Importance of parental involvement in paediatric palliative care in Hong Kong: qualitative case study.

OBJECTIVE: To compare and contrast the perceived care needs of children with life-limiting conditions (CLLC) from the perspectives of the children, parents and healthcare providers. DESIGN: A qualitative case study method using semistructured interviews was employed with a within-case and across-case analysis. Themes and subthemes emerging from the cases were compared and contrasted in the across-case analysis to explore the similarities and variations in participant perceptions. SETTING/PARTICIPANTS: The setting was the paediatric departments of five regional hospitals in Hong Kong. Twenty-five sets of informants (CLLC-parent-healthcare provider) were recruited, with 65 individual interviews conducted. RESULTS: A total of 3784 units of analysis were identified, resulting in three themes with subthemes. 'Living with the disease' (55.8%) occupied the largest proportion, followed by 'information and understanding about the disease' (27.4%), and 'care support and palliative care' (16.8%). Healthcare provider support mainly focused on physical concerns. Family and social support were present, but carer stress created tension between couples. Doctors were the primary source of medical information, but the parents had to seek further information via the internet and support from patient groups. There was a perceived need for better coordination and collaboration of care. The palliative care approach coordinated by nurses was seen as helpful in addressing the care needs of the CLLC. CONCLUSIONS: This original study identified the importance of palliative care with active engagement of parents which can address the service gap for CLLC.

Prevalence and predictors of depressive symptoms among caregivers of patients with epilepsy in Hong Kong.

STUDY AIM: To estimate the prevalence of high caregiving burden and depressive symptoms among caregivers (CG) of patients with epilepsy (PWEs) in Hong Kong and identify risk and protective factors for both outcomes after the Model of Stress and Carer Burden (MSCB). METHODS: This cross-sectional study recruited participants from local epilepsy clinics to complete a 15-minute survey on a tablet. Caregiving burden (CB) was assessed using the 4-item Zarit Caregiver Burden Interview. Depressive symptoms were assessed using the 2-item Patient Health Questionnaire. Family functioning was assessed using the Short-Form Family Assessment Device General Functioning Subscale. Sociodemographic data of the caregivers and clinical data of the PWE they cared for were described. Hierarchical logistic regression models were used to analyze the factors associated with the outcomes. RESULTS: A hundred and fifty-one CGs of PWEs were recruited for this study. The prevalence of high caregiving burden (ZBI-4 > 7) for CGs of PWEs was 58.9% (n = 89), whereas the prevalence of high depressive symptoms (PHQ2 > 2) was 23.8% (n = 36). Hierarchical logistic regression analysis revealed that entering patient characteristics and care situations did not enhance the model's predictability. In the full model, a high perceived CB was a risk factor for elevated depressive symptoms. Good physical health protects against depressive symptoms. CONCLUSIONS: Among caregivers of PWE in Hong Kong, a high perceived caregiving burden was a risk factor for elevated depressive symptoms; however, the clinical characteristics of the PWEs were not. Self-reported physical health is a protective factor against increased depressive symptoms.

Quality of life and symptom burden in children with neurodegenerative diseases: using PedsQL and SProND, a new symptom-based scale.

BACKGROUND: Children with neurodegenerative conditions (CNDC) often suffer from severe neurodisability and high symptom burden with multisystemic involvement. However, their symptom burden and health-related quality of life (HRQOL) is not systematically documented in the literature, and there is no existing tool for such purposes. We designed our own tool for scoring of symptom burden amongst CNDCs and adopted the PedsQL generic score 4.0 to quantify the impact of overall symptom burden on children's overall HRQOL. METHODS: The Symptom Profile for children with neurodegnerative condition (SProND) questionnaire was developed, which consisted of 14 questions grouped according to 5 categories, namely epilepsy, neurobehavioural, movement and mobility related, breathing and swallowing, and other daily activities. CNDCs were recruited during visits to the Comprehensive Neurometabolic / Neurodegenerative Program of the Duchess of Kent Children's Hospital and Hong Kong Children's Hospital between November 2019 and March 2020. The SProND and PedsQL 4.0 Generic Core Scales were distributed to consenting parents of CNDCs. RESULTS: 36 CNDCs were recruited and matched with community controls. The response rate of subject and control were 99.5% and 98.7% respectively. The Cronbach alpha was 0.61 for the neurobehavioural domain and > = 0.7 for other domains. The greater number of symptoms each subject experiences, the worse his/ her PedsQL scores. Subjects displaying hypersalivation and swallowing difficulties had average physical health summary scores of less than 30% compared with subjects without these symptoms. On the other hand, average psychosocial health summary scores of subjects with involuntary movements, joint stiffness, hypersalivation, sleep problem and anorexia were approximately 70% compared to subjects without these symptoms. DISCUSSION AND CONCLUSION: This is one of the first studies to look at CNDCs as a group. We propose the SProND questionnaire for evaluation of symptom profile amongst CNDCs with satisfactory internal and external validity. It demonstrates how physical symptoms impact both physical and psychosocial HRQOL, and the cumulative effect of individual symptoms on the overall HRQOL. As such, CNDCs should be systematically screened for multi-systemic symptoms as a routine part of their clinical care, and care plans should be individually catered to individual patients' symptom burden and specific needs.

Guillain-Barré syndrome in children - High occurrence of Miller Fisher syndrome in East Asian region.

BACKGROUND: Guillain-Barré syndrome (GBS) is a rare acquired immune-mediated polyneuropathy. Updated population-based data concerning paediatric GBS is needed. METHODS: Paediatric patients aged below 18 years diagnosed with GBS between 2009 and 2018 in all 11 paediatric departments in Hong Kong were identified from the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System. The collected data from medical health records were reviewed by paediatric neurologist from each department. Estimated incidence of paediatric GBS was calculated. We also compared our findings with other paediatric GBS studies in Asia. RESULTS: 63 subjects of paediatric GBS were identified, giving an estimated annual incidence of 0.62 per 100,000 population. Half of the subjects had acute inflammatory demyelinating polyneuropathy (AIDP) (n = 31; 49.2%), one quarter had Miller Fisher Syndrome (MFS) (n = 16; 25.4%), one-fifth had axonal types of GBS (n = 12; 19.0%), and four were unclassified. Paediatric subjects with axonal subtypes of GBS compared to the other 2 subtypes, had significantly higher intensive care unit (ICU) admission rates (p = 0.001) and longest length of stay (p = 0.009). With immunomodulating therapy, complete recovery was highest in those with MFS (100%), followed by AIDP (87.1%) and axonal GBS (75%). Our study also confirms a higher MFS rate for paediatric GBS in East Asia region and our study has the highest MFS rate (25.4%). CONCLUSION: Our population-based 10-year paediatric GBS study provides updated evidence on estimated incidence, healthcare burden and motor outcome of each subtype of paediatric GBS and confirmed a higher occurrence of paediatric MFS in East Asia.

Prevalence and healthcare utilization of rare neurological diseases in Hong Kong: 2014-2018.

BACKGROUND: There has been increasing attention focused on the epidemiology of rare diseases (RDs) in recent years. Rare neurological diseases (RNDs) constitute a significant proportion of RDs; however, relevant research is still lacking. METHODS: A list of ICD-10 codes corresponding to RNDs was compiled using adaptations from the Orphanet Classification of Rare Diseases, and classified into rare epilepsy, movement-related, neurocutaneous, neuroimmune, neurometabolic and neurodegenerative, neuromuscular and other RNDs. Using the Clinical Data Analysis and Reporting System, which holds public hospital healthcare records of Hong Kong anonymously, we calculated the prevalence and healthcare utilization of RND patients between 2014 and 2018. The list of RNDs was also used to review relevant pharmacological trials within the International Clinical Trials Registry Platform between 2009 and 2018. RESULTS: The prevalence of RNDs in Hong Kong is 3.6 in 1,000 individuals. Patients with RNDs had frequent emergency department, outpatient and inpatient healthcare utilization. The average annual cost per patient is estimated at HKD 182,075 (€ 19,688). Different categories of RNDs showed different patterns of healthcare utilization. Moreover, there were only 677 RND-related pharmacological trials during the study period, and no trial was found for 78% of RNDs. CONCLUSIONS: This is one of the first population studies on the prevalence and healthcare utilization patterns of RNDs, with comprehensive reviews of RND-related pharmacological research. It shows high healthcare utilization rates among patients with RNDs, as well as a wide research gap in many RNDs. We call for better attention and tailored healthcare for these patients.

Clinical Spectrum and Burden of Influenza-Associated Neurological Complications in Hospitalised Paediatric Patients.

BACKGROUND: Influenza is one of the most common causes of acute respiratory tract infections around the world. Influenza viruses can cause seasonal epidemics. There remains limited information on the impact of both seasonal influenza A and influenza B related hospitalisations from neurological complications in paediatric populations in Asia. OBJECTIVES: To examine both the clinical spectrum and healthcare burden of influenza-associated neurological complications (IANCs) within the paediatric population of Hong Kong. METHODS: We conducted a population-based retrospective study to identify all paediatric patients (<18 years) admitted to a public hospital in Hong Kong with a confirmed influenza A or B infection between 2014 and 2018 using the Clinical Data Analysis and Reporting System of the Hospital Authority. The clinical spectrum of the paediatric patients with IANCs was studied. The clinical burden of paediatric influenza patients with IANCs were compared to paediatric influenza patients without neurological complications. RESULTS: A total of 28,016 children admitted to the paediatric wards diagnosed to have influenza A or B infection were identified, accounting for 5.7% (28,016/489,955) of total paediatric admissions. 67.3% had influenza A and 32.7% had influenza B, and 8.9% had IANCs. The mean annual incidence of IANCs in children was 57 per 100,000 population. The spectrum of IANCs in our paediatric patients included febrile seizures (80.6%), myositis (11.4%), seizures with fever (5.4%), influenza-associated encephalitis/encephalopathy (IAE) (2.6%) and rarely Guillain-Barré syndrome (0.04%). Most paediatric patients with IANCs (85.5%) presented at a young age of <6 years. Paediatric patients with IANCs had significant longer hospital stays (p < 0.001), higher percentages of mechanical ventilation use (p < 0.05) and PICU admissions (p < 0.001), and higher mortality rates (p < 0.001) compared to those without neurological complications. Amongst those with IANCs, IAE was the sole cause of all seven reported mortalities. CONCLUSIONS: Seasonal influenza A & B is a common cause of hospitalisation for paediatric patients in Hong Kong. We found neurological complications from influenza A and B caused a significantly higher clinical burden compared to those without neurological complications. Children in younger age groups (<6 years old) are at highest risk and thus increasing vaccination coverage to this age group is recommended.

Healthcare burden of rare diseases in Hong Kong - adopting ORPHAcodes in ICD-10 based healthcare administrative datasets.

BACKGROUND: The burden of rare diseases is important for healthcare planning but difficult to estimate. This has been facilitated by the development of ORPHAcodes, a comprehensive classification and coding system for rare diseases developed by the international consortium Orphanet, with cross-references to the 10th version of the International Classification of Diseases and Related Health Problems (ICD-10). A recent study in Western Australia made use of this cross-referencing to identify rare diseases-related admissions in health administrative datasets. Such methodology was adopted in Hong Kong, which has a population of 7 million comprising of 92% ethnic Chinese, with over 80% of admissions taking place in the public hospitals and available for review from the local public healthcare database. MAIN BODY: Our objective was to identify the inpatient healthcare burden of rare diseases in Hong Kong. We extracted admission records of all patients coded with one or more of the 1084 ICD-10 codes cross referenced with 467 ORPHAcodes during the study period from 1st January 2005 to 31st December 2016. We further analysed rare disease-related inpatient healthcare cost using a subset of patients admitted during 1st April 2015 - 31st March 2016. A total number of 546,673 admissions were identified, representing 3.2% of total admissions during the study period. By the end of the study, 109,535 patients were alive, representing 1.5% of the overall population. Prevalence of rare diseases was found to be 1 in 67 in the Hong Kong population. The most common rare disease category in the paediatric age group was 'rare developmental defect during embryogenesis'; whereas that amongst adults was 'rare haematologic disease'. The aforementioned subset of patients accounted for 330,091 inpatient-days, placing the estimated total inpatient cost for rare disease population at HKD$1,594,339,530 i.e. 4.3% of total inpatient cost in 2015-2016. CONCLUSION: Cross referencing between ICD-10 and ORPHAcodes may be adopted in different healthcare datasets for international comparison. Despite differences in the prevalence of individual disease, the disparity between rare disease prevalence (1.5%) and associated inpatient cost (4.3%) in Hong Kong reflects the importance of rare diseases in healthcare policies.

Spinal Muscular Atrophy With Respiratory Distress Type 1-A Child With Atypical Presentation.

The authors report a child with spinal muscular atrophy with respiratory distress type 1 (SMARD1). She presented atypically with hypothyroidism and heart failure due to septal defects that required early heart surgery and microcephaly in association with cerebral atrophy and thin corpus collosum. The subsequent asymmetrical onset of diaphragmatic paralysis, persistent hypotonia, and generalized muscle weakness led to the suspicion of spinal muscular atrophy with respiratory distress type 1. Sanger sequencing confirmed a compound heterozygous mutation in the Immunoglobulin Mu Binding Protein 2 (IGHMBP2) gene, with a known mutation c.2362C > T (p.Arg788*) and a novel frameshift mutation c.2048delG (p.Gly683A1afs*50). Serial nerve conduction study and electromyography confirmed progressive sensorimotor polyneuropathy and neuronopathy. In summary, this case report describes a child with spinal muscular atrophy with respiratory distress type 1 also with congenital cardiac disease and endocrine dysfunction, expanding the phenotypic spectrum of this condition. A high index of suspicion is needed in diagnosing this rare condition to guide the management and genetic counseling.

Use of clinical chromosomal microarray in Chinese patients with autism spectrum disorder-implications of a copy number variation involving DPP10.

BACKGROUND: Array comparative genomic hybridization (aCGH) is recommended as a first-tier genetic test for children with autism spectrum disorder (ASD). However, interpretation of results can often be challenging partly due to the fact that copy number variants (CNVs) in non-European ASD patients are not well studied. To address this literature gap, we report the CNV findings in a cohort of Chinese children with ASD. METHODS: DNA samples were obtained from 258 Chinese ASD patients recruited from a child assessment center between January 2011 and August 2014. aCGH was performed using NimbleGen-CGX-135k or Agilent-CGX 60k oligonucleotide array. Results were classified based on existing guidelines and literature. RESULTS: Ten pathogenic CNVs and one likely pathogenic CNV were found in nine patients, with an overall diagnostic yield of 3.5%. A 138 kb duplication involving 3' exons of DPP10 (arr[GRCh37] 2q14.1(116534689_116672358)x3), reported to be associated with ASD, was identified in one patient (0.39%). The same CNV was reported as variant of uncertain significance (VUS) in DECIPHER database. Multiple individuals of typical development carrying a similar duplication were identified among our ancestry-matched control with a frequency of 6/653 (0.92%) as well as from literature and genomic databases. CONCLUSIONS: The DPP10 duplication is likely a benign CNV polymorphism enriched in Southern Chinese with a population frequency of ~1%. This highlights the importance of using ancestry-matched controls in interpretation of aCGH findings.

A novel patient with an attenuated Costello syndrome phenotype due to an HRAS mutation affecting codon 146-Literature review and update.

De novo germline mutations in HRAS cause Costello syndrome, with >95% of the mutations causing Costello syndrome affecting amino acid position 12 (p.Gly12) or 13 (p.Gly13). We report on a patient with de novo missense mutation causing an amino acid change at codon 146 of HRAS, c.436G > C:p.Ala146Pro, who presented with subtle dysmorphic features, failure to thrive, global developmental delay, and hypertrophic obstructive cardiomyopathy. Mutations affecting codon 146 are observed in <1% of patients with Costello syndrome. From literature search, there were only two other patients reported with mutations involving the same location. We summarized and updated their findings, and discussed evidence to show that these patients with less obvious signs of Costello syndrome may not necessarily run a more benign clinical course.