Challenges in establishing optimal pediatric palliative care at the university hospital in Slovenia.

The integration of pediatric palliative care (PPC) should become a standard of care for all children with life-limiting and life-threatening illnesses. There are many barriers and misperceptions in pediatrics which hinder the early implementation of PPC. The aim of the study was to design starting points for the establishment of accessible PPC with early involvement of patients in a tertiary-level children's hospital. An intervention, presentation, and discussion on PPC were offered by the hospital PPC team to all employees in the hospital. A total of 237 participants (physicians 30.4%, nurses 49.4%, psychologists 8.4%, and others) completed a questionnaire before and after the intervention. The personnel's knowledge, self-assessment of their ability to perform PPC, attitude to participate in PPC, and their awareness and understanding of the need for PPC were evaluated. The results were analyzed using Pandas and SciPy libraries in Python. The knowledge, awareness, and attitude of the physicians, nurses, and other professionals improved significantly after the intervention. However, the self-assessment of their ability to perform PPC did not increase. Previous experience with the death of a patient has proven to be a stimulus for self-initiative in acquiring knowledge in PPC and was linked with a better attitude and higher awareness of the need for PPC.Conclusions: More education and practical work tailored to the different professional profiles are needed, with adjustments for specific subspecialist areas, especially where patients could be included in early PPC. Although additional studies are needed, we identified the main directions for the further implementation of PPC in clinical practice in our setting.

Clinical and Radiological Characteristics of Non-Benign Pineal Cyst Lesions in Children.

Background: With the increasing availability and advances in brain imaging, pineal cyst lesions (PCL) are becoming a common finding in the pediatric population. In the absence of evidence-based guidelines, optimal diagnostic and therapeutic approaches have not been established, and there is a risk of under- or overtreatment of these patients. Objectives: The aim of our study was to evaluate the clinical presentation and radiological features of PCL in a cohort of pediatric patients and to identify clinical parameters more commonly associated with neoplasms in the pineal region. In addition, the prevalence of PCL in the pediatric population of Slovenia was estimated. Methods: In this observational, cohort study, children treated at University Children's Hospital, Ljubljana, Slovenia in the period 1997-2016 were included if PCL was found on brain imaging. We analyzed indications for referral to a neurologist, clinical signs and symptoms, radiological features, treatment and outcome. Results: The cohort consisted of 143 children with PCL. Pineocytoma was suspected in 31 children (21.7%). Six children underwent surgery - pineocytoma was confirmed in two cases and germinoma in one (2/3 of these children had signs of increased intracranial pressure (ICP), while PCL was benign in the remaining 4 cases. Only 2 PCL enlarged during the study period, both <2mm, none of these children developed neoplasm. Two children had PCL >20mm in diameter; both showed signs of increased ICP, one patient was found to have a germinoma of the pineal region, while the other had no neoplasm. Conclusions: Most PCL do not change their features during radiological follow-up and even atypical PCL are very rarely associated with a malignant neoplasm of the pineal region. A PCL larger than 20 mm and signs of increased ICP were identified as potential markers for selecting patients at risk.

Adaptive skills and mental health in children and adolescents with neuromuscular diseases.

BACKGROUND: Adaptive skills represent the ways that children and adolescents meet their basic needs for self-care, decision making, communication, and learning in their daily life. Having a neuromuscular disease (NMD) not only presents mental health issues, but also impacts these skills. AIMS: Our study aimed to compare the adaptive skills and mental health of paediatric patients with the most common NMDs with their healthy peers and assess how NMDs shape the way patients form relationships with others, engage in leisure activities and take care of their daily living needs. METHODS: We used the Adaptive Behaviour Assessment System (ABAS-3) and Achenbach Child Behaviour Checklist (CBCL) to compare the adaptive skills and mental health symptoms of 50 NMD patients to a demographically-matched control group of 298 peers. We examined specific outcomes of having myotonic dystrophy (DM), Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), spinal muscular atrophy (SMA) or a mixed group of other NMDs. RESULTS: All NMD patients displayed poor practical adaptive skills. When the disease was more likely to involve the central nervous system (DM, DMD) they also showed additional deficits in their conceptual and social skills. Contrary to previous research no increased rate of psychopathological symptoms was found in NMD patients, with the exception of difficulties in the social domain among patients with DM. CONCLUSIONS: Although most children with NMDs displayed more limited practical skills, the specific profile of adaptive skills for each patient group needs to be taken into consideration when planning school support and other psychosocial interventions.

Children and young adults with spinal muscular atrophy treated with nusinersen.

INTRODUCTION: Treatment of children with spinal muscular atrophy (SMA) now includes disease modifying drugs such as nusinersen. Real-world data can provide new insight on the efficacy and safety of nusinersen for treatment of children with SMA. AIM: The aim of our study is to evaluate the effect of treatment of children and young adults with SMA type I, II and III at various stages of the disease after 14 months of treatment with nusinersen. METHODS: In this prospective, two-center (in Slovenia and Czech Republic) study, data from all patients with a genetically confirmed diagnosis of SMA before 19 years of age who were treated with nusinersen were collected before initiation of treatment, and after 6 and 14 months of treatment. Various standardized motor scales and a questionnaire that focused on daily-life activities were used. RESULTS: Form both centers, 61 patients from 2 months to 19 years of age were enrolled in the study. Sixteen had SMA type I (median age 5.2 years); 32 had SMA type II (median age 8.9 years); and 13 had SMA type III (median age 8.6 years). Patients had 2-4 copies of the SMN2 gene. One patient died in the study period and one discontinued treatment. After 14 months of treatment, SMA type I (p = 0.002) and type II (p = 0.002) patients had significantly better outcomes, while type III patients showed a trend towards improvement (p = 0.051) on motor scales. Younger age at the initiation of treatment and a higher number of SMN2 copies is related to a better outcome. Younger children also seem to improve faster compared to older children. No serious side effects were reported. CONCLUSION: The results of our study which included patients of various SMA types and stages of the disease suggest that treatment with nusinersen benefits patients, regardless of SMA type. Earlier age at the initiation of treatment and a higher number of SMN2 copies were related to a better outcome, however even some patients of higher age and/or later stage of the disease benefited from the treatment. Our study also suggests that nusinersen is safe to use, as no major side effects, requiring discontinuation of treatment, were reported. There is an unmet need for novel standardized tests and biomarkers, which could help guide clinician's decisions on the selection of best treatment options and monitor treatment success.

Prevalence and genetic subtypes of congenital myasthenic syndromes in the pediatric population of Slovenia.

AIM: Congenital myasthenic syndromes (CMS) are rare, genetically and phenotypically diverse disorders of neuromuscular transmission. Data on prevalence among children are scarce. Whole exome sequencing facilitated discovery of novel CMS mutations and enabled targeted treatment. Our aim was to identify the prevalence, genetic subtypes and clinical characteristics of CMS in pediatric population of Slovenia. METHODS: In this observational, national, cross-sectional study, medical records were retrospectively reviewed. Children with genetically confirmed CMS, referred over a 19 - year period (2000-2018) to the University Medical Centre, Ljubljana, Slovenia, were included in the study. Genetic and phenotypic characteristics were collected and prevalence of CMS in children was calculated. RESULTS: Eight children with a confirmed genetic mutation in 5 different genes (CHRNE, CHRND, RAPSN, CHAT, MUSK) causative of the CMS were identified. Calculated prevalence of genetically confirmed CMS was 22.2 cases per 1.000.000 children at the end of 2018. INTERPRETATION: The prevalence of genetically confirmed CMS in Slovenian children at the end of 2018 exceeds previously reported prevalence by more than two-fold, which suggests that prevalence in the literature is likely to be underestimated. Two extremely rarely detected mutations in MUSK and CHRND gene were detected and patient's clinical descriptions add important information on genotype-phenotype correlation.