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Background: Children and adolescents with attention deficit hyperactivity disorder (ADHD) are at higher risk of all-cause poisoning by drugs and chemicals (intentional or accidental). Currently, there is limited data on whether medication treatment for ADHD can reduce the risk of all-cause poisoning., Methods: Patients aged 5-18 years with a methylphenidate (MPH) prescription and an incident poisoning diagnosis between January 2001 and June 2020 were identified from the Hong Kong Clinical Data Analysis and Reporting System. A self-controlled case series study design was used to compare the incidence rate ratios (IRRs) of all-cause poisoning during different risk windows (30 days before the first MPH prescription, exposure periods within 30 days of the first prescription, and periods of subsequent exposure) compared with the reference window (other non-exposure periods)., Results: 42,203 patients were prescribed ADHD medication in Hong Kong during the study period. Of these, 417 patients who had both an MPH prescription and poisoning incident recorded were included in the main analysis. Compared with other non-exposed periods, a higher risk of poisoning was found in the 30 days before the first prescription (IRR 2.64, 95% confidence interval [CI] 1.33-5.22) and exposure periods within 30 days of the first prescription (IRR 2.18, 95% CI 1.06-4.48), but not during prolonged exposure. However, compared with 30 days before the first prescription as well as exposure periods within 30 days of the first prescription, there was a lower risk during the subsequent exposure (IRRs 0.49 and 0.60, respectively). Similar results to the main analysis were also found in the subgroup analysis of intentional poisoning and females, but not in that of accidental poisoning and males., Conclusions: The risk of all-cause poisoning was higher shortly before and after the first MPH prescription and became lower during the subsequent prescription period. Our results do not support an association between the use of MPH and an increased risk of all-cause poisoning in children and adolescents and, in fact, suggest that longer-term use of MPH may be associated with a lower risk of all-cause poisoning, although this latter finding requires further study., (© 2021. The Author(s).)

Objectives: Data linkage of cohort-based data and electronic health records (EHRs) has been practised in many countries, but in Hong Kong there is still a lack of such research. To expand the use of multisource data, we aimed to identify a feasible way of linking two cohorts with EHRs in Hong Kong., Methods: Participants in the 'Children of 1997' birth cohort and the Chinese Early Development Instrument (CEDI) cohort were separated into several batches. The Hong Kong Identity Card Numbers (HKIDs) of each batch were then uploaded to the Hong Kong Clinical Data Analysis and Reporting System (CDARS) to retrieve EHRs. Within the same batch, each participant has a unique combination of date of birth and sex which can then be used for exact matching, as no HKID will be returned from CDARS. Raw data collected for the two cohorts were checked for the mismatched cases. After the matching, we conducted a simple descriptive analysis of attention deficit hyperactivity disorder (ADHD) information collected in the CEDI cohort via the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour Scale (SWAN) and EHRs., Results: In total, 3473 and 910 HKIDs in the birth cohort and CEDI cohort were separated into 44 and 5 batches, respectively, and then submitted to the CDARS, with 100% and 97% being valid HKIDs respectively. The match rates were confirmed to be 100% and 99.75% after checking the cohort data. From our illustration using the ADHD information in the CEDI cohort, 36 (4.47%) individuals had ADHD-Combined score over the clinical cut-off in the SWAN survey, and 68 (8.31%) individuals had ADHD records in EHRs., Conclusions: Using date of birth and sex as identifiable variables, we were able to link the cohort data and EHRs with high match rates. This method will assist in the generation of databases for future multidisciplinary research using both cohort data and EHRs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Nine years after the introduction of pneumococcal conjugate vaccine (PCV) in the United States, Hong Kong (HK) introduced the vaccine to its universal childhood immunisation programme in 2009. We aimed to assess the impact of childhood PCV immunisation on all-cause pneumonia (ACP) admissions among the overall population of HK., Methods: In this population-based interrupted time series analysis, we used territory-wide population-representative electronic health records in HK to evaluate the vaccine impact. We identified hospitalised patients with a diagnosis of pneumonia from any cause between 2004 and 2017. We applied segmented Poisson regression to assess the gradual change in the monthly incidence of ACP admissions between pre- and post-vaccination periods. Negative outcome control, subgroup and sensitivity analyses were used to test the robustness of the main analysis., Findings: Over the 14-year study period, a total of 587,607 ACP episodes were identified among 357,950 patients. The monthly age-standardised incidence of ACP fluctuated between 33.42 and 87.44 per 100,000-persons. There was a marginal decreasing trend in pneumonia admissions after PCV introduction among overall population (incidence rate ratio [IRR]: 0·9965, 95% confidence interval [CI]: 0·9932-0·9998), and older adults (≥65 years, IRR: 0·9928, 95% CI: 0·9904-0·9953) but not in younger age groups., Interpretation: There was a marginally declining trend of overall ACP admissions in HK up to eight years after childhood PCV introduction. The significance disappeared when fitting sensitivity analyses. The results indicate the complexities of using non-specific endpoints for measuring vaccine effect and the necessity of enhancing serotype surveillance systems for replacement monitoring., Funding: Health and Medical Research Fund, Food and Health Bureau of the Government of Hong Kong (Reference number: 18171272)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. X Li reports research and educational grants from Janssen, Pfizer, internal grants from University of Hong Kong, consulting fees from MSD, outside the submitted work. Dr. EW Chan reports other from Hospital Authority, grants from Research Grants Council (RGC, Hong Kong), grants from Research Fund Secretariat of the Food and Health Bureau, grants from National Natural Science Fund of China, grants from Wellcome Trust, grants from Bayer, grants from Bristol-Myers Squibb, grants from Pfizer, grants from Janssen, grants from Amgen, grants from Takeda, grants from Narcotics Division of the Security Bureau of HKSAR, outside the submitted work. Dr. IP has received research grants from Research Grants Council (RGC, Hong Kong) and Health and Medical Research Fund (HMRF), outside the submitted work. Professor BJ Cowling reports personal fees from Sanofi Pasteur, personal fees from Roche, outside the submitted work. Professor ICK Wong reports grants from Amgen, grants from Bristol-Myers Squibb, grants from Pfizer, grants from Janssen, grants from Bayer, grants from Bayer, grants from Novartis, grants from the Hong Kong Research Grants Council, grants from the Hong Kong Health and Medical Research Fund, grants from National Institute for Health Research in England, grants from European Commission, grants from National Health and Medical Research Council in Australia, outside the submitted work; and also received speaker fee from Janssen and Medice in previous 3 years. The other authors declared no conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to identify key factors affecting Healthcare workers (HCWs) perceived stress and risk of contracting COVID-19 among themselves and their family members during the pandemic. Methods: A cross-sectional online questionnaire study was conducted between 19 March and April 5, 2020 in Hong Kong. HCWs from public hospitals and private dentists, and their family members participated. Results: A total of 747 HCWs and 245 family members participated. Higher perceived stress in HCWs was associated with more negative changes in family relationship ( p = 0.025). The HCWs' perceived stress, however, was positively associated with family cohesion ( p = 0.033) and stress levels of family members ( p < 0.001). The level of HCWs' satisfaction toward the hospital policies in response to the COVID-19 outbreak was associated with lower levels of perceived stress and risk of themselves or their family members contracting COVID-19. HCWs' previous frontline experience of SARS was significantly associated with less perceived risk of themselves or their family members contracting COVID-19. Conclusion: Hospital policies addressing HCWs' needs, frontline experience of SARS, and family relationship influenced psychological wellbeing of HCWs during the COVID-19 outbreak., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chua, Tung, Kwan, Wong, Chui, Li, Wong, Tso, Fu, Chan, Wing, Chen, Chun Lee, Rao, Chan, Hon, Hung, Lau, Ho, Wong, Xiong, Chi, Tang, Tam, Wong and Ip.)

ABSTRACT As another wave of COVID-19 outbreak has approached in July 2020, a larger scale COVID-19 pediatric Asian cohort summarizing the clinical observations is warranted. Children confirmed with COVID-19 infection from the Republic of Korea, the Hong Kong Special Administrative Region (HKSAR) and Wuhan, China, during their first waves of local outbreaks were included. Their clinical characteristics and the temporal sequences of the first waves of local paediatric outbreaks were compared. Four hundred and twenty three children with COVID-19 were analyzed. Wuhan had the earliest peak, followed by Korea and HKSAR. Compared with Korea and Wuhan, patients in HKSAR were significantly older (mean age: 12.9 vs. 10.8 vs. 6.6 years, p  < 0.001, respectively) and had more imported cases (87.5% vs. 16.5% vs. 0%, p  < 0.001, respectively). The imported cases were also older (13.4 vs. 7.6 years, p  < 0.001). More cases in HKSAR were asymptomatic compared to Korea and Wuhan (45.5% vs. 22.0% vs. 20.9%, p  < 0.001, respectively), and significantly more patients from Wuhan developed fever (40.6% vs. 29.7% vs. 21.6%, p =0.003, respectively). There were significantly less imported cases than domestic cases developing fever after adjusting for age and region of origin ( p  = 0.046). 5.4% to 10.8% of patients reported anosmia and ageusia. None developed pediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PMIS-TS). In general, adolescents were more likely to be asymptomatic and less likely to develop fever, but required longer hospital stays. In conclusion, majority patients in this pediatric Asian cohort had a mild disease. None developed PIMS-TS. Their clinical characteristics were influenced by travel history and age.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.

Objectives: Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs., Methods: Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis., Results: One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs $3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001)., Conclusions: Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: The risk of liver injury in patients with atrial fibrillation (AF) using nonvitamin K antagonist oral anticoagulants (NOACs) has not been previously examined using liver function tests as the primary outcome in the real-world setting. This study assessed the association between NOACs (dabigatran, rivaroxaban, and apixaban) and warfarin and the risk of liver injury, as defined by laboratory tests., Methods: Patients newly diagnosed with AF and prescribed NOACs or warfarin between 2010 and 2016, identified using the Hong Kong Clinical Database and Reporting System, were matched on age, sex, health status scores, comorbidities, and medications by propensity score on a 1:1 ratio. Risk of liver injury, defined as laboratory test values >3 times the upper limit of normal of alanine aminotransferase or aspartate aminotransferase and >2 times the upper limit of normal of total bilirubin, was compared between NOAC and warfarin users using Cox proportional hazards regression., Results: After propensity score matching, 13,698 patients were included, of which 141 (2.1%) NOAC users and 232 (3.4%) warfarin users developed liver injury. The hazard ratio (HR) for NOAC vs warfarin users was 0.71 (95% confidence interval: 0.58-0.89). When comparing individual NOACs, only dabigatran (hazard ratio: 0.63; 95% confidence interval: 0.48-0.82) was associated with a lower risk of liver injury., Discussion: Among patients with AF, NOACs as a group, and dabigatran alone were associated with a significantly lower risk of laboratory-based liver injury when compared with warfarin. However, liver injury occurs more frequently in real-world practice than in NOAC randomized controlled trials.

Background: Studies have demonstrated that higher rates of antibiotic resistance are found in countries with higher antibiotic consumption. The global increase in antibiotic consumption is a major public health concern., Objectives: The objective of this study was to describe the antibiotic dispensing patterns in public hospitals in Hong Kong from 2000 to 2015., Methods: We acquired data on all hospital admissions with any antibiotics dispensed from 2000 to 2015 from the Hong Kong public hospitals. The annual proportion of hospital admissions with antibiotics dispensed was estimated and stratified by age group. An interrupted time series analysis was conducted to examine any potential change in tetracycline dispensing after the release of the new clinical practice guideline., Results: A total of 35,535,506 antibiotic prescriptions were dispensed among 2,161,360 unique hospitalized patients from 2000 to 2015. Antibiotics were dispensed in 29.2% of all hospital admissions in the public hospitals, the annual proportions of hospital admissions with antibiotics dispensed increased over the study period from 27.87% in 2000 to 31.39% in 2015, ranging from 27.17 to 31.39%. However, a significant increase was only observed in age groups of 5-19, 20-44, and 85 years or above when stratifying by age. In the interrupted time series analysis, a change in trend was detected for tetracycline dispensing that coincided with the time of publication of the new clinical practice guideline., Conclusions: We found that the overall volume of antibiotic use increased between 2000 and 2015. The rise in the dispensing of carbapenems in our study is concerning. The significant change in tetracycline use after being recommended as one of the preferred regimens demonstrated that the change in the clinical practice guideline had an immediate effect on the antibiotic prescribing practice in Hong Kong public hospitals.

Objectives: We aimed to describe patterns in the usage of antivirals to treat influenza virus infection in hospitals in Hong Kong from 2000 through 2015., Methods: We analyzed centralized electronic health records that included dispensation information and diagnosis codes. Information collected on admissions included patient age, sex, admission year and month, and medications dispensed, and were matched with the first 15 discharge diagnosis codes. We divided monthly admission episodes by relevant population denominators to obtain admission rates, and stratified analyses by drug type, age group, and diagnosis codes., Results: Amantadine was used for influenza treatment in the early 2000s but changed with recommendations to avoid its use in 2006, and is now mainly used to treat Parkinson's disease. Oseltamivir usage increased substantially in 2009 and is now commonly used, with almost 40,000 hospitalizations treated with oseltamivir in the years 2012 through 2015, 66% of which was in persons ≥65 years of age. During the entire study period, of the 98,253 admission episodes in which oseltamivir was dispensed, 40,698 (41%) included a diagnosis code for influenza, and 80,283 (82%) included any diagnosis code for respiratory illness., Conclusions: The amount of oseltamivir used from 2012-15 was comparable to a separate ecological estimate of around 13,000 influenza-associated hospitalizations per year on average. We did not have access to individual patient laboratory testing data.

Objective: To investigate the prevalence of ADHD medication prescribing of school-aged children in Hong Kong (HK) from 2001 to 2013 and to compare with other countries., Method: Using the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System, we investigated the epidemiology and prevalence of ADHD medication prescribing., Results: The prevalence of children on ADHD medication increased 14 times throughout the study period-0.072% in 2001 (95% confidence interval [CI] = [0.068%, 0.077%]) to 1.027% (95% CI = [1.008%, 1.047%]) in 2013. Prevalence in females increased at a faster rate than in males. The prescribing trend in kindergarten children (3- to 5-year-old) was relatively steady from 2001 to 2008-0.025% (95% CI = [0.019%, 0.033%]) in 2001-until a marked increase from 2009 to 2013-0.121% (95% CI = [0.105%, 0.139%]) in 2013., Conclusion: The prevalence of ADHD medication prescribing in Hong Kong is increasing but remains lower than most Western countries. However, the prevalence of ADHD medication prescribing for kindergarten children should be monitored to ensure appropriate use.

Purpose: Antipsychotic-prescribing patterns remain unclear in Asia. The aims of our study were to investigate prescribing trends of antipsychotic medication in the general population, children, and older patients by drug generation (first or second), the prescribing trend in pregnant women, the probable indication for antipsychotic prescription, and the prescribing trend by dosage form., Methods: This descriptive study identified and included all patients prescribed with antipsychotic in Hong Kong from 2004 to 2014 using the Clinical Data Analysis and Report System. This study calculated and reported the prevalence of antipsychotic prescribing in patient groups of interest, the percentage with diagnoses of mental disorders were derived, and the prevalence of antipsychotic by dosage forms., Results: The study included 10 109 206 prescriptions of any antipsychotics to 256 903 patients. Over the study period, the prevalence of antipsychotic prescribing increased from 1.06% to 1.54% in the general population, from 0.10% to 0.23% in children (3-17 years old), and from 2.61% to 3.26% in older patients (≥65 years old). The prevalence of second-generation antipsychotics increased, but the prevalence of first-generation antipsychotics did not. Prevalence of antipsychotic prescribing in prepregnancy, pregnancy, and postpartum timeframes varied from 0.18% to 0.38%. The percentage of incident prescriptions with a diagnosis of psychosis decreased from 54.1% to 47.5%., Conclusions: Antipsychotics have been increasingly prescribed in the general population, children, and older patients. There is an increase in second-generation antipsychotic prescribing. Over half of incident users had a recent diagnosis of a nonpsychotic mental disorder in 2014, suggesting that off-label prescribing of antipsychotics might be common., (Copyright © 2017 John Wiley & Sons, Ltd.)