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. WHAT THIS PAPER ADDS: The formulation of 320 µg/mL glycopyrronium significantly improved Drooling Impact Scale score versus placebo at day 84. The formulation reduced the impact of drooling on the child's and family's quality of life. There were no safety or tolerability concerns with this specific formulation.

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.

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.

Efficacy and Safety of the Local Application of Mitomycin C to Recurrent Esophageal Strictures in Children.

OBJECTIVES: Research on long-term use of mitomycin C (MC) for recurrent esophageal stenoses is limited. We assessed the long-term efficacy and safety of local application of MC for recurrent esophageal stenoses in children. METHODS: This was a retrospective study of 39 patients (17 girls) with a median age of 19.5 months (range: 2.4-196.0) at the time of MC application. The etiologies of stenosis were esophageal atresia (n = 25), caustic ingestion (n = 9), congenital esophageal stenosis (n = 3), and other causes (n = 2). Stenosis was single in 35 (90%) patients and multiple in 4 (10%). Before MC, patients underwent multiple repeated dilations (median: 3 dilations per child [range: 2-26]) over a median period of 7 months (range: 2.6-49.3). Treatment success was defined a priori as a reduction in the number of dilations over the same period from before to after the application of MC. RESULTS: For 26 (67%) patients, the application of MC was considered a success: 102 versus 17 dilatations (P < 0.0001). Sixteen (41%) patients never required additional dilation during the follow-up after MC application (median: 3.1 years [range: 0.6-8.5]). No complication related to MC was observed. Biopsies at the site of MC application were performed at maximal follow-up in 16 patients and revealed no dysplasia. Three factors were associated with success of MC: single stenosis, short stenosis, and esophageal atresia type III. CONCLUSIONS: This study is the largest series reported showing that topical application of MC is an efficient and safe treatment for recurrent esophageal stenosis in children.

Distances from vocal cords to mid-trachea for optimizing endotracheal tubes depth markers according to gestational age.

BACKGROUND: Adequate endotracheal tube positioning in preterm infants is complicated by the short length of the airway. Distal markers were designed to help with the insertion of endotracheal tubes at an appropriate depth below the vocal cords. However, those markers are not standardized between manufacturers, each tube size displays only one (sometimes 2) markers to provide information for infants of various gestational ages, and indicated distances are often too long for extremely preterm infants. AIMS: The study aims to describe vocal cords to mid-tracheal distance for different gestational ages and determine if depth markers should be adjusted accordingly. METHODS: Half the tracheal length added to the height of the posterior lamina of the cricoids approximates the distance between vocal cords and mid-trachea. Those dimensions were retrospectively retrieved from a database of laryngo-tracheal measurements obtained during autopsies of fetuses and newborn infants free of upper airway malformations. The equation of correlation between gestational age and distance from vocal cords to mid-trachea was used to calculate those distances for different gestational ages. RESULTS: Data were derived from 114 patients. Vocal cords to mid-trachea distance is linearly correlated with gestational age (r = .90; distance = 2.831 + 0.6208 × gestational age). We suggest depth markers at 17.7, 19.0, 20.8, 22.7, 24.6, and 26.4 mm for gestational ages of 24, 26, 29, 32, 35, and 38 weeks, respectively, indicated by contrasting colors. CONCLUSION: The linear relationship between laryngo-tracheal size and gestational age offers the opportunity to revise endotracheal tube depth markers for the smallest patients. Trials comparing those suggested markers with those currently in use are needed before implementation.

Laryngotracheal anomalies associated with esophageal atresia: importance of early diagnosis.

OBJECTIVE: Esophageal atresia (EA) is the most common congenital esophageal malformation. Airway pathology, in particular, tracheomalacia and laryngotracheal anomalies is a major cause of morbidity and mortalilty in patients with EA. The aim of this study was to report the incidence and type of laryngotracheal anomalies seen in a large series of patients with EA, and to evaluate their impact on the management of children with EA. STUDY DESIGN: Retrospective study. MATERIALS AND METHODS: Retrospective cohort including all patients referred to the EA National Reference Center from January 2002 to December 2014. Airway assessment was based on endoscopy performed before, during and/or after esophageal surgery. RESULTS: One-hundred and fifty-eight patients were included in the study. Endoscopy revealed tracheomalacia in 141 cases (89.2%) and other laryngotracheal anomalies in 43 patients (27.2%). Ninety-six patients (60.7%) presented with persistent respiratory symptoms, including acute life-threatening events in 21 cases, leading to death in 6 cases. A correlation was observed between degree of tracheal collapse and presence of acute life-threatening events. Laryngotracheal surgery was required in 35 cases (22%). CONCLUSION: Laryngotracheal anomalies are frequently associated with EA and represent an important etiology of morbidity and mortality that can be prevented by early and systematic diagnosis and aggressive management. An early systematic endoscopic evaluation is recommended to coordinate the airway management with the EA surgery.

Skin Patterns Associated with Upper Airway Infantile Haemangiomas: A Retrospective Multicentre Study.

The aim of this study was to define the skin patterns at high risk for upper airway infantile haemangioma. A retrospective multicentre French observational study was conducted between January 2006 and January 2015 and all confirmed airway haemangioma were included. Thirty-eight patients with airway haemangioma from 9 centres were included. Thirty-one patients had a cutaneous or mucosal haemangioma: 21 with a location considered at high risk for airway haemangioma (large segmental mandibular haemangioma), 4 with a very mild facial involvement (lower lip or S1 (frontotemporal segment according to Haggstrom and Frieden)) and 6 with either lesions of the neck or body, or association of both. We report here the largest cohort of airway haemangioma. A third of patients do not completely fit with the definition of the high-risk area of airway haemangioma. Segmental lower lip and neck involvement also seem to be very suggestive areas. Clinicians must be able to recognize these areas.

Association between Kniest dysplasia and chondrosarcoma in a child.

Constitutive COL2A1 mutations are associated with a wide variety of clinical manifestations known as type II collagenopathies. Among them is Kniest dysplasia, which is phenotypically variable and includes both skeletal (short trunk and limbs, kyphoscoliosis, prominent joints, and osteoarthritis) and craniofacial characteristics. Kniest dysplasia mutations primarily arise in the triple-helicoidal region of the alpha 1 (II) chain in COL2A1 between exons 12 and 24. Somatic COL2A1 mutations have been identified in chondrosarcoma, a rare cartilage forming neoplasm, with a hypermutability of the gene reported in 37% of cases. However, to the best of our knowledge, there is no reported increase in predisposition to chondrosarcoma in human collagenopathies, and no reported clinical association between these congenital diseases and cartilaginous tumors. In the case study presented here, we report the first description of an association between these two rare diseases involving COL2A1, in a child presenting with Kniest dysplasia and a grade I sphenoethmoidal chondrosarcoma. We also describe a new constitutive mutation in COL2A1.

Endoscopic repair of tracheoesophageal fistulas: A contemporary multi-institutional case series and literature review.

OBJECTIVES: Recurrent and primary tracheoesophageal fistulas (TEFs) are a challenging surgical pathology to treat, as standard open surgical approaches are associated with high morbidity and mortality. As such, endoscopic modalities have gained interest as an alluring alternative, yet variable success rates have been reported in the literature. The aim of this study was to provide a contemporary update of the literature and describe our institutional experience with the bronchoscopic obliteration of recurrent and primary TEFs. METHODS: Retrospective chart review of all pediatric patients having undergone endoscopic TEF repair at two pediatric academic centers in Montreal, Canada and Lille, France between January 1, 2008 to December 31, 2020. RESULTS: 28 patients with TEFs (20 recurrent, 8 primary) underwent a total of 48 endoscopic procedures. TEF repair was performed under endoscopic guidance using various combinations of techniques, including fistula de-epithelialization (endoscopic brush, thulium laser, trichloroacetic acid-soaked pledgets or electrocautery), tissue adhesives, submucosal augmentation, esophageal clip and stenting. Successful closure was achieved in 16 patients (57 %), while 12 (43 %) required eventual open or thoracoscopic repair. The mean number of endoscopic procedures was 1.7. There were no major treatment-related complications such as pneumothorax, mediastinitis or death (mean follow-up 50.8 months). CONCLUSIONS: Endoscopic repair of recurrent or primary TEFs is a valuable component of our therapeutic armamentarium and may contribute to decreased surgical morbidity in this complex patient population. Families should be counselled that endoscopic results may be more modest than with open or thoracoscopic approaches, and multiple procedures may be required.

Slide tracheoplasty for congenital tracheal stenosis: A systematic review.

INTRODUCTION: Slide tracheoplasty has become the gold standard surgery for congenital tracheal stenosis (CTS). This condition is rare and the surgery can be challenging and is performed by experienced surgeons in tertiary centers. A few reports involving relatively small cohorts have been published. The aim of this review is to evaluate the post-operative mortality and morbidity of pediatric slide tracheoplasty for CTS. METHODS: A systematic literature review was performed according to PRISMA guidelines. The Medline and EMBASE databases were screened using a search strategy defined in collaboration with a librarian. We included articles reporting the post-operative mortality rate of slide tracheoplasties for treatment of CTS in children, when at least 10 patients were included. RESULTS: A total of 932 articles were reviewed, and 15 studies were eligible with a total of 845 patients. The overall post-operative mortality rate was 9.3 %, and most deaths were airway related. The open revision surgery rate after surgery was 2.8 % and the endoscopic revision rate was 27.6 %. DISCUSSION: This study highlights key factors to consider before the surgery and helps anticipate post-operative follow-up considerations for children with CTS. Several factors were identified as predictors of mortality including young age, weight at the time of surgery and association with lung hypoplasia or aplasia. CONCLUSION: Although slide tracheoplasty has gained popularity in recent years due to better outcomes, it remains a major surgery with mortality risk and the need for multidisciplinary management.

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.

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.

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.

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.

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.

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.

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.

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.