Dexmedetomidine at Home for Intractable Dystonia and Insomnia in Children With Special Needs: A Case Series.

BACKGROUND: We know that syndromic conditions and severe chronic diseases can be associated with symptoms that may interfere with sleep, significantly impacting the life quality of children and caregivers. Drugs commonly used in treating insomnia, such as melatonin, benzodiazepines, niaprazine, and antihistamines, are often either ineffective or associated with adverse effects, requiring new therapeutic perspectives. Dexmedetomidine is a selective alpha-2 agonist with hypnotic and anxiolytic effects, which, by stimulating alpha-2 adrenergic receptors in the locus coeruleus, induces sleep comparable to stages 2-3 of the non-REM phase without substantially affecting the respiratory drive during sedation. Its use has already been extensively described in pediatric intensive care or procedural sedation literature. In 2018, the Italian Medicines Agency (Agenzia Italiana Del Farmaco AIFA) authorized the off-label use of dexmedetomidine outside of intensive care in Children undergoing palliative treatment to control distressing symptoms related to pathology and refractory sleep disorders, and the literature reported cases of children who received dexmedetomidine at home. OBJECTIVE: Our study aims to describe the home use of dexmedetomidine in children with insomnia or intractable dystonic states. MEASURES: We conducted a retrospective analysis through a questionnaire addressed to 12 Italian pediatric palliative care centers regarding the home use of dexmedetomidine in sleep disorders and intractable dystonic states. INTERVENTION: We collected a case series of 9 children treated with dexmedetomidine at home, 8 via intranasal and 1 via intravenous route. All children received the first drug administration in the hospital or hospice during a dedicated admission, under close monitoring of vital signs parameters for 72 hours (3 days, range 2-7 days). After discharge, the potential side effects of the drug were explained to the patient's families, and, once informed consent was obtained, the home administration of dexmedetomidine continued, with follow-up by the palliative care team. At home, dexmedetomidine was administered for 3000 days (minimum 1 month, maximum 36 months). The first patient was treated for 1095 days, from 2019 to 2021 (discontinued due to underlying condition-related death). OUTCOMES: All patients observed a persistent benefit from the treatment on symptoms, and none of them discontinued dexmedetomidine administration due to drug-related adverse effects or perceived lack of therapeutic efficacy. CONCLUSIONS: Therefore, its use at home may represent a promising therapeutic approach for intractable sleep disorders or dystonic states in pediatric palliative care children. Further studies are needed to confirm our results.

The use of medical cannabis in pediatric palliative care: a case series.

BACKGROUND: Medical cannabis may be a useful tool for managing treatment-resistant epilepsy and chronic pain, which affect many patients in pediatric palliative care (PPC); however, little evidence is available in this setting. CASE PRESENTATION: We aimed to describe a clinical experience in a setting where high-level evidence may not be obtained. We report our clinical experience in a pediatric palliative care department in Italy. Caregivers reported changes in intensity and frequency of pain and epilepsy events. Six patients received a titrated plant extract of cannabis sativa for 1 year. Only mild and transient adverse events occurred: drowsiness, euphoria, restlessness and tachycardia; the resolution was either spontaneous or obtained by modifying the administration schedule. Treatment was never discontinued. No overdoses occurred. All patients experienced seizures during the pre-treatment observation period, and obtained a reduction in seizure frequency, although with variable extent while receiving cannabis. In addition, a benefit on pain was observed, based on the caregiver's evaluation, and a reduction of analgesic use. CONCLUSION: Our experience suggests that a titrated plant extract preparation of medical cannabis may be useful to control treatment-resistant pain and epilepsy in PPC patients.

Do we always need to treat patients with spinal muscular atrophy? A personal view and experience.

BACKGROUND: We report the clinical outcomes observed in our patients with SMA type 1 or 2 receiving nusinersen, and we comment on the ethical implications of this treatment, in line with our results and those reported by Audic et al. in their analysis published in the Orphanet Journal of Rare Diseases. METHODS: We analyzed records of all children with a genetically diagnosed SMA and clinically confirmed diagnosis of SMA Type 1 or 2 to whom nusinersen was offered. Follow-up lasted 30 months. RESULTS: Among the 17 children with SMA type 1, 6 interrupted treatment with nusinersen due to adverse events or lack of efficacy. Of the remaining 11 patients, 9 are responding to therapy, though multidisciplinary complex care is still required. All those children started nusinersen at a very early age. Eighteen patients with SMA type 2 received nusinersen; five required treatment interruption. The other 13 patients are still on nusinersen therapy, and 6 are responders. Among the seven non-responders, only two met the inclusion criteria of the pivotal trial. CONCLUSIONS: Our analysis further supports the findings reported in the study by Audic et al. We believe that a wider use of nusinersen in clinical practice would require a comprehensive assessment of its actual benefits weighed against the discomfort caused to patients, as well as the identification of the patients who may obtain the best benefits from this treatment.

Effect of a short training on neonatal face-mask ventilation performance in a low resource setting.

BACKGROUND: We assessed whether a short training, effective in a high resource country, was able to improve the quality of face-mask ventilation (FMV) in a low resource setting. METHODS: Local healthcare providers at the Centre Médico-Social, Kouvè, Togo were asked to ventilate a neonatal leak-free manikin before (time-t1) and after (t2) a two-minute training session. Immediately after this section, a further two-minute training with participants aware of the data monitor was offered. Finally, a third 1-minute FMV round (t3) was performed by each participant. Ventilatory parameters were recorded using a computerized system. Primary outcome was the percentage of breaths with relevant mask leak (>25%). Secondary outcomes were percentages of breaths with a low peak inspiratory pressure (PIP<20 cm H2O), within the recommended PIP (20-35 cm H2O) and with a high PIP (>35 cm H2O). RESULTS: Twenty-six subjects participated in the study. The percentage of relevant mask leak significantly decreased (p<0.0001; ß = -0.76, SE = 0.10) from 89.7% (SD 21.5%) at t1 to 45.4% (SD 27.2%) at t2 and to 18.3% (SD 20.1%) at t3. The percentage of breaths within the recommended PIP significantly increased (p<0.0001; ß = +0.54, SE = 0.12). The percentage of breaths with PIP>35 cm H2O was 19.5% (SD 32.8%) at t1 and 39.2% (SD 37.7%) at t2 (padj = 0.27; ß = +0.61, SE = 0.36) and significantly decreased (padj = 0.01; ß = -1.61, SE = 0.55) to 6.0% (SD 15.4%) at t3. CONCLUSIONS: A 2-minute training on FMV, effective in a high resource country, had a positive effect also in a low resource setting. FMV performance further improved after an extra 2-minute verbal recall plus real time feedback. Although the training was extended, it still does not cost much time and effort. Further studies are needed to establish if these basic skills are transferred in real patients and if they are maintained over time.

Use of Zoledronic Acid in Paediatric Craniofacial Fibrous Dysplasia.

We describe a case of a paediatric patient affected by mandibular fibrous dysplasia (FD) with severe and chronic pain who was successfully treated with zoledronic acid (ZOL): a third-generation bisphosphonate. Further research is needed to assess its safety and efficacy as a treatment option for FD in the paediatric population.