Publications by authors named "Ian C K Wong"

261 Publications

Prescription Patterns of Antidementia and Psychotropic Drugs in People Living With Dementia: Findings From the Clinical Pathway Study of Alzheimer's Disease in China.

J Am Med Dir Assoc 2021 Aug 18. Epub 2021 Aug 18.

Dementia Care & Research Center, Peking University Institute of Mental Health (Sixth Hospital), Beijing, China; Beijing Municipal Key Laboratory for Translational Research on Diagnosis and Treatment of Dementia, Beijing, China; Key Laboratory for Mental Health, Ministry of Health (Peking University), Beijing, China. Electronic address:

Objectives: Evidence about prescribing patterns of dementia medication in China is lacking. This study aimed to examine prescribing rates of antidementia and psychotropic drugs and factors associated with drug prescription for dementia in China.

Design: A multicenter observational study.

Setting And Participants: This study employed cross-sectional data from the Clinical Pathway for Alzheimer's Disease in China study that was conducted in 28 memory clinics at tertiary hospitals across 14 provinces between 2012 and 2013. Patients aged ≥45 years with a diagnosis of dementia were included.

Methods: Antidementia and psychotropic drugs were classified according to the Anatomical Therapeutic Chemical codes. Odds ratios (ORs) of putative factors associated with prescription patterns were estimated using logistic regressions.

Results: A total of 751 respondents were included in this study, 77.8% of whom were prescribed antidementia drugs, and 33.0% were prescribed at least 1 psychotropic drug. The concomitant prescription rate of antidementia and psychotropic drugs was 24.1%. Frontotemporal dementia [OR 9.92 (99.17% CI 3.08-42.70)], severe dementia [4.25 (1.88-9.79)], and apathy [1.94 (1.18-3.20)] were significantly associated with an elevated likelihood of memantine prescription. Psychotic symptoms [1.84 (1.02-3.35)], agitation [1.91 (1.08-3.40)], and depressive symptoms [2.10 (1.12-3.94)] were significantly associated with the coprescription of antidementia and psychotropic agents.

Conclusions And Implications: The prescribing rate of antidementia drugs in the study sample was higher, whereas the rate of coprescription of psychotropic and antidementia drugs was lower than reported in Western studies. Dementia prescription practice was generally consistent with clinical guidelines in memory clinics in China, whereas the prescription of antidementia and psychotropic medication mainly depended on patients' clinical symptoms.
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http://dx.doi.org/10.1016/j.jamda.2021.07.017DOI Listing
August 2021

Inconsistent Safety Outcome Reporting in Randomized Clinical Trials of COVID-19 Vaccines Complicates Informed Medical Decisions.

Drug Saf 2021 Aug 17. Epub 2021 Aug 17.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, General Office, L02-56 2/F Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China.

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http://dx.doi.org/10.1007/s40264-021-01108-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370447PMC
August 2021

Association Between Prenatal Exposure to Antipsychotics and Attention-Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Preterm Birth, and Small for Gestational Age.

JAMA Intern Med 2021 Aug 16. Epub 2021 Aug 16.

Research Department of Practice and Policy, UCL School of Pharmacy, London, England.

Importance: The risk of birth and neurodevelopmental complications with prenatal exposure to antipsychotics is unclear.

Objective: To evaluate the association between prenatal antipsychotics exposure and the risk of birth and neurodevelopmental problems.

Design, Setting, And Participants: This population-based cohort study included children born between January 2001 and January 2015 with follow-up to December 2019 who were identified by the Hong Kong Clinical Data Analysis and Reporting System. Pregnancies with maternal antidepressant/lithium exposure were removed. Primary analyses compared gestationally exposed and gestationally nonexposed individuals with propensity score fine stratification. Additional analyses included gestationally exposed individuals vs those with past exposure and a sibling-matched analysis to evaluate the effect of confounding by indication.

Exposures: Prenatal antipsychotic exposure.

Main Outcomes And Measures: Preterm birth (<37 gestational weeks), small for gestational age (birth weight <2 standard deviations below the mean for gestational age), and first diagnosis of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children.

Results: The cohorts included 333 749 mother-child pairs for ADHD (mean [SD] maternal age at delivery, 31.46 [5.03] years) and 411 251 pairs for ASD, preterm birth, and small for gestational age analyses (mean [SD] maternal age at delivery, 31.56 [5.01] years). There were 13 196 children (3.95%) with a diagnosis of ADHD, 8715 (2.12%) with ASD, 33 891 (8.24%) preterm, and 7009 (1.70%) who were small for gestational age. The weighted hazard ratio (wHR) was 1.16 (95% CI, 0.83-1.61) for ADHD and 1.06 (95% CI, 0.70-1.60) for ASD, while the weighted odds ratio (wOR) was 1.40 (95% CI, 1.13-1.75) for preterm birth and 1.36 (95% CI, 0.86-2.14) for small for gestational age when comparing gestationally exposed with gestationally nonexposed individuals. Additional analyses showed no association when comparing gestationally exposed individuals with those with past exposure (ADHD: wHR, 0.99; 95% CI, 0.60-1.61; ASD: wHR, 1.10; 95% CI, 0.58-2.08; preterm birth: wOR, 0.93; 95% CI, 0.70-1.24; small for gestational age: wOR, 1.21; 95% CI, 0.66-2.20) and in a sibling-matched analysis (ADHD: wHR, 0.41; 95% CI, 0.04-4.93; ASD: wHR, 0.90; 95% CI, 0.40-2.01; preterm birth: wOR, 1.25; 95% CI, 0.85-1.82; small for gestational age: wOR, 0.86, 95% CI, 0.32-2.31).

Conclusions And Relevance: In this cohort study, the findings did not suggest that prenatal antipsychotics exposure increased the risk of ADHD, ASD, or small for gestational age. In the primary analysis, there was a small increased risk of preterm birth, but additional analyses comparing gestationally exposed individuals with those with past exposure and comparing gestationally exposed with gestationally nonexposed siblings did not support an increased risk. Given the benefits of treating psychosis during pregnancy, our findings do not support a recommendation for women to discontinue receipt of their regular antipsychotic treatment during pregnancy.
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http://dx.doi.org/10.1001/jamainternmed.2021.4571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369381PMC
August 2021

Global trends in symptomatic medication use against dementia in 66 countries/regions from 2008 to 2018.

Eur J Neurol 2021 Aug 7. Epub 2021 Aug 7.

Research Department of Practice and Policy, School of Pharmacy, University College London, London, UK.

Background And Purpose: The aim was to determine trends and patterns of symptomatic medication used against dementia in 66 countries and regions.

Methods: This was a cross-sectional study that used the wholesale data from the IQVIA Multinational Integrated Data Analysis System database. Sale data for symptomatic medication against dementia from 66 countries and regions from 2008 to 2018 were analysed and stratified by income level (low/middle-income countries [LMICs], n = 27; high-income countries [HICs], n = 37; regions, n = 2). The medication use volume was estimated by defined daily dose (DDD) per 1000 inhabitants per day (World Health Organization DDD harmonized the size, strength and form of each pack and reflects average dosing). Changes in medication use over time were quantified as percentage changes in compound annual growth rates (CAGRs).

Results: Total symptomatic medication against dementia sales increased from 0.85 to 1.33 DDD per 1000 inhabitants per day between 2008 and 2018 (LMICs 0.094-0.396; HICs 3.88-5.04), which is an increase of CAGR of 4.53% per year. The increase was mainly driven by the LMICs (CAGR = 15.42%) in comparison to the HICs (CAGR = 2.65%). The overall medication use from 2008 to 2018 increased for all four agents: memantine (CAGR = 8.51%), rivastigmine (CAGR = 6.91%), donepezil (CAGR = 2.72%) and galantamine (CAGR = 0.695%). In 2018, the most commonly used medication globally was donepezil, contributing to 49.8% of total use volume, followed by memantine (32.7%), rivastigmine (11.24%) and galantamine (6.36%).

Conclusion: There was an increasing trend in the use of symptomatic medications against dementia globally, but the use remained low in LMICs. Interventions may be needed to support the medication use in some countries.
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http://dx.doi.org/10.1111/ene.15053DOI Listing
August 2021

Global epidemiology of hip fractures: a study protocol using a common analytical platform among multiple countries.

BMJ Open 2021 07 28;11(7):e047258. Epub 2021 Jul 28.

School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.

Introduction: Hip fractures are associated with a high burden of morbidity and mortality. Globally, there is wide variation in the incidence of hip fracture in people aged 50 years and older. Longitudinal and cross-geographical comparisons of health data can provide insights on aetiology, risk factors, and healthcare practices. However, systematic reviews of studies that use different methods and study periods do not permit direct comparison across geographical regions. Thus, the objective of this study is to investigate global secular trends in hip fracture incidence, mortality and use of postfracture pharmacological treatment across Asia, Oceania, North and South America, and Western and Northern Europe using a unified methodology applied to health records.

Methods And Analysis: This retrospective cohort study will use a common protocol and an analytical common data model approach to examine incidence of hip fracture across population-based databases in different geographical regions and healthcare settings. The study period will be from 2005 to 2018 subject to data availability in study sites. Patients aged 50 years and older and hospitalised due to hip fracture during the study period will be included. The primary outcome will be expressed as the annual incidence of hip fracture. Secondary outcomes will be the pharmacological treatment rate and mortality within 12 months following initial hip fracture by year. For the primary outcome, crude and standardised incidence of hip fracture will be reported. Linear regression will be used to test for time trends in the annual incidence. For secondary outcomes, the crude mortality and standardised mortality incidence will be reported.

Ethics And Dissemination: Each participating site will follow the relevant local ethics and regulatory frameworks for study approval. The results of the study will be submitted for peer-reviewed scientific publications and presented at scientific conferences.
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http://dx.doi.org/10.1136/bmjopen-2020-047258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319985PMC
July 2021

Use of Primary Care Data in Research and Pharmacovigilance: Eight Scenarios Where Prescription Data are Absent.

Drug Saf 2021 Jul 22. Epub 2021 Jul 22.

Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, London, UK.

The use of primary care databases has been integral in pharmacoepidemiological studies and pharmacovigilance. Primary care databases derive from electronic health records and offer a comprehensive description of aggregate patient data, from demography to medication history, and good sample sizes. Studies using these databases improve our understanding of prescribing characteristics and associated risk factors to facilitate better patient care, but there are limitations. We describe eight key scenarios where study data outcomes can be affected by absent prescriptions in UK primary care databases: (1) out-of-hours, urgent care and acute care prescriptions; (2) specialist-only prescriptions; (3) alternative community prescribing, such as pharmacy, family planning clinic or sexual health clinic medication prescriptions; (4) newly licensed medication prescriptions; (5) medications that do not require prescriptions; (6) hospital inpatient and outpatient prescriptions; (7) handwritten prescriptions; and (8) private pharmacy and private doctor prescriptions. The significance of each scenario is dependent on the type of medication under investigation, nature of the study and expected outcome measures. We recommend that all researchers using primary care databases be aware of the potential for missing prescribing data and be sensitive to how this can vary substantially between items, drug classes, patient groups and over time. Close liaison with practising primary care clinicians in the UK is often essential to ensure awareness of nuances in clinical practice.
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http://dx.doi.org/10.1007/s40264-021-01093-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297607PMC
July 2021

Treatment with Methylphenidate for Attention Deficit Hyperactivity Disorder (ADHD) and the Risk of All-Cause Poisoning in Children and Adolescents: A Self-Controlled Case Series Study.

CNS Drugs 2021 Jul 20;35(7):769-779. Epub 2021 Jul 20.

Department of Pharmacology and Pharmacy, Centre for Safe Medication Practice and Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 2/F Laboratory Block, 21 Sassoon Road, Hong Kong, China.

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.
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http://dx.doi.org/10.1007/s40263-021-00824-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310501PMC
July 2021

Association between methylphenidate and risk of myocardial infarction: A multinational self-controlled case series study.

Pharmacoepidemiol Drug Saf 2021 Oct 13;30(10):1458-1467. Epub 2021 Jul 13.

School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea.

Purpose: To investigate the association between use of methylphenidate and risk of myocardial infarction among Asians.

Methods: We conducted a multinational self-controlled case series study using nationwide healthcare databases of South Korea (2002-2018), Taiwan (2004-2015), and Hong Kong (2001-2016). Of patients with myocardial infarction who were also prescribed methylphenidate within the observation period, methylphenidate use was classified into four mutually exclusive periods by each person-day: exposed (exposed to methylphenidate), pre-exposure (prior to the first methylphenidate prescription), washout (after the end of methylphenidate treatment), and baseline (unexposed to methylphenidate). Risk of myocardial infarction among the three periods of methylphenidate use was compared to the baseline period using conditional Poisson regression analysis to estimate incidence rate ratios (IRRs) with 95% confidence intervals (CIs).

Results: We identified 2104, 484, and 30 patients from South Korea, Taiwan, and Hong Kong, respectively. Risk of myocardial infarction was the highest during the pre-exposure period in all three populations: South Korea, pre-exposure (IRR 3.17, 95% CI 3.04-3.32), exposed (1.05, 1.00-1.11), washout (1.92, 1.80-2.04); Taiwan, pre-exposure (1.97, 1.78-2.17), exposed (0.72, 0.65-0.80), washout (0.56, 0.46-0.68); Hong Kong, pre-exposure (18.09, 8.19-39.96), exposed (9.32, 3.44-25.28), washout (7.69, 1.72-34.41). Following stratification for age and sex, the trends remained analogous to the main findings across all three populations.

Conclusions: Although a positive association between initiating methylphenidate and the onset of myocardial infarction was observed, the risk was the highest in the period before its initiation. Thus, this multinational study suggests there was no causal relationship between methylphenidate and myocardial infarction among Asians.
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http://dx.doi.org/10.1002/pds.5322DOI Listing
October 2021

Bipolar disorder prevalence and psychotropic medication utilisation in Hong Kong and the United Kingdom.

Pharmacoepidemiol Drug Saf 2021 Jun 28. Epub 2021 Jun 28.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong.

Purpose: Bipolar disorder (BPD) is often an under-addressed mental disorder. Limited studies have investigated its epidemiology and drug utilisation in Hong Kong (HK) and the United Kingdom (UK) and thus local prescribing practices remain unclear. This study aimed to determine the prevalence of BPD and the prescribing of psychotropic medications as maintenance treatment from 2001-2018 in HK and the UK.

Method: A retrospective study using the data from Clinical Data Analysis and Reporting System in HK and IQVIA Medical Research Data in the UK.

Results: The prevalence of BPD diagnosis in HK and the UK more than doubled during the study period. Some distinct changes in prescribing patterns over time were observed. Lithium use declined by 2.46% and 14.58% in HK and the UK, respectively. By 2018, patients were 4.6 times more likely to receive antidepressant monotherapy in the UK versus HK (15.62% vs. 3.42%). In HK, 38.41% of women of childbearing age were prescribed valproate in 2018 compared with 8.46% in the UK.

Conclusion: The prevalence of BPD diagnosis has been increasing in HK and the UK. The disparity in prescribing patterns of BPD maintenance treatment in two regions reflected three major issues in clinical practice: (1) under-prescribing of lithium in both regions, (2) antidepressant monotherapy in the UK and (3) overprescribing of valproate to women of childbearing age in HK. A review of current clinical treatment guidelines and regulations of prescribing practice by local clinicians should be immediately implemented to ensure the safe use of medications in patients with BPD.
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http://dx.doi.org/10.1002/pds.5318DOI Listing
June 2021

Drug Repurposing for the Treatment of COVID-19: A Knowledge Graph Approach.

Adv Ther (Weinh) 2021 May 20:2100055. Epub 2021 May 20.

Centre for Safe Medication Practice and Research Department of Pharmacology and Pharmacy LKS Faculty of Medicine University of Hong Kong Hong Kong Special Administrative Region, 1/F, Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road Pokfulam Hong Kong SAR China.

Identifying effective drug treatments for COVID-19 is essential to reduce morbidity and mortality. Although a number of existing drugs have been proposed as potential COVID-19 treatments, effective data platforms and algorithms to prioritize drug candidates for evaluation and application of knowledge graph for drug repurposing have not been adequately explored. A COVID-19 knowledge graph by integrating 14 public bioinformatic databases containing information on drugs, genes, proteins, viruses, diseases, symptoms and their linkages is developed. An algorithm is developed to extract hidden linkages connecting drugs and COVID-19 from the knowledge graph, to generate and rank proposed drug candidates for repurposing as treatments for COVID-19 by integrating three scores for each drug: motif scores, knowledge graph PageRank scores, and knowledge graph embedding scores. The knowledge graph contains over 48 000 nodes and 13 37 000 edges, including 13 563 molecules in the DrugBank database. From the 5624 molecules identified by the motif-discovery algorithms, ranking results show that 112 drug molecules had the top 2% scores, of which 50 existing drugs with other indications approved by health administrations reported. The proposed drug candidates serve to generate hypotheses for future evaluation in clinical trials and observational studies.
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http://dx.doi.org/10.1002/adtp.202100055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212091PMC
May 2021

Linking cohort-based data with electronic health records: a proof-of-concept methodological study in Hong Kong.

BMJ Open 2021 06 22;11(6):e045868. Epub 2021 Jun 22.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong

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.
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http://dx.doi.org/10.1136/bmjopen-2020-045868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220454PMC
June 2021

Trends in lipid-modifying agent use in 83 countries.

Atherosclerosis 2021 07 27;328:44-51. Epub 2021 May 27.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, University of Hong Kong, Hong Kong; Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong; The University of Hong Kong Shenzhen Institute of Research and Innovation, China; Department of Pharmacy, HKU-Shenzhen Hospital, China. Electronic address:

Background And Aims: Lipid-modifying agents (LMAs) are increasingly used to reduce lipid levels and prevent cardiovascular events but the magnitude of their consumption in different world regions is unknown. We aimed to describe recent global trends in LMA consumption and to explore the relationship between country-level LMA consumption and cholesterol concentrations.

Methods: This cross-sectional and ecological study used monthly pharmaceutical sales data from January 2008 to December 2018 for 83 countries from the IQVIA Multinational Integrated Data Analysis System and total and non-high-density lipoprotein (non-HDL) cholesterol concentrations from the NCD Risk Factor Collaboration. Compound annual growth rate (CAGR) was used to assess changes in LMA consumption over time.

Results: From 2008 to 2018, use of LMAs increased from 7468 to 11,197 standard units per 1000 inhabitants per year (CAGR 4.13%). An estimated 173 million people used LMAs in 2018. Statins were the most used class of LMA and their market share increased in 75% of countries between 2008 and 2018. From 2013 to 2018, consumption of low-density lipoprotein lowering therapies increased (statins 3.99%; ezetimibe 4.01%; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors 104.47%). Limited evidence supports a clear relationship between country-level changes in LMA consumption and mean total and non-HDL cholesterol concentrations in 2008 versus 2018.

Conclusions: Since 2008, global access to LMAs, especially statins, has improved. In line with international lipid guideline recommendations, recent trends indicate growth in the use of statins, ezetimibe, and PCSK9 inhibitors. Country-level patterns of LMA use and total and non-HDL cholesterol varied considerably.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.05.016DOI Listing
July 2021

Impact of Snoring on Telomere Shortening in Adolescents with Atopic Diseases.

Genes (Basel) 2021 05 18;12(5). Epub 2021 May 18.

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China.

Atopic diseases can impose a significant burden on children and adolescents. Telomere length is a cellular marker of aging reflecting the impact of cumulative stress exposure on individual health. Since elevated oxidative stress and inflammation burden induced by chronic atopy and snoring may impact telomere length, this study aimed to investigate whether snoring would moderate the relationship between atopic diseases and telomere length in early adolescence. We surveyed 354 adolescents and their parents. Parents reported the adolescents' history of atopic diseases, recent snoring history as well as other family sociodemographic characteristics. Buccal swab samples were also collected from the adolescents for telomere length determination. Independent and combined effects of atopic diseases and snoring on telomere length were examined. Among the surveyed adolescents, 174 were reported by parents to have atopic diseases (20 had asthma, 145 had allergic rhinitis, 53 had eczema, and 25 had food allergy). Shorter TL was found in participants with a history of snoring and atopic diseases (β = -0.34, = 0.002) particularly for asthma (β = -0.21, = 0.007) and allergic rhinitis (β = -0.22, = 0.023). Our findings suggest that snoring in atopic patients has important implications for accelerated telomere shortening. Proper management of atopic symptoms at an early age is important for the alleviation of long-term health consequences at the cellular level.
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http://dx.doi.org/10.3390/genes12050766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157836PMC
May 2021

A Longitudinal Study of the Relation between Childhood Activities and Psychosocial Adjustment in Early Adolescence.

Int J Environ Res Public Health 2021 05 16;18(10). Epub 2021 May 16.

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China.

Background: Although an increasing body of research shows that excessive screen time could impair brain development, whereas non-screen recreational activities can promote the development of adaptive emotion regulation and social skills, there is a lack of comparative research on this topic. Hence, this study examined whether and to what extent the frequency of early-life activities predicted later externalizing and internalizing problems.

Methods: In 2012/13, we recruited Kindergarten 3 (K3) students from randomly selected kindergartens in two districts of Hong Kong and collected parent-report data on children's screen activities and parent-child activities. In 2018/19, we re-surveyed the parents of 323 students (aged 11 to 13 years) with question items regarding their children's externalizing and internalizing symptoms in early adolescence. Linear regression analyses were conducted to examine the associations between childhood activities and psychosocial problems in early adolescence.

Results: Early-life parent-child activities (β = -0.14, = 0.012) and child-alone screen use duration (β = 0.15, = 0.007) independently predicted externalizing problems in early adolescence. Their associations with video game exposure (β = 0.19, = 0.004) and non-screen recreational parent-child activities (β = -0.14, = 0.004) were particularly strong.

Conclusions: Parent-child play time is important for healthy psychosocial development. More efforts should be directed to urge parents and caregivers to replace child-alone screen time with parent-child play time.
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http://dx.doi.org/10.3390/ijerph18105299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157182PMC
May 2021

The association between attention-deficit/hyperactivity disorder and retinal nerve fiber/ganglion cell layer thickness measured by optical coherence tomography: a systematic review and meta-analysis.

Int Ophthalmol 2021 Sep 20;41(9):3211-3221. Epub 2021 May 20.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong.

Purpose: Retinal nerve fiber/ganglion cell layer (RNFL/GCL) thickness measured using optical coherence tomography has been proposed as an ocular biomarker for children with attention-deficit/hyperactivity disorder (ADHD), but findings varied in different studies. This study aims to determine the association between RNFL/GCL thickness and ADHD in children by systematic review and meta-analysis.

Methods: We performed a literature search in Embase, PubMed, Medline, Web of Science, and PsycINFO for relevant articles published up to February 29, 2020. All studies with original data comparing RNFL/GCL thickness in ADHD and healthy children were included. The Newcastle Ottawa Scale was used to assess bias risk and quality of evidence. Pooled estimates of the differences in thickness of RNFL or GCL between ADHD and healthy subjects were generated using meta-analysis with a random-effect model due to significant inter-study heterogeneity. Sensitivity analysis was also performed.

Results: We identified four eligible studies involving a total of 164 ADHD and 150 control subjects. Meta-analysis revealed that ADHD in children was associated with a reduction in global RNFL thickness (SMD, - 0.23; 95% CI - 0.46, - 0.01; p = 0.04). The global GCL thickness was examined in two studies with 89 ADHD and 75 control subjects, but the pooled difference in global GCL thickness between ADHD children and controls was not statistically significant (SMD, - 0.34; 95% CI - 1.25, 0.58; p = 0.47).

Conclusion: Existing evidence suggests a possible association between ADHD and RNFL thinning in children. In view of the limited number of reports, further studies in large cohorts should be warranted.
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http://dx.doi.org/10.1007/s10792-021-01852-8DOI Listing
September 2021

Clinical Characteristics and Transmission of COVID-19 in Children and Youths During 3 Waves of Outbreaks in Hong Kong.

JAMA Netw Open 2021 05 3;4(5):e218824. Epub 2021 May 3.

Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.

Importance: Schools were closed intermittently across Hong Kong to control the COVID-19 outbreak, which led to significant physical and psychosocial problems among children and youths.

Objective: To compare the clinical characteristics and sources of infection among children and youths with COVID-19 during the 3 waves of outbreaks in Hong Kong in 2020.

Design, Setting, And Participants: This cross-sectional study involved children and youths aged 18 years or younger with COVID-19 in the 3 waves of outbreaks from January 23 through December 2, 2020. Data were analyzed from December 2020 through January 2021.

Main Outcomes And Measures: Demographic characteristics, travel and contact histories, lengths of hospital stay, and symptoms were captured through the central electronic database. Individuals who were infected without recent international travel were defined as having domestic infections.

Results: Among 397 children and youths confirmed with COVID-19 infections, the mean (SD) age was 9.95 (5.34) years, 220 individuals (55.4%) were male, and 154 individuals (38.8%) were asymptomatic. There were significantly more individuals who were infected without symptoms in the second wave (59 of 118 individuals [50.0%]) and third wave (94 of 265 individuals [35.5%]) than in the first wave (1 of 14 individuals [7.1%]) (P = .001). Significantly fewer individuals who were infected in the second and third waves, compared with the first wave, had fever (first wave: 10 individuals [71.4%]; second wave: 22 individuals [18.5%]; third wave: 98 individuals [37.0%]; P < .001) or cough (first wave: 6 individuals [42.9%]; second wave: 15 individuals [12.7%]; third wave: 52 individuals [19.6%]; P = .02). Among all individuals, 394 individuals (99.2%) had mild illness. One patient developed chilblains (ie, COVID toes), 1 patient developed multisystem inflammatory syndrome in children, and 1 patient developed post-COVID-19 autoimmune hemolytic anemia. In all 3 waves, 204 patients with COVID-19 (51.4%) had domestic infections. Among these individuals, 186 (91.2%) reported having a contact history with another individual with COVID-19, of which most (183 individuals [90.0%]) were family members. In the third wave, 18 individuals with domestic infections had unknown contact histories. Three schoolmates were confirmed with COVID-19 on the same day and were reported to be close contacts.

Conclusions And Relevance: This cross-sectional study found that nearly all children and youths with COVID-19 in Hong Kong had mild illness. These findings suggest that household transmission was the main source of infection for children and youths with domestic infections and that the risk of being infected at school was small.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.8824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094012PMC
May 2021

Impact of COVID-19 Pandemic on Serum Vitamin D Level among Infants and Toddlers: An Interrupted Time Series Analysis and before-and-after Comparison.

Nutrients 2021 Apr 13;13(4). Epub 2021 Apr 13.

Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong, China.

: During the coronavirus disease 2019 (COVID-19) pandemic, the implementation of social distancing and home confinement measures may elevate the risk of vitamin D deficiency particularly for infants. This study aimed to quantify changes in vitamin D level among infants and toddlers in Hong Kong after the COVID-19 outbreak. We recruited 303 infants and toddlers aged 2-24 months by stratified random sampling from 1 June 2019 to November 30, 2020. Regression models were used to estimate the effect of time on infants' serum 25-hydroxyvitamin D (25(OH)D) level overall and by age groups before and after the outbreak. Interrupted time series (ITS) analysis was performed to examine the sustained effect of COVID-19 on their serum 25(OH)D level. The ITS results showed no immediate reduction in serum 25(OH)D level among infants, but a decreasing trend was observed in the subsequent months post-outbreak at a monthly decline rate of -6.32 nmol/L. When analyzed by age group, the magnitude of post-outbreak reduction in 25(OH)D was stronger among younger infants (aged 2-6 months). Guidelines and recommendations should be given to pregnant women and mothers to ensure sufficient vitamin D level in their infants during the COVID-19 period.
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http://dx.doi.org/10.3390/nu13041270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069706PMC
April 2021

Prediction of individuals at high risk of chronic kidney disease during treatment with lithium for bipolar disorder.

BMC Med 2021 04 28;19(1):99. Epub 2021 Apr 28.

Division of Psychiatry, UCL, London, UK.

Background: Lithium is the most effective treatment in bipolar disorder. Its use is limited by concerns about risk of chronic kidney disease (CKD). We aimed to develop a model to predict risk of CKD following lithium treatment initiation, by identifying individuals with a high-risk trajectory of kidney function.

Methods: We used United Kingdom Clinical Practice Research Datalink (CPRD) electronic health records (EHRs) from 2000 to 2018. CPRD Aurum for prediction model development and CPRD Gold for external validation. We used elastic net regularised regression to generate a prediction model from potential features. We performed discrimination and calibration assessments in an external validation data set. We included all patients aged ≥ 16 with bipolar disorder prescribed lithium. To be included patients had to have ≥ 1 year of follow-up before lithium initiation, ≥ 3 estimated glomerular filtration rate (eGFR) measures after lithium initiation (to be able to determine a trajectory) and a normal (≥ 60 mL/min/1.73 m) eGFR at lithium initiation (baseline). In the Aurum development cohort, 1609 fulfilled these criteria. The Gold external validation cohort included 934 patients. We included 44 potential baseline features in the prediction model, including sociodemographic, mental and physical health and drug treatment characteristics. We compared a full model with the 3-variable 5-year kidney failure risk equation (KFRE) and a 3-variable elastic net model. We used group-based trajectory modelling to identify latent trajectory groups for eGFR. We were interested in the group with deteriorating kidney function (the high-risk group).

Results: The high risk of deteriorating eGFR group included 191 (11.87%) of the Aurum cohort and 137 (14.67%) of the Gold cohort. Of these, 168 (87.96%) and 117 (85.40%) respectively developed CKD 3a or more severe during follow-up. The model, developed in Aurum, had a ROC area of 0.879 (95%CI 0.853-0.904) in the Gold external validation data set. At the empirical optimal cut-point defined in the development dataset, the model had a sensitivity of 0.91 (95%CI 0.84-0.97) and a specificity of 0.74 (95% CI 0.67-0.82). However, a 3-variable elastic net model (including only age, sex and baseline eGFR) performed similarly well (ROC area 0.888; 95%CI 0.864-0.912), as did the KFRE (ROC area 0.870; 95%CI 0.841-0.898).

Conclusions: Individuals at high risk of a poor eGFR trajectory can be identified before initiation of lithium treatment by a simple equation including age, sex and baseline eGFR. Risk was increased in individuals who were younger at commencement of lithium, female and had a lower baseline eGFR. We did not identify strong predicters of eGFR decline specific to lithium-treated patients. Notably, lithium duration and toxicity were not associated with high-risk trajectory.
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http://dx.doi.org/10.1186/s12916-021-01964-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080385PMC
April 2021

The impact of childhood pneumococcal conjugate vaccine immunisation on all-cause pneumonia admissions in Hong Kong: A 14-year population-based interrupted time series analysis.

Vaccine 2021 05 12;39(19):2628-2635. Epub 2021 Apr 12.

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Centre for Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.

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).
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http://dx.doi.org/10.1016/j.vaccine.2021.03.090DOI Listing
May 2021

Prenatal exposure to antipsychotic agents and the risk of congenital malformations in children: A systematic review and meta-analysis.

Br J Clin Pharmacol 2021 Mar 27. Epub 2021 Mar 27.

Research Department of Practice and Policy, UCL School of Pharmacy, London, UK.

Objective: To evaluate the association between antipsychotic use in pregnancy and the risk of congenital malformations in children.

Data Sources: Searches of PubMed, EMBASE, PsycINFO and Cochrane Library were conducted from inception to 06 January 2020 using keywords: antipsychotics, pregnancy, pregnancy complication and congenital abnormalities.

Study Selection: Of 38 reports initially identified as being of potential interest, 13 studies met our inclusion criteria: English observational studies that examined the association between gestational antipsychotic use and congenital malformations in children.

Data Extraction: Data were extracted independently by 2 investigators including the publication year, study site, study period, data source, study design, sample size, medication exposure, exposure period and pregnancy definition, exposure as well as outcome ascertainment, selection of study and comparison group, confounding adjustment, statistical analysis, and method of linkage between mother and children. Risk estimates were pooled using a random-effect model and the I statistic was used to evaluate the degree of heterogeneity.

Results: Thirteen studies met our systematic review inclusion criteria. Six studies with a total of 2 515 272 pregnancy episodes were included in our meta-analysis, which provided a pooled adjusted risk ratio of 1.23, 95% confidence interval: 0.96-1.58. The I result showed moderate heterogeneity between studies (I = 35.2%, P = .173).

Conclusion: We did not find strong evidence of an association between prenatal exposure to antipsychotic medications and the risk of congenital malformations in children. We recommend further studies investigate this association, focusing on specific medication classes and dose responses, which would help clinicians decide whether to prescribe certain antipsychotics during pregnancy.
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http://dx.doi.org/10.1111/bcp.14839DOI Listing
March 2021

Treatment with direct oral anticoagulants or warfarin and the risk for incident diabetes among patients with atrial fibrillation: a population-based cohort study.

Cardiovasc Diabetol 2021 03 25;20(1):71. Epub 2021 Mar 25.

Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.

Background: Diabetes mellitus is a common comorbidity of atrial fibrillation (AF), which can complicate the management of AF. The pharmacology of oral anticoagulants (OACs) have been implicated in pathogenesis of diabetes, but the relationship between different OACs and risk of diabetes remains unexamined. This study aimed to evaluate the risk of diabetes with use of different OACs in AF patients.

Methods: Population-based retrospective cohort study using an electronic healthcare database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with AF from 2014 through 2018 and prescribed OACs were included and followed till December 31, 2019. Inverse probability of treatment weighting based on the propensity score (PS) is used to address potential bias due to nonrandomized allocation of treatment. The risks ofdiabetes were compared between different new OAC users using propensity score-weighted cumulative incidence differences (CID).

Results: There were 13,688 new users of OACs (warfarin: n = 3454; apixaban: n = 3335; dabigatran: n = 4210; rivaroxaban: n = 2689). The mean age was 75.0 (SD, 11.2), and 6,550 (47.9%) were women. After a median follow-up of 0.93 years (interquartile range, 0.21-1.92 years), 698 incident diabetes cases were observed. In Cox-regression analysis, dabigatran use was significantly associated with reduced risk of diabetes when compared with warfarin use [HR 0.69 (95% CI 0.56-0.86; P < 0.001)], with statistically insignificant associations observed for use of apixaban and rivaroxaban. The corresponding adjusted CIDs at 2 years after treatment with apixaban, dabigatran, and rivaroxaban users when compared with warfarin were - 2.06% (95% CI - 4.08 to 0.16%); - 3.06% (95% CI - 4.79 to - 1.15%); and - 1.8% (- 3.62 to 0.23%). In head-to-head comparisons between women DOAC users, dabigatran was also associated with a lower risk of diabetes when compared with apixaban and rivaroxaban.

Conclusions: Among adults with AF receiving OACs, the use of dabigatran had the lowest risk of diabetes when compared with warfarin use.
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http://dx.doi.org/10.1186/s12933-021-01263-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993481PMC
March 2021

Intramuscular midazolam, olanzapine, or haloperidol for the management of acute agitation: A multi-centre, double-blind, randomised clinical trial.

EClinicalMedicine 2021 Feb 11;32:100751. Epub 2021 Feb 11.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR.

Background: The safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated.

Methods: A pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18-75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam ( = 56), olanzapine ( = 54), or haloperidol ( = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118).

Findings: Of 206 patients randomised, 167 (mean age, 42 years; 98 [58·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8·5 (IQR 8·0), 11·5 (IQR 30·0), and 23·0 (IQR 21·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine ( = 0·03) and haloperidol ( = 0·002). Adverse event rates were similar across the three arms. Dystonia ( = 1) and cardiac arrest ( = 1) were reported in the haloperidol group.

Interpretation: Midazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects.

Funding: Research Grants Council, Hong Kong.
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http://dx.doi.org/10.1016/j.eclinm.2021.100751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910711PMC
February 2021

Cardiovascular sequalae in uncomplicated COVID-19 survivors.

PLoS One 2021 11;16(2):e0246732. Epub 2021 Feb 11.

Cardiology Division, Department of Medicine, the University of Hong Kong, Hong Kong SAR, China.

Background: A high proportion of COVID-19 patients were reported to have cardiac involvements. Data pertaining to cardiac sequalae is of urgent importance to define subsequent cardiac surveillance.

Methods: We performed a systematic cardiac screening for 97 consecutive COVID-19 survivors including electrocardiogram (ECG), echocardiography, serum troponin and NT-proBNP assay 1-4 weeks after hospital discharge. Treadmill exercise test and cardiac magnetic resonance imaging (CMR) were performed according to initial screening results.

Results: The mean age was 46.5 ± 18.6 years; 53.6% were men. All were classified with non-severe disease without overt cardiac manifestations and did not require intensive care. Median hospitalization stay was 17 days and median duration from discharge to screening was 11 days. Cardiac abnormalities were detected in 42.3% including sinus bradycardia (29.9%), newly detected T-wave abnormality (8.2%), elevated troponin level (6.2%), newly detected atrial fibrillation (1.0%), and newly detected left ventricular systolic dysfunction with elevated NT-proBNP level (1.0%). Significant sinus bradycardia with heart rate below 50 bpm was detected in 7.2% COVID-19 survivors, which appeared to be self-limiting and recovered over time. For COVID-19 survivors with persistent elevation of troponin level after discharge or newly detected T wave abnormality, echocardiography and CMR did not reveal any evidence of infarct, myocarditis, or left ventricular systolic dysfunction.

Conclusion: Cardiac abnormality is common amongst COVID-survivors with mild disease, which is mostly self-limiting. Nonetheless, cardiac surveillance in form of ECG and/or serum biomarkers may be advisable to detect more severe cardiac involvement including atrial fibrillation and left ventricular dysfunction.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246732PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877588PMC
February 2021

Comparative efficacy and safety of statin and fibrate monotherapy: A systematic review and meta-analysis of head-to-head randomized controlled trials.

PLoS One 2021 9;16(2):e0246480. Epub 2021 Feb 9.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Objective: To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates.

Methods: Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic.

Results: We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94-5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80-1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95-1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36-0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08-0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03-1.99, I2 = 44%; seven studies, n = 5225; low certainty).

Conclusions: The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246480PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872286PMC
July 2021

Hospitalization and Mortality in Patients With Heart Failure Treated With Sacubitril/Valsartan vs. Enalapril: A Real-World, Population-Based Study.

Front Cardiovasc Med 2020 20;7:602363. Epub 2021 Jan 20.

Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, Centre for Safe Medication Practice and Research, University of Hong Kong, Hong Kong, China.

The effect of sacubitril/valsartan on survival and hospitalization risk in older patients with heart failure has not been explored. We aimed to investigate the risk of hospitalization and mortality with the use of sacubitril/valsartan vs. enalapril in patients with heart failure. This was a population-based cohort study using the Hong Kong-wide electronic healthcare database. Patients diagnosed with heart failure and newly prescribed sacubitril/valsartan or enalapril between July 2016 and June 2019 were included. The risk of primary composite outcome of cardiovascular mortality or heart failure-related hospitalization, all-cause hospitalization, heart failure-related hospitalization, cardiovascular mortality and all-cause mortality were compared using Cox regression with inverse probability treatment weighting. Additional analysis was conducted by age stratification. Of the 44,503 patients who received sacubitril/valsartan or enalapril, 3,237 new users (sacubitril/valsartan, = 1,056; enalapril, = 2,181) with a diagnosis of heart failure were identified. Compared with enalapril, sacubitril/valsartan users were associated with a lower risk of primary composite outcome [hazard ratio (HR) 0.58; 95% confidence interval (CI), 0.45-0.75], heart failure-related hospitalization (HR 0.59; 95% CI, 0.45-0.77), all-cause mortality (HR 0.51; 95% CI, 0.36-0.74) and borderline non-significant reductions in all-cause hospitalization (HR 0.85; 95% CI, 0.70-1.04) and cardiovascular mortality (HR 0.63; 95% CI, 0.39-1.02). The treatment effect of sacubitril/valsartan remains unaltered in the patient subgroup age ≥ 65 years (73%). In real-world settings, sacubitril/valsartan was associated with improved survival and reduced heart failure-related hospitalization compared to enalapril in Asian patients with heart failure. The effectiveness remains consistent in the older population.
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http://dx.doi.org/10.3389/fcvm.2020.602363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855850PMC
January 2021

Data-driven identification of ageing-related diseases from electronic health records.

Sci Rep 2021 Feb 3;11(1):2938. Epub 2021 Feb 3.

Health Data Research UK London, University College London, London, UK.

Reducing the burden of late-life morbidity requires an understanding of the mechanisms of ageing-related diseases (ARDs), defined as diseases that accumulate with increasing age. This has been hampered by the lack of formal criteria to identify ARDs. Here, we present a framework to identify ARDs using two complementary methods consisting of unsupervised machine learning and actuarial techniques, which we applied to electronic health records (EHRs) from 3,009,048 individuals in England using primary care data from the Clinical Practice Research Datalink (CPRD) linked to the Hospital Episode Statistics admitted patient care dataset between 1 April 2010 and 31 March 2015 (mean age 49.7 years (s.d. 18.6), 51% female, 70% white ethnicity). We grouped 278 high-burden diseases into nine main clusters according to their patterns of disease onset, using a hierarchical agglomerative clustering algorithm. Four of these clusters, encompassing 207 diseases spanning diverse organ systems and clinical specialties, had rates of disease onset that clearly increased with chronological age. However, the ages of onset for these four clusters were strikingly different, with median age of onset 82 years (IQR 82-83) for Cluster 1, 77 years (IQR 75-77) for Cluster 2, 69 years (IQR 66-71) for Cluster 3 and 57 years (IQR 54-59) for Cluster 4. Fitting to ageing-related actuarial models confirmed that the vast majority of these 207 diseases had a high probability of being ageing-related. Cardiovascular diseases and cancers were highly represented, while benign neoplastic, skin and psychiatric conditions were largely absent from the four ageing-related clusters. Our framework identifies and clusters ARDs and can form the basis for fundamental and translational research into ageing pathways.
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http://dx.doi.org/10.1038/s41598-021-82459-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859412PMC
February 2021

Impact of multiple cardiovascular medications on mortality after an incidence of ischemic stroke or transient ischemic attack.

BMC Med 2021 02 3;19(1):24. Epub 2021 Feb 3.

Research Department of Practice and Policy, School of Pharmacy, University College London, London, UK.

Background: To manage the risk factors and to improve clinical outcomes, patients with stroke commonly receive multiple cardiovascular medications. However, there is a lack of evidence on the optimum combination of medication therapy in the primary care setting after ischemic stroke. Therefore, this study aimed to investigate the effect of multiple cardiovascular medications on long-term survival after an incident stroke event (ischemic stroke or transient ischemic attack (TIA)).

Methods: This study consisted of 52,619 patients aged 45 and above with an incident stroke event between 2007 and 2016 in The Health Improvement Network database. We estimated the risk of all-cause mortality in patients with multiple cardiovascular medications versus monotherapy using a marginal structural model.

Results: During an average follow-up of 3.6 years, there were 9230 deaths (7635 in multiple cardiovascular medication groups and 1595 in the monotherapy group). Compared with patients prescribed monotherapy only, the HRs of mortality were 0.82 (95% CI 0.75-0.89) for two medications, 0.65 (0.59-0.70) for three medications, 0.61 (0.56-0.67) for four medications, 0.60 (0.54-0.66) for five medications and 0.66 (0.59-0.74) for ≥ six medications. Patients with any four classes of antiplatelet agents (APAs), lipid-regulating medications (LRMs), angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), beta-blockers, diuretics and calcium channel blockers (CCBs) had the lowest risk of mortality (HR 0.51, 95% CI 0.46-0.57) versus any one class. The combination containing APAs, LRMs, ACEIs/ARBs and CCBs was associated with a 61% (95% CI 53-68%) lower risk of mortality compared with APAs alone.

Conclusion: Our results suggested that combination therapy of four or five cardiovascular medications may be optimal to improve long-term survival after incident ischemic stroke or TIA. APAs, LRMs, ACEIs/ARBs and CCBs were the optimal constituents of combination therapy in the present study.
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http://dx.doi.org/10.1186/s12916-021-01900-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856718PMC
February 2021

Saliva viral load better correlates with clinical and immunological profiles in children with coronavirus disease 2019.

Emerg Microbes Infect 2021 Dec;10(1):235-241

Paediatric Infectious Disease Unit, Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong SAR, People's Republic of China.

Background: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking.

Methods: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19.

Findings: 91 patients were included between March and August 20 20. NPS and saliva viral loads were correlated ( = 0.315,  = 0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log NPS ( = -0.532,  < 0.001) and saliva ( = -0.417,  < 0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all  < 0.05), and were inversely correlated with total lymphocyte ( = -0.43), CD3 ( = -0.55), CD4 ( = -0.60), CD8 ( = -0.41), B ( = -0.482), and NK ( = -0.416) lymphocyte counts (all  < 0.05).

Interpretation: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS.
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http://dx.doi.org/10.1080/22221751.2021.1878937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899683PMC
December 2021
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