: Recurrent respiratory papillomatosis is a rare human papillomavirus (HPV)-induced condition where warts grow within the airway and especially the larynx to effect voice and restrict breathing.Areas covered: A PubMed search using the following search terms was performed: respiratory papillomatosis and cidofovir, alpha-interferon, bevacizumab, PD1, and HPV vaccines. Surgery remains the mainstay of treatment. There has been a change in options available for adjuvant therapies with systemic bevacizumab and the potential benefits of prophylactic HPV vaccine. Despite efforts to identify a drug therapy to control RRP, no therapy yet remains which is predictable and effective in all. The current status of therapeutic vaccines and immunotherapy is discussed.Expert opinion: The current adjuvant therapies do offer a reasonable expectation of control but the effect for the individual is unpredictable despite the therapies being based on good science. The current therapies would allow an escalating treatment strategy to be formulated, however a single therapy is unlikely to be curative. Multi-center trials are required such that adequate numbers to show an effect are achieved.

Paediatric tonsillectomy in England: A cohort study of clinical practice and outcomes using Hospital Episode Statistics data (2008-2019).

OBJECTIVES: To assess the safety of paediatric tonsillectomy procedures conducted in NHS hospitals in England between 2008 and 2019. DESIGN: Retrospective observational cohort study using Hospital Episode Statistics (HES) data. SETTING: Acute NHS trusts in England conducting paediatric tonsillectomy procedures. PARTICIPANTS: Children (≤16 years old) undergoing bilateral tonsillectomy. MAIN OUTCOME MEASURES: Number of tonsillectomies performed per year by procedural method. In-hospital complications including return to theatre for arrest of haemorrhage. Readmission within 28 days, including those for pain, haemorrhage and surgical arrest of haemorrhage. Long-term outcomes: all-cause mortality, revision tonsillectomy. RESULTS: A total of 318 453 paediatric tonsillectomies were performed from 2008 to 2019:278,772 dissection (87.5%) and 39 681 coblation (12.5%). The proportion of tonsillectomy performed using coblation increased from 7% in 2008/9 to 27% in 2018/9. Five patients died in hospital (including 4 due to respiratory complications). In-hospital complications occurred in 4202 children (1.3%), with the most frequent being haemorrhage. Within 28 days of tonsillectomy, 28 170 patients (8.8%) were readmitted and 7 deaths occurred. Readmission rates for haemorrhage and pain have increased since 2008. The proportion of children undergoing revision tonsillectomy procedures within 5 years following coblation tonsillectomy (1.4%) was approximately double that of dissection (0.6%). CONCLUSIONS: Clinical practice of paediatric tonsillectomy has changed in England over the past 11 years. The overall mortality rate associated with the procedure is 0.0037%. Differences in outcomes have been identified for different procedural methods. However, routine administrative data are limited in differentiating procedural detail (eg we are unable to differentiate intra or extra-capsular techniques from current clinical coding of tonsillectomy procedures). Therefore, prospective national data collection or more granular clinical coding is essential to capture relative outcomes of the different tonsillectomy methods and techniques being used in the NHS.

Holding Their Own and Being Resilient: Narratives of Parents over the First 12 Months of Their Child Having Tracheostomy.

Caring for a child with a tracheostomy can be challenging for parents and learning to safely manage their child's airway can be frightening due to their child's breathing issues, complex diagnosis and the difficult decisions they have to make. The aim of this longitudinal narrative study was to tell the stories of parents whose child had a new tracheostomy. Twenty three narrative interviews were conducted with twelve parents from nine families at three time points over a 12 month period. Data were analyzed using a socio-narratological approach. The stories told how parents were able to 'hold their own' despite experiencing shock, emotional upheaval and uncertainty during the period of their child's surgery. 'Holding their own' was possible for parents because resilience played an important part of their journey. Parents continued to be resilient as they adapted to being at home and dealt with ongoing challenging and stressful circumstances. All of the parents told stories reflecting on and recognizing that there were times when they exhibited higher levels of resilience and times when their resilience was lower. Looking back on their experiences parents appreciated that they reframed their initial often negative views about their child's need for a tracheostomy into more positive understandings and a future orientated perspective.

A core outcome set for research on the management of otitis media with effusion in otherwise-healthy children.

INTRODUCTION: A Core Outcome Set (COS) is an agreed list of outcome domains to be reported by all studies investigating a condition. A COS for Otitis Media with Effusion (OME) in children with cleft palate exists (called MOMENT), but there isn't one for otherwise-healthy children. This study investigates whether the MOMENT COS could also be applicable to otherwise-healthy children. METHODS: A long list of potential outcomes was generated (independently of MOMENT) via three methods: literature review to establish which outcomes are reported by OME studies, a review of outcomes contained in OME questionnaires, and a focus group asking parents of children with OME what matters to them. The long list drawn up using these sources identified no outcomes additional to ones in the MOMENT long list. An online questionnaire was subsequently undertaken, asking parents/guardians and professionals/researchers whether they think that the MOMENT final list outcomes would also be applicable to otherwise healthy children. RESULTS: A total of 134 people took part: 53 parents/guardians (recruited through UK NHS hospitals) and 81 professionals/researchers (recruited internationally). Overall, 128 (95.5%) agreed that the MOMENT outcomes can also apply to otherwise healthy children (100% parents/guardians, 92.6% professionals/researchers). CONCLUSIONS: The outcome domains identified in the COS for OME management in children with cleft palate can also be used in otherwise-healthy children.

Clinical outcomes of intracranial complications secondary to acute mastoiditis: The Alder Hey experience.

OBJECTIVE: Acute mastoiditis is the most common intra-temporal complication of acute otitis media. Its management remains a challenge due to potential extracranial and intracranial complications. This study was designed to evaluate the recent experience with acute mastoiditis and its associated intracranial complications at a tertiary paediatric centre. METHODS: A retrospective case note review was carried out for patients admitted to Alder Hey Children's Hospital between January 2006 and December 2016 with a diagnosis of acute mastoiditis. Patients were identified using ICD-10 codes H700, H701, H702, H708 and H709. A case note review was performed to identify patients with intracranial complications and data collected. RESULTS: 30 patients were identified with intracranial complications of acute mastoiditis, with 18 males and 12 females. The average age was 4 years and 2 months (range 2 months-15 years). The most common presenting complaint was otalgia and vomiting (63%), with only 27% patients presenting with mastoid swelling. 83% of patients were investigated with a combination of CT and MRI scans, 6.7% with CT scans only and 6.7% with MRI scans only. 73% were diagnosed with sinus thrombosis, 40% cerebral abscess and 33% postauricular subperiosteal abscess. 78% of the patients required surgical intervention. 27 of the 30 patients recovered fully with no significant long term sequalae following an average of 50 months follow-up. CONCLUSION: Intracranial complications of acute mastoiditis remain a significant challenge. Most patients tend to present without mastoid swelling, necessitating a high index of suspicion in patients with picket fence fever, vomiting, drowsiness, headaches, seizures or cranial nerve involvement. Most cases treated at our institution required acute surgical intervention in addition to adjuvant medical treatment with majority patients recovering fully.

Balloon dilatation for paediatric airway stenosis: Evidence from the UK Airway Intervention Registry.

OBJECTIVES: To assess the safety and efficacy in routine clinical practice of balloon dilatation procedures in the treatment of paediatric airway stenosis. DESIGN: Observational data collection in prospective online research database. SETTING: Acute NHS Trusts with ENT department undertaking complex paediatric airway work. PARTICIPANTS: Children (<18) undergoing balloon dilatation treatment for airway stenosis. MAIN OUTCOME MEASURES: Airway diameter, complications, hospital resource usage. RESULTS: Fifty-nine patients had 133 balloon procedures during 128 visits to 10 hospitals. Sixty-nine (52%) of balloon procedures were conducted with a tracheostomy. Intra-operative Cotton-Myer grade decreased in 43 (57%). The mean pre-balloon subglottic diameter was 4.2 [95% CI: 3.8 to 4.5] mm, and its rate of increase was 0.8 [0.5 to 1.2] mm per year modelled on 30 patients' long-term data. As the primary treatment of stenosis, the procedural success rate of balloon dilatation (n = 52) was 65% (22% with tracheostomy, 88% without tracheostomy), and 71% as an adjunct to open reconstructive surgery (n = 7). In the 64 hospital visits where a balloon procedure was conducted with a tracheostomy in place, only one in-hospital complication (lower respiratory tract infection) occurred. For those without a tracheostomy in place, in-hospital complications occurred in seven of 64 balloon hospital visits, all related to ongoing or worsening stenosis. Six out-of-hospital complications were deemed related to ongoing or worsening stenosis following the procedure, and two complications were a combination of lower respiratory infection and ongoing or worsening stenosis. CONCLUSIONS: Balloon dilation increases the size of the airway intraoperatively and is associated with long-term increase in airway diameter. Safety outcomes mostly relate to ongoing or worsening stenosis and are more common in patients without a tracheostomy.

Age at diagnosis, but not HPV type, is strongly associated with clinical course in recurrent respiratory papillomatosis.

BACKGROUND: Recurrent Respiratory Papillomatosis (RRP) is a rare disease characterized by the growth of papillomas in the airway and especially the larynx. The clinical course is highly variable among individuals and there is poor understanding of the factors that drive an aggressive vs an indolent course. METHODS: A convenience cohort of 339 affected subjects with papillomas positive for only HPV6 or HPV11 and clinical course data available for 1 year or more, from a large multicenter international study were included. Exploratory data analysis was conducted followed by inferential analyses with frequentist and Bayesian statistics. RESULTS: We examined 339 subjects: 82% were diagnosed prior to the age of 18 years, 65% were infected with HPV6, and 69% had an aggressive clinical course. When comparing age at diagnosis with clinical course, the probability of aggressiveness is high for children under five years of age then drops rapidly. For patients diagnosed after the age of 10 years, an indolent course is more common. After accounting for confounding between HPV11 and young age, HPV type was minimally associated with aggressiveness. Fast and Frugal Trees (FFTs) were utilized to determine which algorithms yield the highest accuracy to classify patients as having an indolent or aggressive clinical course and consistently created a branch for diagnostic age at ~5 years old. There was no reliable strong association between clinical course and socioeconomic or parental factors. CONCLUSION: In the largest cohort of its type, we have identified a critical age at diagnosis which demarcates a more aggressive from less aggressive clinical course.

Hoarseness in children.

Hoarseness or dysphonia are terms used to describe a change in the quality of the voice. The voice quality can be raspy, breathy, strained, fatigued, rough, tremulous or weak. There may be a change in pitch, restriction of range, voice breaks, decreased projection, or abnormal resonance. It is important to remember that a voice disorder is not a disease in itself but rather a presentation of an underlying pathology. Clinicians' knowledge of paediatric hoarseness is limited as it can be difficult to examine children using fibreoptic laryngoscopy and the child may not comprehend the need for detailed examination. However, paediatric flexible naso-laryngoscopy provides a dynamic view of the laryngeal anatomy and function. Recent advances in diagnostic equipment, pharmacology and therapeutics mean that this problem can be managed more successfully but it still remains a challenge. This article discusses the presentation, aetiology and management of hoarseness in children.

Potential risk factors associated with the use of cidofovir to treat benign human papillomavirus-related disease.

BACKGROUND: Cidofovir is currently being used off-licence to treat different viral infections, such as benign low-risk human papillomavirus (HPV)-related recurrent respiratory papillomatosis (RRP). There are concerns over the safety of this practice as rat studies demonstrated a high malignant transformation rate. As yet, there are no clinical reports of cidofovir-induced malignant changes in humans. METHODS: Telomerase immortalised human keratinocytes (hTert) stably expressing E6 proteins from either low-risk HPV6b or high-risk HPV16 and vector control cells were treated with either low-dose (5 microg/ml) or higher dose (30 microg/ml) cidofovir for 2 days and the effects evaluated by clonogenic survival assays. Based on these results, gene expression microarray analysis was performed on cidofovir-treated low-risk E6 and vector cells before, during and after drug treatment, and the results verified by real-time PCR. RESULTS: Both low-risk and high-risk E6-expressing cells show significantly improved long-term survival compared with vector control cells when exposed to 5 microg/ml cidofovir for 2 days, (hTert T6E6 P=0.0007, hTert T16E6 P=0.00023 and hTert vector control P=0.62). Microarray and real-time PCR analyses of low-dose cidofovir-treated low-risk E6-expressing cells revealed changes in gene expression that are known to be associated with malignant progression, which were not observed in drug-treated vector control cells. CONCLUSIONS: This is the first report that cidofovir can both increase cell survival and induce alterations in gene expression that are known to be associated with malignant transformation in cells transduced only with the E6 gene from low-risk HPV. It is our belief that these data provide cause for concern over the off-license use of this drug to treat RRP.

Cidofovir induces an increase in levels of low-risk and high-risk HPV E6.

BACKGROUND: Cidofovir is a nucleoside analogue that is used off-license to treat recurrent respiratory papillomatosis (RRP) caused by HPV6/11. However, the effect of this drug upon low-risk HPV 6/11 gene expression is unknown. METHODS: The expression of E6 was evaluated by RT-PCR in HPV-ve C33A cervical carcinoma cells stably transfected with both low- and high-risk HPV E6 cDNA's and in SiHa (HPV16+ve) cervical carcinoma cells after treatment with 2 doses and durations of exposure to cidofovir. RESULTS: Compared to the vector only transcript, E6 RNA levels showed an 8-fold increase in low-risk and 20-fold increase in high-risk E6-expressing cells. High-risk E6 protein levels were also detected by Western blot in cidofovir-treated C33A Type16 E6-transfected cells. CONCLUSION: These data may indicate a potential rationale for increased risk of genetic instability and thus transformation due to drug-induced increase in the level of E6.

Effects of cidofovir on a novel cell-based test system for recurrent respiratory papillomatosis.

BACKGROUND: Cidofovir has been reported to have activity against human papillomavirus (HPV) type 16, but no laboratory studies have been performed on HPV type 6, the main cause of recurrent respiratory papillomatosis (RRP). METHODS: HPV6b E6 cDNA-based C33A (non-HPV cervical carcinoma) cell line was produced. Two different doses of cidofovir were applied to parent C33A, C33AT6E6, and C33AT16E6 (HPV 16). Growth and flow cytometry analysis were performed. RESULTS: Polymerase chain reaction confirmed HPV6 E6 expression in C33AT6E6 cells. High-dose cidofovir was found to be toxic to all cell lines. Low-dose exposure was found to be toxic to C33AT16E6 cells at 3 days, whereas C33A and C33AT6E6 showed minimal toxicity at 6 days and earlier recovery following drug withdrawal. CONCLUSIONS: Cidofovir showed nonspecific toxicity against all 3 cell lines tested. HPV16 E6 expressing cells were more sensitive than parent or HPV6 E6 expressing cells. Cidofovir has no selective advantage for the RRP-related HPV6 E6 expressing cell line.