European Achondroplasia Forum Practical Considerations for Following Adults with Achondroplasia.

Achondroplasia is a lifelong condition requiring lifelong management. There is consensus that infants and children with achondroplasia should be managed by a multidisciplinary team experienced in the condition. However, many people are lost to follow-up after the transition from paediatric to adult care, and there is no standardised approach for management in adults, despite the recent availability of international consensus guidelines. To address this, the European Achondroplasia Forum has developed a patient-held checklist to support adults with achondroplasia in managing their health. The checklist highlights key symptoms of spinal stenosis and obstructive sleep apnoea, both among the most frequent and potentially severe medical complications in adults with achondroplasia. The checklist acts as a framework to support individuals and their primary care provider in completing a routine review. General advice on issues such as blood pressure, pain, hearing, weight, adaptive aids, and psychosocial aspects are also included. The checklist provides key symptoms to be aware of, in addition to action points so that people can approach their primary care provider and be directed to the appropriate specialist, if needed. Additionally, the European Achondroplasia Forum offers some ideas on implementing the checklist during the transition from paediatric to adult care, thus ensuring the existing multidisciplinary team model in place during childhood can support in engaging individuals and empowering them to take responsibility for their own care as they move into adulthood.

Assessment of obstructive sleep apnoea in children: What are the challenges we face?

There is an increasing demand for the assessment of sleep-disordered breathing in children of all ages to prevent the deleterious neurocognitive and behaviour consequences of the under-diagnosis and under-treatment of obstructive sleep apnoea [OSA]. OSA can be considered in three broad categories based on predominating contributory features: OSA type 1 [enlarged tonsils and adenoids], type II [Obesity] and type III [craniofacial abnormalities, syndromal, storage diseases and neuromuscular conditions]. The reality is that sleep questionnaires or calculations of body mass index in isolation are poorly predictive of OSA in individuals. Globally, the access to testing in tertiary referral centres is comprehensively overwhelmed by the demand and financial cost. This has prompted the need for better awareness and focussed history taking, matched with simpler tools with acceptable accuracy used in the setting of likely OSA. Consequently, we present key indications for polysomnography and present scalable, existing alternatives for assessment of OSA in the hospital or home setting, using polygraphy, oximetry or contactless sleep monitoring.

Invasive versus non-invasive paediatric home mechanical ventilation: review of the international evolution over the past 24 years.

BACKGROUND: Home mechanical ventilation (HMV) is the treatment for chronic hypercapnic alveolar hypoventilation. The proportion and evolution of paediatric invasive (IMV) and non-invasive (NIV) HMV across the world is unknown, as well as the disorders and age of children using HMV. METHODS: Search of Medline/PubMed for publications of paediatric surveys on HMV from 2000 to 2023. RESULTS: Data from 32 international reports, representing 8815 children (59% boys) using HMV, were analysed. A substantial number of children had neuromuscular disorders (NMD; 37%), followed by cardiorespiratory (Cardio-Resp; 16%), central nervous system (CNS; 16%), upper airway (UA; 13%), other disorders (Others; 10%), central hypoventilation (4%), thoracic (3%) and genetic/congenital disorders (Gen/Cong; 1%). Mean age±SD (range) at HMV initiation was 6.7±3.7 (0.5-14.7) years. Age distribution was bimodal, with two peaks around 1-2 and 14-15 years. The number and proportion of children using NIV was significantly greater than that of children using IMV (n=6362 vs 2453, p=0.03; 72% vs 28%, p=0.048), with wide variations among countries, studies and disorders. NIV was used preferentially in the preponderance of children affected by UA, Gen/Cong, Thoracic, NMD and Cardio-Resp disorders. Children with NMD still receiving primary invasive HMV were mainly type I spinal muscular atrophy (SMA). Mean age±SD at initiation of IMV and NIV was 3.3±3.3 and 8.2±4.4 years (p<0.01), respectively. The rate of children receiving additional daytime HMV was higher with IMV as compared with NIV (69% vs 10%, p<0.001). The evolution of paediatric HMV over the last two decades consists of a growing number of children using HMV, in parallel to an increasing use of NIV in recent years (2020-2023). There is no clear trend in the profile of children over time (age at HMV). However, an increasing number of patients requiring HMV were observed in the Gen/Cong, CNS and Others groups. Finally, the estimated prevalence of paediatric HMV was calculated at 7.4/100 000 children. CONCLUSIONS: Patients with NMD represent the largest group of children using HMV. NIV is increasingly favoured in recent years, but IMV is still a prevalent intervention in young children, particularly in countries indicating less experience with NIV.

Accuracy of tidal volume delivery by paediatric intensive care ventilators: A bench-model study.

BACKGROUND: Tidal volume (Vt) delivery during mechanical ventilation is influenced by gas compression, humidity, and temperature. OBJECTIVES: This bench study aimed at assessing the accuracy of Vt delivery by paediatric intensive care ventilators according to the humidification system. Secondary objectives were to assess the following: (i) the accuracy of Vt delivery in ventilators with an integrated Y-piece pneumotachograph and (ii) the ability of ventilators to deliver and maintain a preset positive end-expiratory pressure. METHODS: Six latest-generation intensive care ventilators equipped with a paediatric mode were tested on the ASL5000 test lung in four simulated paediatric bench models (full-term neonate, infant, preschool-age chile, and school-age child), under volume-controlled mode with a heated humidifier (HH) or a heat moisture exchanger, with various loading conditions. Three ventilators equipped with a Y-piece pneumotachograph were tested with or without the pneumotachograph in the neonatal and infant models. "Accurate Vt" delivery was defined as a volume error (percentage of the preset Vt under body temperature and pressure and saturated water vapour conditions) being ≤10 % of the absolute preset value. RESULTS: Vt accuracy varied significantly across ventilators but was acceptable in almost all the ventilators and all the models, except the neonatal model. The humidification system had an impact on Vt delivery in the majority of the tested conditions (p < 0.05). The use of an HH was associated with a better Vt accuracy in four ventilators (V500, V800, R860, and ServoU) and allowed to achieve an acceptable level of volume error in the neonatal model as compared to the use of heat moisture exchanger. The use of an integrated pneumotachograph was associated with lower volume error in only one ventilator (p < 0.01). All the tested ventilators were able to maintain adequate positive end-expiratory pressure levels. CONCLUSION: The humidification system affects Vt accuracy of paediatric intensive care ventilators, especially in the youngest patients for whom the HH should be preferred.

Positive end-expiratory pressure in chronic care of children with obstructive sleep apnoea.

Positive end-expiratory pressure (PEEP) consists of the delivery of a constant positive pressure in the airways by means of a noninvasive interface aiming to maintain airway patency throughout the entire respiratory cycle. PEEP is increasingly used in the chronic care of children with anatomical or functional abnormalities of the upper airways to correct severe persistent obstructive sleep apnea despite optimal management which commonly includes adenotonsillectomy in young children. PEEP may be used at any age, due to improvements in equipment and interfaces. Criteria for CPAP/NIV initiation, optimal setting, follow-up and monitoring, as well as weaning criteria have been established by international experts, but validated criteria are lacking. As chronic PEEP is a highly specialised treatment, patients should be managed by an expert pediatric multidisciplinary team.

Developmental outcome of children with Robin sequence treated with the current Paris protocol.

AIM: We aimed to investigate the developmental outcome of children with Robin sequence (RS) for whom continuous positive airway pressure was the main strategy to release upper airway obstruction. METHODS: We included children with isolated RS or RS associated with Stickler syndrome who were aged 15 months to 6 years. We used the French version of the Child Development Inventory and calculated the developmental quotient (DQ) for eight different domains and the global DQ (DQ-global). We searched for determinants of risk of delay. RESULTS: Of the 87 children, for 71%, the developmental evolution was within the norm (DQ-global ≥86 or ≥-1 SD), 29% were at high risk of delay (DQ-global <86 or <-1 SD), and only 3% were at very high risk of delay (DQ-global <70 or <-2 SD). The DQs for expressive language and language comprehension were lower in our study population than the general population, but an improvement was noticed with the children's growth. CONCLUSION: Risk of a developmental delay was not greater for children with the most severe respiratory phenotype than the others. Children whose mothers had low education levels were more at risk than the others.

Effect of long term noninvasive ventilation in children on parent's quality of life.

OBJECTIVE: Improving or maintaining the quality of life of the family of children treated with long term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) is a major concern; but studies are scarce. The aim of the study was to evaluate the impact of long term CPAP or NIV in children on anxiety, depression, quality of sleep, and quality of life of their parents. METHODS: Validated questionnaires evaluating anxiety and depression (hospital anxiety and depression scale), sleep quality (Pittsburgh sleep quality index), daytime sleepiness (Epworth sleepiness scale), and parents' quality of life (PedsQL family impact module) were completed by parents of children who were started on CPAP/NIV before (M0) and after 6-9 months (M6) of treatment. RESULTS: The questionnaires of 36 parents (30 mothers, 6 fathers) of 31 children were analyzed. For the entire group, no significant change was observed in anxiety, depression, sleep quality, daytime sleepiness, and quality of life between M0 and M6. When analyzing questionnaire class changes between M0 and M6: anxiety was relieved in 23% of parents and worsened in 29%, depression was relieved in 14% and worsened in 20%, sleep quality improved in 43% and worsened in 27%, sleepiness improved in 26% and worsened in 17%, with no change in the other parents. CONCLUSION: Long term CPAP/NIV in children had no significant effect on parents' anxiety, depression, sleep quality, and quality of life.

What defines a great surgeon? A survey study confronting perspectives.

Background: The definition of a great surgeon is usually reported by surgeons themselves. The objective of the study was to define a multifaceted definition of a great surgeon, by confronting patients', healthcare workers', and surgeons' perspectives. Study design: An online open-ended questionnaire was created to identify three qualities and three shortcomings defining a great surgeon. Age, gender, and profession of respondents were collected. Responses with a similar meaning were combined into word groups and labeled within four themes: human qualities, technical surgical skills (TSS), non-technical skills (NTS), and knowledge. Multivariate analyses were conducted between themes and respondent characteristics. Results: Four thousand seven hundred and sixty qualities and 4,374 shortcomings were obtained from 1,620 respondents including 385 surgeons, 291 patients, 565 operating theater (OT) health professionals, and 379 non-OT health professionals. The main three qualities were dexterity (54% of respondents), meticulousness (18%), and empathy (18%). There was no significant difference between professional categories for TSS. Compared with surgeons, non-OT health professionals and patients put more emphasis on human qualities (29 vs. 39% and 42%, respectively, p < .001). OT health professionals referred more to NTS than surgeons (35 vs. 22%, p < 0.001). Knowledge was more important for surgeons (19%) than for all other professional categories (p < 0.001). Conclusions: This survey illustrates the multifaceted definition of a great surgeon. Even if dexterity is a major quality, human qualities are of paramount importance. Knowledge seems to be underestimated by non-surgeons, although it essential to understand the disease and preparing the patient and OT team for the procedure.

Motor outcomes in patients with infantile and juvenile Pompe disease: Lessons from neurophysiological findings.

In Infantile Onset Pompe Disease (IOPD), enzyme replacement therapy (ERT) may improve survival, cardiac function, and motor development. However, even with early enzyme replacement therapy, some patients experienced poor response to ERT and abnormal motor milestones that could be due to motor neuron involvement. In this long-term retrospective study, we analyzed concomitant clinical motor outcomes and electroneuromyography (ENMG) findings in patients with IOPD and Juvenile Onset Pompe Disease (JOPD). Twenty-nine pediatric patients were included and 20 surviving were analyzed for neuromotor studies: 12 had IOPD (group 1), 4 had JOPD (group 2) and 4 (group 3) received ERT in the first month of age. Motor nerve conduction studies were mostly normal. Needle EMG performed at diagnosis always indicated the existence of myopathy that responded to ERT. Two IOPD patients (group 1) presenting with mixed motor neuropathy and myopathy displayed a poor outcome and never walked. Two patients became non-walkers (one IOPD patient and one patient of group 3) at respectively 9 and 3 years of age. One JOPD patient is about to lose walking ability. This motor deterioration was associated with the development of a motor neuropathy. Patients older than 10 years of age develop a motor neuropathy. Initial or secondary motor neuron involvement seems to be associated with a poor motor outcome showing that ERT may fail to prevent the accumulation of glycogen in motor neuron. Neurophysiological findings are important to assess severity of motor neuron damage in all Pompe pediatric patients and should be systematically performed.

Limitations of the apnea-hypopnea index in children and young adults with neuromuscular disorders.

There are no validated criteria to initiate noninvasive ventilation (NIV) in children and young adults with neuromuscular disease (NMD). In order to analyze NIV initiation criteria, we reviewed the polysomnography (PSG) criteria that led to the initiation of NIV in 61 consecutive patients with NMD, median age 4.1 (0.8-21) years, who had a PSG during their routine care. NIV was initiated on abnormal PSG data (apnea-hypopnea index (AHI) > 10 events/h and/or a transcutaneous carbon dioxide pressure > 50 mmHg and/or a pulse oximetry 〈 90%, both during at least 2% sleep time or 〉 5 consecutive minutes) in 11 (18%) patients. Six of these 11 patients had an AHI ≤ 10 events/h and would not have been ventilated if only AHI was retained. However, one of these 6 patients had isolated nocturnal hypoxemia, 3 isolated nocturnal hypercapnia and 2 abnormal respiratory events. Six (10%) patients with a normal PSG were started on NIV on clinical criteria. Our results show the limitation of the AHI when taken as the unique PSG criterion for NIV initiation in young patients with NMD and underline the need to include also abnormalities of overnight gas exchange into the NIV decision-making process.

Detection of Simulated Pediatric Breathing by CPAP/Noninvasive Ventilation Devices.

BACKGROUND: Home CPAP and noninvasive ventilation (NIV) are increasingly used in children. An appropriate choice of the CPAP/NIV device, according to the manufacturer recommendations, should guarantee accurate data collection software. However, not all devices display accurate patient data. We hypothesized that the detection of patient breathing may be expressed as a minimal tidal volume (VTmin ) rather than a minimal weight. The aim of the study was to estimate the VTmin detected by home ventilators when set on CPAP. METHODS: Twelve level I-III devices were analyzed using a bench test. Pediatric profiles were simulated with increasing VT values to determine the VTmin that the ventilator may detect. The duration of CPAP use and the presence/absence of waveform tracings on the built-in software were also gathered. RESULTS: VTmin varied according to the device, ranging from 16-84 mL, independent of level category. The duration of CPAP use was underestimated in all level I devices, which were either not able to display any waveform or only intermittently, until VTmin was reached. The duration of CPAP use was overestimated for the level II and III devices, with the display of different waveforms according to the device as soon as the device was switched on. CONCLUSIONS: Based on the VTmin detected, some level I and II devices may be suitable for infants. A careful testing of the device should be done at CPAP initiation, with a review of data generated from ventilator software.

Respiratory effort during noninvasive positive pressure ventilation and continuous positive airway pressure in severe acute viral bronchiolitis.

OBJECTIVES: To assess if noninvasive positive pressure ventilation (NIPPV) is associated with a greater reduction in respiratory effort as compared to continuous positive airway pressure (CPAP) during severe acute bronchiolitis, with both supports set either clinically or physiologically. METHODS: Twenty infants (median [IQR] age 1.2 [0.9; 3.2] months) treated <24 h with noninvasive respiratory support (CPAP Clin, set at 7 cmH2 O, or NIPPV Clin) for bronchiolitis were included in a prospective single-center crossover study. Esogastric pressures were measured first with the baseline support, then with the other support. For each support, recordings were performed with the clinical setting and a physiological setting (CPAP Phys and NIPPV Phys), aiming at normalising respiratory effort. Patients were then treated with the optimal support. The primary outcome was the greatest reduction in esophageal pressure-time product (PTPES /min). Other outcomes included improvement of the other components of the respiratory effort. RESULTS: NIPPV Clin and Phys were associated with a lower PTPES /min (164 [105; 202] and 106 [78; 161] cmH2 O s/min, respectively) than CPAP Clin (178 [145; 236] cmH2 O s/min; p = 0.01 and 2 × 10-4 , respectively). NIPPV Clin and Phys were also associated with a significant reduction of all other markers of respiratory effort as compared to CPAP Clin. PTPES /min with NIPPV (Clin or Phys) was not different from PTPES /min with CPAP Phys. There was no significant difference between physiological and clinical settings. CONCLUSION: NIPPV is associated with a significant reduction in respiratory effort as compared to CPAP set at +7 cmH2 O in infants with severe acute bronchiolitis. CPAP Phys performs as well as NIPPV Clin.

Craniofacial growth and function in achondroplasia: a multimodal 3D study on 15 patients.

BACKGROUND: Achondroplasia is the most frequent FGFR3-related chondrodysplasia, leading to rhizomelic dwarfism, craniofacial anomalies, stenosis of the foramen magnum, and sleep apnea. Craniofacial growth and its correlation with obstructive sleep apnea syndrome has not been assessed in achondroplasia. In this study, we provide a multimodal analysis of craniofacial growth and anatomo-functional correlations between craniofacial features and the severity of obstructive sleep apnea syndrome. METHODS: A multimodal study was performed based on a paediatric cohort of 15 achondroplasia patients (mean age, 7.8 ± 3.3 years), including clinical and sleep study data, 2D cephalometrics, and 3D geometric morphometry analyses, based on CT-scans (mean age at CT-scan: patients, 4.9 ± 4.9 years; controls, 3.7 ± 4.2 years). RESULTS: Craniofacial phenotype was characterized by maxillo-zygomatic retrusion, deep nasal root, and prominent forehead. 2D cephalometric studies showed constant maxillo-mandibular retrusion, with excessive vertical dimensions of the lower third of the face, and modifications of cranial base angles. All patients with available CT-scan had premature fusion of skull base synchondroses. 3D morphometric analyses showed more severe craniofacial phenotypes associated with increasing patient age, predominantly regarding the midface-with increased maxillary retrusion in older patients-and the skull base-with closure of the spheno-occipital angle. At the mandibular level, both the corpus and ramus showed shape modifications with age, with shortened anteroposterior mandibular length, as well as ramus and condylar region lengths. We report a significant correlation between the severity of maxillo-mandibular retrusion and obstructive sleep apnea syndrome (p < 0.01). CONCLUSIONS: Our study shows more severe craniofacial phenotypes at older ages, with increased maxillomandibular retrusion, and demonstrates a significant anatomo-functional correlation between the severity of midface and mandible craniofacial features and obstructive sleep apnea syndrome.