Client Service Receipt Inventory as a standardised tool for measurement of socio-economic costs in the rare genetic disease population (CSRI-Ra)

The measurement of costs is fundamental in healthcare decision-making, but it is often challenging. In particular, standardised methods have not been developed in the rare genetic disease population. A reliable and valid tool is critical for research to be locally meaningful yet internationally comparable. Herein, we sought to develop, contextualise, translate, and validate the Client Service Receipt Inventory for the RAre disease population (CSRI-Ra) to be used in cost-of-illness studies and economic evaluations for healthcare planning. Through expert panel discussions and focus group meetings involving 17 rare disease patients, carers, and healthcare and social care professionals from Hong Kong, we have developed the CSRI-Ra. Rounds of forward and backward translations were performed by bilingual researchers, and face validity and semantic equivalence were achieved through interviews and telephone communications with focus group participants and an additional of 13 healthcare professional and university students. Intra-class correlation coefficient (ICC) was used to assess criterion validity between CSRI-Ra and electronic patient record in a sample of 94 rare disease patients and carers, with overall ICC being 0.69 (95% CI 0.56–0.78), indicating moderate to good agreement. Following rounds of revision in the development, contextualisation, translation, and validation stages, the CSRI-Ra is ready for use in empirical research. The CSRI-Ra provides a sufficiently standardised yet adaptable method for collecting socio-economic data related to rare genetic diseases. This is important for near-term and long-term monitoring of the resource consequences of rare diseases, and it provides a tool for use in economic evaluations in the future, thereby helping to inform planning for efficient and effective healthcare. Adaptation of the CSRI-Ra to other populations would facilitate international research

Evaluating the health-related quality of life of the rare disease population in Hong Kong using EQ-5D 3-level

Objectives This study aimed to establish a normative profile of health-related quality of life (HRQOL) of the rare disease (RD) population in Hong Kong (HK) and identify potential predictors. Methods Between March 2020 and October 2020, patients with RD and caregivers were recruited through Rare Disease Hong Kong, the largest RD patient group alliance in HK. HRQOL was derived using the EQ-5D 3-Level with reference to the established HK value set. Utility scores were stratified according to demographics and disease-related information. Multiple linear regression was performed to explore the associations between patient characteristics and HRQOL. Results A total of 286 patients, covering 107 unique RDs, reported a mean utility score of 0.53 (SD 0.36). Thirty patients (10.5%) reported negative utility scores, indicating worse-than-death health states. More problems were recorded in the “usual activities” and “self-care” dimensions. Univariate analyses revealed that neurologic diseases, high out-of-pocket expenditure, home modification, and living in public housing or subdivided flats/units were significantly associated with lower HRQOL. A total of 99 caregivers reported a mean utility score of 0.78 (SD 0.17), which was significantly associated with the utility score of patients they took care of (r = 0.32; P = .001). Conclusions The normative profile of the RD population was established, which revealed lower HRQOL in the RD population than other chronic disease groups and general population in HK. Findings were corroborated by evidence from other cohorts using EQ-5D, combined as part of a meta-analysis. Identifying predictors highlight areas that should be prioritized to improve HRQOL of RD population through clinical and psychosocial dimensions

The reciprocal relationship between body mass index categories and physical fitness: a 4‐year prospective cohort study of 20 000 Chinese children

Introduction: Body mass index (BMI) categories and physical fitness are associated but the reciprocal relationship between BMI categories and physical fitness has not been investigated. This study aims to investigate the longitudinal reciprocal relationship between BMI categories and physical fitness. Methods: This is a population-based 4-year cohort study in 48 elementary schools. Children aged 6 to 9 years at recruitment were included. BMI categories and physical fitness including handgrip strength, core muscle endurance, flexibility, and cardiorespiratory fitness were measured using standard equipment and protocol. Results: Among 26 392 eligible participants, 19 504 (73.9%) were successfully followed for 3 years. Baseline obesity prevalence was 5.9%. After 3 years, those who were unfit at baseline had an increased risk of obesity (risk ratio [RR] 1.41, 95% CI 1.16-1.71, P < .001) and those who were fit at baseline had a decreased risk of obesity (RR 0.69, 95% CI 0.60-0.80, P < .001) compared with moderately fit children. Furthermore, improvement of fitness predicted decreased risk of obesity. Similarly, normal body weight also predicted better physical fitness. The path analysis confirmed a strong reciprocal relationship between physical fitness and obesity. Conclusions: Better physical fitness was prospectively associated with normal weight and vice versa. Physically fit children were more likely to maintain a healthy weight and those with a healthy weight were more likely to be physically fit, which is important for healthy development

Is respiratory viral infection really an important trigger of asthma exacerbations in children?

We performed a prospective cohort study from September 2003 to December 2004 to delineate attributing the effect of different respiratory viral infections including newly discovered ones to asthma exacerbations in children in Hong Kong. One hundred and fourteen children aged 6–14 years with chronic stable asthma and on regular inhaled steroid were monitored for respiratory symptoms over a full calendar year from recruitment. They would attend the study clinic if peak expiratory flow rate decreased to below 80% of their baselines, if they met a predefined symptom score, or if parents subjectively felt them developing a cold. Virological diagnosis using virus culture, antigen detection, and polymerase chain reaction methods on nasal swab specimens would be attempted for all these visits irrespective of triggers. Physician diagnosed outcome of each episode was documented. Three hundred and five episodes of respiratory illnesses were captured in the cohort. Nasal specimens were available in 166 episodes, 92 of which were diagnosed as asthma exacerbations, and 74 non-asthma related episodes. Respiratory viruses were detected in 61 of 166 episodes (36.7%). There was no significant difference in virus detection rate between asthma exacerbations (32 out of 97 episodes, 34.8%) and non-asthma respiratory illnesses (29 out of 79 episodes, 39.2%). Although newly discovered respiratory viruses were identified in these episodes, rhinovirus was the commonest organism associated with both asthma exacerbations and non-asthma related episodes. Plausible explanations for much lower virus detection rate than previously reported include improved personal hygiene and precautionary measures taken during respiratory tract infections in the immediate post-severe acute respiratory syndrome period together with a significant contribution of other adverse factors like environmental air pollution. We conclude that not all viral infections in children with asthma lead to an asthma exacerbation and the attributing effect of different triggers of asthma exacerbations in children vary across different time periods and across different localities

Age- and sex-specific physical fitness reference and association with body mass index in Hong Kong Chinese schoolchildren

There is lacking a population-based study on the fitness level of Hong Kong schoolchildren, and it seems that increasing childhood obesity prevalence has shifted the classification of healthy fitness, with ‘underfit’ as normal. This cross-sectional territory study aimed to develop an age- and sex-specific physical fitness reference using a representative sample of children aged 6–17 and to determine the associations with body mass index in schoolchildren. The study analyzed Hong Kong School Physical Fitness Award Scheme data covering grade 1 to grade 12 students’ physical fitness and anthropometric measurements from 2017 to 2018. This reference was established without the impact due to COVID-19. Four aspects of physical fitness tests were measured using a standardized protocol, including (i) upper limb muscle strength, (ii) one-minute sit-up, (iii) sit-and-reach, and (iv) endurance run tests. The generalized additive model for location, scale, and shape was used to construct the reference charts. A Mann–Whitney U test was used to compare the mean differences in age, weight, and height, and a Pearson’s chi-square test was used to examine the distributions of sex groups. A Kruskal–Wallis test was used to compare the group differences in BMI status, followed by the Dunn test for pairwise comparisons. A 5% level of significance was regarded as statistically significant. Data of 119,693 students before the COVID-19 pandemic were included in the analysis. The association between physical fitness level and BMI status varied depending on the test used, and there were significant differences in fitness test scores among BMI groups. The mean test scores of the obese group were lower in most of the tests for both boys and girls, except for handgrip strength. The underweight group outperformed the obese group in push-ups, one-minute sit-ups, and endurance run tests, but not in handgrip strength. In conclusion, a sex- and age-specific physical fitness reference value for Hong Kong Chinese children aged 6 to 17 years old is established, and this study demonstrated a nonlinear relationship between BMI status and physical fitness. The reference will help to identify children with poor physical fitness to offer support and guidance on exercise training. It also serves as a baseline for assessing the impact of the COVID-19 pandemic on Hong Kong students’ physical fitness

Whole exome sequencing coupled with unbiased functional analysis reveals new Hirschsprung disease genes

Background: Hirschsprung disease (HSCR), which is congenital obstruction of the bowel, results from a failure of enteric nervous system (ENS) progenitors to migrate, proliferate, differentiate, or survive within the distal intestine. Previous studies that have searched for genes underlying HSCR have focused on ENS-related pathways and genes not fitting the current knowledge have thus often been ignored. We identify and validate novel HSCR genes using whole exome sequencing (WES), burden tests, in silico prediction, unbiased in vivo analyses of the mutated genes in zebrafish, and expression analyses in zebrafish, mouse, and human. Results: We performed de novo mutation (DNM) screening on 24 HSCR trios. We identify 28 DNMs in 21 different genes. Eight of the DNMs we identified occur in RET, the main HSCR gene, and the remaining 20 DNMs reside in genes not reported in the ENS. Knockdown of all 12 genes with missense or loss-of-function DNMs showed that the orthologs of four genes (DENND3, NCLN, NUP98, and TBATA) are indispensable for ENS development in zebrafish, and these results were confirmed by CRISPR knockout. These genes are also expressed in human and mouse gut and/or ENS progenitors. Importantly, the encoded proteins are linked to neuronal processes shared by the central nervous system and the ENS. Conclusions: Our data open new fields of investigation into HSCR pathology and provide novel insights into the development of the ENS. Moreover, the study demonstrates that functional analyses of genes carrying DNMs are warranted to delineate the full genetic architecture of rare complex diseases

Childhood Wheeze, Allergic Rhinitis, and Eczema in Hong Kong ISAAC Study from 1995 to 2015

Background: The prevalence of allergic diseases has been increasing in developing areas but has reached a plateau in many developed areas. Regular surveys are imperative to assess the disease burden for the prioritization of resource allocation. Objectives: We examined the change in the prevalence of wheezing, allergic rhinitis (AR), and eczema in school-aged children with possible associative factors and possible health effects of school air quality. Methods: This was the third repeated cross-sectional study conducted in 2015–2016 using the International Study of Asthma and Allergies in Childhood (ISAAC) protocol. Our first and second surveys were conducted in 1994–1995 and 2000–2001, respectively. Regarding the third survey, we recruited 3698 children aged 6–7 from 33 local schools in 18 districts. Air quality, temperature, and humidity were also measured. The changes in prevalence, multiple regression, and GLIMMIX procedure were analyzed. Results: From our first survey to our third survey, the increased prevalences for lifetime wheeze, current wheeze, lifetime rhinitis, current rhinitis, current rhinoconjunctivitis, lifetime chronic rash, and current chronic rash were 4.2%, 2.1%, 12.5%, 12.6%, 14.2%, 3.9%, and 4.1%, respectively. Increased prevalence of parental atopy had the strongest association with an increased prevalence of each of these seven health outcomes. There was no significant association between school air pollutant levels and the prevalence of health outcomes. Conclusions: There was an increase in the prevalence of wheezing, allergic rhinitis, and eczema across the surveys. The most important associated risk factor identified was the increased prevalence of a parental history of atopy

Identifying the High-Risk Population for COVID-19 Transmission in Hong Kong Leveraging Explainable Machine Learning

The worldwide spread of COVID-19 has caused significant damage to people’s health and economics. Many works have leveraged machine learning models to facilitate the control and treatment of COVID-19. However, most of them focus on clinical medicine and few on understanding the spatial dynamics of the high-risk population for transmission of COVID-19 in real-world settings. This study aims to investigate the association between population features and COVID-19 transmission risk in Hong Kong, which can help guide the allocation of medical resources and the implementation of preventative measures to control the spread of the pandemic. First, we built machine learning models to predict the number of COVID-19 cases based on the population features of different tertiary planning units (TPUs). Then, we analyzed the distribution of cases and the prediction results to find specific characteristics of TPUs leading to large-scale outbreaks of COVID-19. We further evaluated the importance and influence of various population features on the prediction results using SHAP values to identify indicators for high-risk populations for COVID-19 transmission. The evaluation of COVID-19 cases and the TPU dataset in Hong Kong shows the effectiveness of the proposed methods. The top three most important indicators are identified as people in accommodation and food services, low income, and high population density

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

Abstract 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