Interdisciplinary assessment and treatment of paediatric drooling: two decades of experience by the Nijmegen saliva control team reflected in a stepwise algorithm.

Anterior and posterior drooling are prevalent comorbidities in children with neurodevelopmental disabilities. Considering the heterogeneity of the patient population and the multifactorial aetiology of drooling, an interdisciplinary and individualised treatment approach is indispensable. However, no tool for stepwise decision-making in the treatment of paediatric drooling has been developed previously. Within the Radboudumc Amalia Children's Hospital, care for children with anterior and/or posterior drooling secondary to neurodevelopmental disabilities is coordinated by a saliva control team with healthcare professionals from six disciplines. In alignment with international literature, published guidelines, and evidence gained from two decades of experience and research by our team, this paper proposes an algorithm reflecting the assessment and treatment approach applied in our clinic. First, directions are provided to decide on the necessity of saliva control treatment, taking type of drooling, the child's age, and the severity and impact of drooling into account. Second, the algorithm offers guidance on the choice between available treatment options, highlighting the importance of accounting for child characteristics and child and caregiver preferences in clinical (shared) decision-making. CONCLUSIONS: With this algorithm, we aim to emphasise the importance of repeated stepwise decision-making in the assessment and treatment of drooling in children during their childhood, encouraging healthcare professionals to apply a holistic approach. WHAT IS KNOWN: • Children with anterior or posterior drooling secondary to neurodevelopmental disabilities comprise a heterogeneous group, necessitating an individualised treatment approach. • No stepwise decision-making tool is available for the treatment of paediatric drooling. WHAT IS NEW: • Deciding on the necessity of saliva control treatment should be a conscious process, based on type of drooling, age, and drooling severity and impact. • Type of drooling, age, cognition, oral motor skills, self-awareness, posture, diagnosis, and child/caregiver preferences need to be considered to decide on the optimal treatment.

The when, why, and how of using glycopyrronium to diminish drooling in children with neurodevelopmental disabilities: Implications for clinical practice.

BACKGROUND: Despite the established efficacy of glycopyrronium bromide in reducing drooling among children with neurodevelopmental disabilities, evidence on its impact on the daily lives of children and parents and effectiveness in a real-world setting are scarce, especially among long-term users. This study explored timing and duration of glycopyrronium treatment, effect and impact on daily life, and occurrence of side effects to inform clinical practice. METHODS: This was a retrospective cohort study at a national referral centre for drooling, including 61 children with nonprogressive neurodevelopmental disabilities, treated with glycopyrronium for anterior and/or posterior drooling between 2011 and 2021. Data were obtained from medical records and supplemented by structured telephone interviews with parents. RESULTS: Anterior drooling severity decreased in 82% of the included children. Changes in the impact of drooling on burden of care, social interaction, and self-esteem were reported in 55%, 31%, and 36%, respectively. Side effects were noted for 71% of cases, yet only 36% of parents deemed these as outweighing the positive impact of treatment. A substantial majority (77%) of the included children were long-term users (≥6 months). Among these, 38% of parents reported decreasing effectiveness and 27% noticed more prominent side effects over time. CONCLUSIONS: Glycopyrronium demonstrated potential in mitigating the impact of drooling on daily life, although variations were observed in the specific aspects and extent of improvement. The real-world context of our study provides important insights for refining clinical practices, emphasizing the need for balanced consideration of treatment benefits and potential side effects to facilitate shared decision-making.

Comparing the evidence for botulinum neurotoxin injections in paediatric anterior drooling: a scoping review.

Paediatric anterior drooling has a major impact on the daily lives of children and caregivers. Intraglandular botulinum neurotoxin type-A (BoNT-A) injections are considered an effective treatment to diminish drooling. However, there is no international consensus on which major salivary glands should be injected to obtain optimal treatment effect while minimizing the risk of side effects. This scoping review aimed to explore the evidence for submandibular BoNT-A injections and concurrent submandibular and parotid (i.e. four-gland) injections, respectively, and assess whether outcomes could be compared across studies to improve decision making regarding the optimal initial BoNT-A treatment approach for paediatric anterior drooling. PubMed, Embase, and Web of Science were searched to identify relevant studies (until October 1, 2023) on submandibular or four-gland BoNT-A injections for the treatment of anterior drooling in children with neurodevelopmental disabilities. Similarities and differences in treatment, patient, outcome, and follow-up characteristics were assessed. Twenty-eight papers were identified; 7 reporting on submandibular injections and 21 on four-gland injections. No major differences in treatment procedures or timing of follow-up were found. However, patient characteristics were poorly reported, there was great variety in outcome measurement, and the assessment of side effects was not clearly described.   Conclusion: This review highlights heterogeneity in outcome measures and patient population descriptors among studies on paediatric BoNT-A injections, limiting the ability to compare treatment effectiveness between submandibular and four-gland injections. These findings emphasize the need for more extensive and uniform reporting of patient characteristics and the implementation of a core outcome measurement set to allow for comparison of results between studies and facilitate the optimization of clinical practice guidelines. What is Known: • There is no international consensus on which salivary glands to initially inject with BoNT-A to treat paediatric drooling. What is New: • Concluding on the optimal initial BoNT-A treatment based on literature is currently infeasible. There is considerable heterogeneity in outcome measures used to quantify anterior drooling.and clinical characteristics of children treated with intraglandular BoNT-A are generally insufficiently reported. • Consensus-based sets of outcome measures and patient characteristics should be developed and implemented.

Predicting non-response to intraglandular botulinum neurotoxin A injections for drooling in children with neurodevelopmental disabilities.

AIM: To develop robust multivariable prediction models for non-response to (1) submandibular botulinum neurotoxin A (BoNT-A) injections and (2) concurrent submandibular and parotid (four-gland) injections, to guide treatment decisions for drooling in children with neurodevelopmental disabilities, including cerebral palsy. METHOD: This was a retrospective cohort study including 262 children (155 males/107 females, median age 7 years 11 months [IQR 5 years 1 month], range 4 years 0 months - 17 years 11 months) receiving submandibular injections and 74 children (52 males/22 females, median age 7 years 7 months [IQR 4 years 3 months], range 4 years 9 months - 18 years 8 months) receiving four-gland injections. Multivariable logistic regression analyses were used to estimate associations between candidate predictors and non-response 8 weeks after injection. RESULTS: Ninety-six children (37%) were non-responders to submandibular injections, for which developmental age was the strongest predictor (adjusted odds ratio [aOR] 2.13; 95% confidence interval [CI] 1.02-4.45 for developmental age <4 years or 4-6 years with IQ <70). Other characteristics that showed a trend towards an increased risk of non-response were diagnosis, sex, and head position. Thirty-four children (46%) were non-responders to four-gland injections, for which tongue protrusion (aOR 3.10; 95% CI 1.14-8.43) seemed most predictive, whereas multiple preceding submandibular injections (aOR 0.34; 95% CI 0.10-1.16) showed a trend towards being protective. Predictors were, however, unstable across different definitions of non-response and both models (i.e. submandibular and four-gland) had insufficient discriminative ability. INTERPRETATION: Potential predictors of non-response to BoNT-A injections were identified. Nevertheless, the developed prediction models seemed inadequate for guidance of treatment decisions. WHAT THIS PAPER ADDS: Developmental age seemed most predictive of non-response to submandibular botulinum neurotoxin A injections. Non-response to concurrent submandibular and parotid injections was best predicted by tongue protrusion and number of previous injections. Multivariable prediction models including these clinical characteristics were unable to discriminate well. Predictors differed when non-response was defined using alternative outcome measures.

Recognising symptoms of congenital myasthenic syndromes in children: A guide for paediatricians.

AIM: Congenital myasthenic syndromes (CMS) are a rare and diverse group of treatable neuromuscular transmission disorders. Diagnosis is often substantially delayed. This study aimed to identify common symptoms of CMS in children and their manifestation to aid diagnosis and early intervention. METHODS: We performed a retrospective cohort study, including 18 children (median age 13 years, range 9 years 5 months-18 years 0 month) with CMS. Data on CMS symptoms and their manifestation were extracted from patients' charts and supplemented with parental telephone interviews. Descriptive analyses were used to identify common symptoms. RESULTS: A median diagnostic delay of 4 years and 7 months (interquartile range: 51 months) was observed. Proximal muscle weakness (100%), ptosis (89%), clumsy gait (82%), difficulty eating solid foods (78%) and recurrent respiratory tract infections (72%) were most common in these patients. Symptoms mostly co-occurred and frequently had a fluctuating character, aggravated by infections or fatigue. CONCLUSION: Early referral to diagnose CMS is crucial to enable timely initiation of treatment. Heightened attention to a combination of symptoms related to muscle weakness, rather than individual symptoms, should support paediatricians in flagging these neuromuscular disorders. Medical history taking should be tailored to parents' perceptions, asking questions about recognisable symptoms of muscle weakness.

Repeated onabotulinum neurotoxin A injections for drooling in children with neurodisability.

AIM: To evaluate the effect of repeated onabotulinum neurotoxin A injections for the treatment of drooling in children with neurodisabilities. METHOD: This was a retrospective cohort study, in which the first, second, and third onabotulinum neurotoxin A injection were compared within children treated between 2000 and 2020. Primary outcomes included drooling quotient, visual analogue scale (VAS), and treatment success defined as ≥50% reduction in drooling quotient and/or VAS 8 weeks after treatment. Each outcome was obtained at baseline and 8 weeks posttreatment. RESULTS: Seventy-seven children were included (mean age at first injection: 8y 3mo, SD 3y 7mo, range 3-17y; 44 males, 33 females; 51.9% with cerebral palsy, 45.5% wheelchair-bound). The objective (drooling quotient) and subjective (VAS) effect after the second injection was lower compared to the first injection. The third injection showed less objective and significantly less subjective effect compared to the first injection. An overall success rate of 74.0%, 41.6%, and 45.8% were found for the first, second, and third injection respectively. INTERPRETATION: Although onabotulinum neurotoxin A remained effective throughout the entire treatment course, there is less effect of subsequent onabotulinum neurotoxin A injections compared to the first. Although there might be a loss of effect after repeated injections, there is continued improvement for most children. What this paper adds Repeated injections show a diminished treatment effect after the second injection. A continued improvement is seen in most patients.

Nonadherence to inhaled corticosteroids: A characteristic of the pediatric obese-asthma phenotype?

BACKGROUND: Children with excess weight and asthma tend to respond less well to inhaled corticosteroids (ICS) than children with normal weight, potentially resulting in nonadherence to ICS. OBJECTIVES: To assess whether excess weight (body mass index ≥85th percentile) was associated with general, unintentional, and intentional nonadherence to ICS in children with asthma. METHODS: We analyzed data from 566 children aged 4-13 years with asthma, who used ICS as maintenance therapy, from the cross-sectional Pharmacogenetics of Asthma medication in Children: Medication with Anti-inflammatory effects study. General nonadherence was measured objectively with the proportion of days covered (<50%) and subjectively with the parent-reported Medication Adherence Rating Scale (MARS <21) reflecting parent-reported nonadherent behavior. Unintentional and intentional nonadherence were defined as forgetting to take medication and deliberately changing or skipping doses, respectively, from specific items of the MARS. We performed logistic regression analyses, stratifying estimates by asthma severity and age group. RESULTS: Excess weight was associated with a trend towards increased odds of parent-reported nonadherent behavior (odds ratio [OR]: 1.54; 95% confidence interval [CI]: 0.84-2.81) and objectively measured general nonadherence, but only in moderate-to-severe asthma (OR: 1.71; 95% CI: 0.84-3.48). The odds of intentional, but not unintentional, nonadherence seemed to be greater in children with excess weight than normal weight (OR: 1.94; 95% CI: 0.94-4.01), and the association appeared to be stronger in younger (OR: 2.17; 95% CI 1.00-4.73) versus older children (OR: 1.18; 95% CI: 0.36-3.94). CONCLUSIONS: Excess weight was associated with general nonadherence to ICS, but only in children with moderate-to-severe asthma, and nonadherent behavior, which seemed to be intentional.

External Validation of Model-Based Dosing Guidelines for Vancomycin, Gentamicin, and Tobramycin in Critically Ill Neonates and Children: A Pragmatic Two-Center Study.

BACKGROUND: The Dutch Pediatric Formulary (DPF) increasingly bases its guidelines on model-based dosing simulations from pharmacokinetic studies. This resulted in nationwide dose changes for vancomycin, gentamicin, and tobramycin in 2015. OBJECTIVE: We aimed to evaluate target attainment of these altered, model-based doses in critically ill neonates and children. METHODS: This was a retrospective cohort study in neonatal intensive care unit (NICU) and pediatric ICU (PICU) patients receiving vancomycin, gentamicin, or tobramycin between January 2015 and March 2017 in two university hospitals. The first therapeutic drug monitoring concentration for each patient was collected, as was clinical and dosing information. Vancomycin and tobramycin target trough concentrations were 10-15 and ≤ 1 mg/L, respectively. Target gentamicin trough and peak concentrations were < 1 and 8-12 mg/L, respectively. RESULTS: In total, 482 patients were included (vancomycin [PICU] n = 62, [NICU] n = 102; gentamicin [NICU] n = 97; tobramycin [NICU] n = 221). Overall, median trough concentrations were within the target range for all cohorts but showed large interindividual variability, causing nontarget attainment. Trough concentrations were outside the target range in 66.1%, 60.8%, 14.7%, and 23.1% of patients in these four cohorts, respectively. Gentamicin peak concentrations were outside the range in 69% of NICU patients (term neonates 87.1%, preterm infants 57.1%). Higher creatinine concentrations were associated with higher vancomycin and tobramycin trough concentrations. CONCLUSION: This study illustrates the need to validate model-based dosing advice in the real-world setting as both sub- and supratherapeutic concentrations of vancomycin, gentamicin, and tobramycin were very prevalent. Our data underline the necessity for further individualization by addressing the high interindividual variability to improve target attainment.