Glycopyrronium 320 µg/mL in children and adolescents with severe sialorrhoea and neurodisabilities: A randomized, double-blind, placebo-controlled trial.

AIM: To investigate the efficacy, safety, and impact on quality of life (QoL) of an oral formulation of 320 µg/mL glycopyrronium designed for children. METHOD: A double-blind, placebo-controlled SALIVA (Sialanar plus orAl rehabiLitation against placebo plus oral rehabilitation for chIldren and adolescents with seVere sialorrhoeA and neurodisabilities) trial was conducted. Children (3-17 years) with neurodisabilities and severe sialorrhoea (modified Teachers Drooling Scale ≥6) were randomized to 320 µg/mL glycopyrronium or placebo, in addition to non-pharmacological standard care. RESULTS: Of 87 participants, 44 were aged 10 years or under and 43 had cerebral palsy. The primary endpoint, change in total Drooling Impact Scale (DIS) score from baseline to day 84, was significantly greater (improved) with 320 µg/mL glycopyrronium versus placebo (median [quartile 1, quartile 3] -29.5 [-44.5, 0] vs -1 [-16, 5]; p < 0.001), an effect also observed at day 28 (median - 25 vs -2; p < 0.01). Significant reduction in bibs/clothes used per day was seen with glycopyrronium versus placebo at day 84 (median - 2 vs 0; p < 0.01). Glycopyrronium significantly improved DIS items 9 and 10 related to the extent that drooling affects the child's and family's life (p ≤ 0.03). Adverse events were reported by 77.3% and 69.8% of children with glycopyrronium and placebo respectively; the most common treatment-related adverse event was constipation (20.5% and 16.3%). INTERPRETATION: The formulation of 320 µg/mL glycopyrronium significantly improved drooling and reduced its impact on QoL, with good tolerability in children with neurodisabilities.

International pediatric otolaryngology group (IPOG) consensus on approach to aspiration.

OBJECTIVE: To provide recommendations for a comprehensive management approach for infants and children presenting with symptoms or signs of aspiration. METHODS: Three rounds of surveys were sent to authors from 23 institutions worldwide. The threshold for the critical level of agreement among respondents was set at 80 %. To develop the definition of "intractable aspiration," each author was first asked to define the condition. Second, each author was asked to complete a 5-point Likert scale to specify the level of agreement with the definition derived in the first step. RESULTS: Recommendations by the authors regarding the clinical presentation, diagnostic considerations, and medical and surgical management options for aspiration in children. CONCLUSION: Approach to pediatric aspiration is best achieved by implementing a multidisciplinary approach with a comprehensive investigation strategy and different treatment options.

Ultrasound assessment of endotracheal tube depth in neonates: a prospective feasibility study.

OBJECTIVE: To examine the reliability of a novel ultrasound (US) method for assessment of endotracheal tube (ETT) position in neonates. DESIGN: Prospective, observational, single-centre, feasibility study. SETTING: Level III neonatal intensive care unit. PATIENTS: Term and preterm neonates requiring endotracheal intubation. INTERVENTION: US measurement of the ETT tip to right pulmonary artery (RPA) distance was used to determine ETT position according to one-fourth to three-fourths estimated tracheal length for weight. US demonstration of pleural sliding and diaphragmatic movement was also assessed. Chest radiography (CXR) was performed following each intubation. MAIN OUTCOME MEASURES: Agreement between US assessment of ETT tip position and CXR served as the gold standard. Sensitivity, specificity, positive and negative predictive values for each US method and correlation between ETT tip to RPA distance on US, and ETT tip to carina distance on CXR were assessed. RESULTS: Forty-two US studies were performed on 33 intubated neonates. US evaluation of ETT-RPA distance identified 100% of ETTs positioned correctly: 77% deep and 80% high, demonstrating strong agreement with CXR (kappa=0.822). Sensitivity was 78%, specificity 100%, positive predictive value 100% and negative predictive value 86%. US ETT-RPA distance strongly correlated with CXR ETT-carina distance (r=0.826). No significant agreement was found between CXR and US assessment of pleural sliding and diaphragmatic movement. No adverse events were encountered during US scans. CONCLUSION: US evaluation of ETT-RPA distance demonstrated excellent accuracy for determining ETT position in neonates compared with CXR. More research is needed to support its feasibility in clinical settings.

International Pediatric Otolaryngology Group (IPOG) consensus on scoring of pediatric Drug Induced Sleep Endoscopy (DISE).

OBJECTIVES: To develop consensus statements for the scoring of pediatric drug induced sleep endoscopy in the diagnosis and management of pediatric obstructive sleep apnea. METHODS: The leadership group identified experts based on defined criteria and invited 18 panelists to participate in the consensus statement development group. A modified Delphi process was used to formally quantify consensus from opinion. A modified Delphi priori process was established, which included a literature review, submission of statements by panelists, and an iterative process of voting to determine consensus. Voting was based on a 9-point Likert scale. Statements achieving a mean score greater than 7 with one or fewer outliers were defined as reaching consensus. Statements achieving a mean score greater than 6.5 with two or fewer outliers were defined as near consensus. Statements with lower scores or more outliers were defined as no consensus. RESULTS: A total of 78 consensus statements were evaluated by the panelists at the first survey - 49 achieved consensus, 18 achieved near consensus, and 11 did not achieve consensus. In the second survey, 16 statements reached consensus and 5 reached near consensus. Regarding scoring, consensus was achieved on the utilization of a 3-point Likert scale for each anatomic site for maximal observed obstructions of <50% (Score 0, no-obstruction), ≥ 50% but <90% (Score 2, partial obstruction), and ≥ 90% (Score 3, complete obstruction). Anatomic sites to be scored during DISE that reached consensus or near-consensus were the nasal passages, adenoid pad, velum, lateral pharyngeal walls, tonsils (if present), tongue base, epiglottis, and arytenoids. CONCLUSION: This study developed consensus statements on the scoring of DISE in pediatric otolaryngology using a modified Delphi process. The use of a priori process, literature review, and iterative voting method allowed for the formal quantification of consensus from expert opinion. The results of this study may provide guidance for standardizing scoring of DISE in pediatric patients.

Randomised, double-blind, placebo-controlled trial of glycopyrronium in children and adolescents with severe sialorrhoea and neurodisabilities: protocol of the SALIVA trial.

INTRODUCTION: Severe sialorrhoea is a common, distressing problem in children/adolescents with neurodisabilities, which has adverse health and social consequences. The SALIVA trial is designed to evaluate the efficacy and safety of a paediatric-specific oral solution of glycopyrronium along with its impact on quality-of-life (QoL), which has been lacking from previous trials of sialorrhoea treatments. METHODS AND ANALYSIS: A double-blind, placebo-controlled, randomised phase IV trial is ongoing in several centres across France. Eighty children aged 3-17 years with severe sialorrhoea (≥6 on the modified Teachers Drooling Scale) related to chronic neurological disorders in whom non-pharmacological standard of care has already been implemented or has failed, will be recruited. Patients will be randomised 1:1 to receive a 2 mg/5 mL solution of glycopyrronium bromide (Sialanar 320 µg/mL glycopyrronium) or placebo three times daily during a 3-month blinded period. After Day 84, participants will be invited into a 6-month, open-label study extension period, where they will all receive glycopyrronium. The primary endpoint of the double-blind period will be the change from baseline to Day 84 in the Drooling Impact Scale (DIS), a validated measure to assess sialorrhoea. A series of secondary efficacy endpoints involving change in total DIS, specific DIS items and response (DIS improvement ≥13.6 points) will be analysed in a prespecified hierarchy. QoL data will be collected from parents, caregivers and patients where possible using specific DIS questions and DISABKIDS questionnaires. Safety endpoints, including adverse events, will be assessed throughout the trial periods. ETHICS AND DISSEMINATION: In total, 87 children have been recruited and recruitment is now complete. Final results are expected by the end of 2023. Findings will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EudraCT 2020-005534-15.

Development of an international glossary for clinical guidelines collaboration.

OBJECTIVES: Clinical practice guidelines (CPGs) are often created through collaboration among organizations. The use of inconsistent terminology may cause poor communication and delays. This study aimed to develop a glossary of terms related to collaboration in guideline development. STUDY DESIGN AND SETTING: A literature review of collaborative guidelines was performed to develop an initial list of terms related to guideline collaboration. The list of terms was presented to the members of the Guideline International Network Guidelines Collaboration Working Group, who provided presumptive definitions for each term and proposed additional terms to be included. The revised list was subsequently reviewed by an international, multidisciplinary panel of expert stakeholders. Recommendations received during this pre-Delphi review were implemented to augment an initial draft glossary. The glossary was then critically evaluated and refined through two rounds of Delphi surveys and a virtual consensus meeting with all panel members as Delphi participants. RESULTS: Forty-nine experts participated in the pre-Delphi survey, and 44 participated in the two-round Delphi process. Consensus was reached for 37 terms and definitions. CONCLUSION: Uptake and utilization of this guideline collaboration glossary by key organizations and stakeholder groups may facilitate collaboration among guideline-producing organizations by improving communication, minimizing conflicts, and increasing guideline development efficiency.

Comprehensive management of anterior drooling: An International Pediatric Otolaryngology Group (IPOG) consensus statement.

OBJECTIVE: To provide guidance for the comprehensive management of children referred for anterior drooling. The mission of the International Pediatric Otolaryngology Group (IPOG) is to develop expertise-based recommendations for the management of pediatric otolaryngologic disorders with the goal of improving patient care. METHODS: Survey of expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG). The recommendations are derived from current expert consensus and critical review of the literature. RESULTS: Consensus recommendations include initial care and approach recommendations for health care providers who commonly evaluate children with drooling. This includes evaluation and treatment considerations for commonly debated issues in drooling management, initial work-up of children referred for anterior drooling, treatment recommendations, indications and contra-indications for rehabilitation, medical, and surgical management, as well as pros and cons of different surgical procedures in the hands of drooling management experts. CONCLUSION: Anterior drooling consensus recommendations are aimed at improving patient-centered care in children referred for sialorrhea.

Evaluation of thyroplasty with cartilage implant in young children.

OBJECTIVE: To evaluate thyroplasty with autologous cartilage implant in young children. METHODS: This retrospective study included all patients aged <10 years who underwent thyroplasty, in a tertiary care center, between 1999 and 2019 and had a postoperative follow-up at least one year later. Morphological evaluation was based on fiberoptic laryngoscopy and laryngeal ultrasound. Functional outcomes included parental evaluation of laryngeal signs by visual analogue scale and dysphonia ratings on the Grade, Roughness, Breathiness, Asthenia, and Strain scale. These assessments were performed at postoperative months 1, 6, and 12, and then annually. RESULTS: Participants were 11 patients with a median age of 26 months (8-115 months). Their median duration of progression of paralysis before surgical management was 17 months. No intra or postoperative complications were observed. Postoperative evaluation showed virtual disappearance of aspiration and chronic congestion. Voice evaluation revealed significant improvements in all patients. The long-term trend, over a median of 77 months, showed stable results in 10 cases. One patient had late-onset deterioration requiring an additional vocal fold injection. Ultrasound follow-up showed no resorption of the cartilage implant and no deformation of the thyroid ala. CONCLUSION: Pediatric thyroplasty requires technical adaptations. Use of a cartilage implant allows observation of medialization stability during the growth. These findings are particularly relevant of contraindication or failure of nonselective reinnervation.

International Pediatric Otolaryngology Group: Consensus guidelines on the diagnosis and management of non-tuberculous mycobacterial cervicofacial lymphadenitis.

INTRODUCTION: Non-tuberculous mycobacterial (NTM) infection commonly manifests as subacute or chronic cervicofacial lymphadenitis in immunocompetent children. The optimal management of this pathology remains controversial. OBJECTIVES: This international consensus guideline aims to understand the practice patterns for NTM cervicofacial lymphadenitis and to address the primary diagnostic and management challenges. METHODS: A modified three-iterative Delphi method was used to establish expert recommendations on the diagnostic considerations, expectant or medical management, and operative considerations. The recommendations herein are derived from current expert consensus and critical review of the literature. SETTING: Multinational, multi-institutional, tertiary pediatric hospitals. RESULTS: Consensus recommendations include diagnostic work-up, goals of treatment and management options including surgery, prolonged antibiotic therapy and observation. CONCLUSION: The recommendations formulated in this International Pediatric Otolaryngology Group (IPOG) consensus statement on the diagnosis and management of patients with NTM lymphadenitis are aimed at improving patient care and promoting future hypothesis generation.

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Evaluation and management of congenital tracheal stenosis.

OBJECTIVES: To outline an expert-based consensus of recommendations for the diagnosis and management of pediatric patients with congenital tracheal stenosis. METHODS: Expert opinions were sought from members of the International Pediatric Otolaryngology Group (IPOG) via completion of an 18-item survey utilizing an iterative Delphi method and review of the literature. RESULTS: Forty-three members completed the survey providing recommendations regarding the initial history, clinical evaluation, diagnostic evaluation, temporizing measures, definitive repair, and post-repair care of children with congenital tracheal stenosis. CONCLUSION: These recommendations are intended to be used to support clinical decision-making regarding the evaluation and management of children with congenital tracheal stenosis. Responses highlight the diverse management strategies and the importance of a multidisciplinary approach to care of these patients.

Locoregional Control and Survival in Children, Adolescents, and Young Adults With Localized Head and Neck Alveolar Rhabdomyosarcoma-The French Experience.

INTRODUCTION: The head and neck (HN) are the most frequent sites of pediatric rhabdomyosarcoma (RMS). Alveolar RMS (ARMS) represents ~20% of all RMS cases and frequently spread to lymph nodes (LNs). The aim was to report locoregional control, event-free survival (EFS), and overall survival (OS), according to clinical and pathological features, LN staging, and treatment modalities. METHODS: The study included all patients prospectively enrolled in EpSSG RMS 2005 study under 21 years of age with localized HN ARMS and diagnosed between 2005 and 2016 in France. Medical data including imaging, surgical report, and radiation therapy planes were analyzed. RESULTS: Forty-eight patients (median age 6 years; range 4 months-21 years), corresponding to 30 parameningeal and 18 non-parameningeal ARMS, were included. There were 33 boys (69%). Tumor locations included the following: orbit (n = 7) among which four cases had bone erosion, paranasal sinuses and nasal cavity (n = 16), deep facial spaces (n = 10), nasolabial fold (n = 8), and other non-parameningeal HN sites (n = 7). A fusion transcript of PAX3-FOXO1 or PAX7-FOXO1 was expressed in 33 of the 45 cases (73%) with molecular analysis. At diagnosis, 10 patients had primary resection of the primary tumor (PRPT) (none with microscopic complete resection) and 9 had LN staging. After induction chemotherapy, 26 patients (54%) had secondary resection of the primary tumor (SRPT) and 13 patients (27%) had cervical LN dissection. A total of 43 patients (90%) were treated with radiation therapy.With a median follow-up of 7 years (range 2-13 years), 5-year OS and EFS were 78% (95% CI, 63-88%) and 66% (95% CI, 51-78%), respectively. We observed 16 events (10 deaths): 4 local, 4 regional, 1 local and regional, and 7 metastatic. In univariate analysis, OS was only superior for patients under 10 years of age (p = 0.002), while FOXO1-negative ARMS, SRPT for parameningeal ARMS, and LN surgery were associated with significantly better EFS. CONCLUSION: Our study confirms a better outcome for fusion-negative ARMS and ARMS in children under 10 years. Moreover, LN surgery and SRPT of parameningeal tumor may improve EFS of ARMS. Larger studies are needed to confirm our findings.

International Pediatric Otolaryngology Group (IPOG) management recommendations: Pediatric tracheostomy decannulation.

OBJECTIVES: To provide recommendations to otolaryngologists, pulmonologists, and allied clinicians for tracheostomy decannulation in pediatric patients. METHODS: An iterative questionnaire was used to establish expert recommendations by the members of the International Pediatric Otolaryngology Group. RESULTS: Twenty-six members completed the survey. Recommendations address patient criteria for decannulation readiness, airway evaluation prior to decannulation, decannulation protocol, and follow-up after both successful and failed decannulation. CONCLUSION: Tracheostomy decannulation recommendations are aimed at improving patient-centered care, quality and safety in children with tracheostomies.

International Pediatric Otolaryngology Group (IPOG) survey: Efforts to avoid complications in home tracheostomy care.

OBJECTIVE: To provide guidance for home care tracheostomy management in the pediatric population. The mission of the IPOG is to develop expertise-based recommendations for the management of pediatric otolaryngologic disorders with the goal of improving patient care. METHODS: Survey of expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG). RESULTS: Survey results provide guidance for caregiver teaching, the reuse of tracheostomies and suction catheters while inpatient and following discharge, acceptable sterilization practices for tracheostomies, tracheitis workup and management, and outpatient follow-up practices. CONCLUSION: This presentation of common home tracheostomy care practices are aimed at improving patient-centered care in the pediatric population.

Experience with laryngeal reinnervation using nerve-muscle pedicle in pediatric patients.

OBJECTIVE: Vocal fold paralysis (VFP) in adducted position remains a challenge for airway surgeons. Alternatives to tracheostomies such as lateralization, cordectomy, and posterior rib grafting disrupt the laryngeal tissue or framework and carry an increased risk of aspiration. Laryngeal reinnervation using nerve-muscle pedicle (NMP), carries the distinct advantage of preserving the larynx, sparing the recurrent laryngeal nerve, and obtaining an active VF abduction. The aim of this study was to evaluate the success and complications of laryngeal reinnervation using nerve-muscle pedicle (NMP) in pediatric patients presenting with dyspnea related to VFP in adducted position. METHODS: In this case series performed at a tertiary care referral center, review of medical records on all pediatric patients with VFP in adduction treated with laryngeal reinnervation using NMP between 1999 and 2017. Data were collected on the preoperative flexible laryngoscopy, suspension micro-laryngoscopy, and laryngeal electromyography as well as post-operative clinical assessment of the voice and airway. All patients underwent surgery consisting of the transfer of an innervated omohyoid muscle pedicle onto the paralyzed posterior cricoarytenoid muscle. The main outcomes measured were the clinical and fiberoptic laryngoscopic airway assessment monthly for the first 6 months, then at 12 months and annually thereafter. Clinical assessment included dyspnea evaluation based on a visual analog scale and voice assessment using the GRBAS scores. Complications from the treatment were also noted. These outcomes were determined before collection of data. RESULTS: 16 cases were identified, with a mean age of 4 years. The recurrent laryngeal nerve paralysis was bilateral in 3 cases and unilateral in 13 cases. There were no peri or postoperative complications. After a mean follow-up of 7 years, vocal fold abduction was observed in 10 out of 16 cases and disappearance of paradoxical inspiratory adduction in 3 cases. Persistent dyspnea was noted in 7 cases (44%), and moderate dysphonia was present in 11 cases (69%). Finally, additional procedures were necessary in 2 patients (13%) to achieve the outcomes. CONCLUSIONS: Laryngeal reinnervation using NMP may be used in pediatric patients. This procedure, is safe and allows us to spare the recurrent laryngeal nerve while obtaining an active VF abduction in the majority of cases, and an improvement in breathing in most cases. QUALITY OF EVIDENCE: 4.

International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Management of suprastomal collapse in the pediatric population.

INTRODUCTION: Suprastomal Collapse (SuStCo) is a common complication of prolonged tracheostomy in children. There is a paucity of literature on this subject, especially regarding how to manage significant suprastomal collapse that prevents safe decannulation. OBJECTIVE: Provide a definition, classification system, and recommend management options for significant suprastomal collapse in children with tracheostomy. METHODS: Members of the International Pediatric Otolaryngology Group (IPOG) who are experts in pediatric airway conditions were surveyed and results were refined using a modified Delphi method. RESULTS: Consensus was defined as > 70% agreement on a subject. The experts achieved consensus: CONCLUSION: This consensus statement provides recommendations for medical specialists who manage infants and children with tracheostomies with significant Suprastomal Collapse. It provides a classification system to facilitate diagnosis and treatment options for this condition.

International Pediatric Otolaryngology Group (IPOG): Consensus recommendations on the prenatal and perinatal management of anticipated airway obstruction.

OBJECTIVE: To make recommendations on the identification, routine evaluation, and management of fetuses at risk for airway compromise at delivery. METHODS: Recommendations are based on expert opinion by members of the International Pediatric Otolaryngology Group (IPOG). A two-iterative Delphi method questionnaire was distributed to all members of the IPOG and responses recorded. The respondents were given the opportunity to comment on the content and format of the survey, which was modified for the second round. "Consensus" was defined by >80% respondent affirmative responses, "agreement" by 51-80% affirmative responses, and "no agreement" by 50% or less affirmative responses. RESULTS: Recommendations are provided regarding etiologies of perinatal airway obstruction, imaging evaluation, adjunct evaluation, multidisciplinary team and decision factors, micrognathia management, congenital high airway obstruction syndrome management, head and neck mass management, attended delivery procedure, and delivery on placental support procedure. CONCLUSIONS: Thorough evaluation and thoughtful decision making are required to optimally balance fetal and maternal risks/benefits.

International Pediatric ORL Group (IPOG) Robin Sequence consensus recommendations.

OBJECTIVE: To provide recommendations for the comprehensive management of airway obstruction in patients with Robin Sequence. METHODS: Expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG). RESULTS: The consensus statement provides recommendations for medical specialists who manage infants with Robin Sequence including: evaluation and treatment considerations for commonly debated issues in post-natal airway obstruction, assessment of antenatal obstruction and perinatal airway management. CONCLUSION: Consensus recommendations are aimed at improving management of airway obstruction in patients with Robin Sequence.

Developmental changes of upper airway dimensions in children.

BACKGROUND: Knowledge about airway dimensions during child growth is of paramount importance for pediatric clinical practice. Decisions about airway management in children are based on relatively limited, imprecise, or incomplete data about airway size. AIMS: The aim of this work was to determine the anatomical development and size of airway structures from birth to adolescence using high-resolution computed tomography scans and to study the correlation between airway measurements and biometric data. METHODS: We conducted a retrospective study of all high-resolution computed tomography scans including the respiratory tract, performed in our tertiary pediatric center (for reasons unrelated to airway symptoms) between June 1, 2016, and October 15, 2017, on children aged from 1 day to 14 years old. On each scan, 23 measurements of the larynx, trachea, and mainstem bronchi were performed. Patients were stratified into 16 groups according to their age. We calculated median value for each measurement in each group. Statistical models were calculated to explore correlation between measurements and age or weight. RESULTS: A total of 192 scans were included (127 boys/65 girls). The mean age was 7 years. The correlations between airway measurements and age or weight were always significant. The relationship between measurements and age was found to be suitably represented by a cubic polynomial equation suggesting that the airway has a rapid growth phase in the first 3 years, followed by a slow growth phase and a second rapid growth phase during adolescence. The most relevant biometric parameter was age concerning 21 of the measurements. CONCLUSION: This comprehensive anatomical database of upper airway dimensions provides important data in the field of pediatric airway anatomy, particularly relating to the cricoid. We demonstrated that laryngeal, tracheal, and bronchial parameters correlate better to age and have three different growth phases.

Bronchopulmonary and vascular anomalies are frequent in children with oesophageal atresia.

AIM: Oesophageal atresia is frequently associated with other malformations, and our aim was to use computed tomography (CT) to explore intrathoracic malformations in patients with this condition. METHOD: This was retrospective study of children aged 0-16 with oesophageal atresia who were born in 1996-2013 and followed up at the French reference centre for rare oesophageal diseases at the University of Lille. Computed tomography scans were available for 48 of the 234 patients during follow-up visits, and these were reviewed by a thoracic radiologist. RESULTS: More than two-thirds of the scans were performed to explore persistent respiratory symptoms. We found that six patients had a pulmonary malformations: four lobar agenesis, one right pulmonary aplasia and one congenital cystic adenomatoid malformation. Computed tomography enabled us to diagnose unexpected thoracic malformations in 16 patients: four lobar agenesis, six arteria lusoria, five persistent left superior vena cava and one partial anomalous pulmonary venous return. It also confirmed the diagnoses of suspected malformations in five patients: one congenital cystic adenomatoid malformation, one pulmonary hypoplasia, two right-sided aortic arches and one communicating bronchopulmonary foregut malformation. CONCLUSION: Intrathoracic anomalies were frequently associated with oesophageal atresia, and contrast-enhanced chest CT scans should be performed on patients with persistent respiratory symptoms.