Publications by authors named "Eric Yuk Fai Wan"

76 Publications

The Spill-Over Impact of the Novel Coronavirus-19 Pandemic on Medical Care and Disease Outcomes in Non-communicable Diseases: A Narrative Review.

Public Health Rev 2022 27;43:1604121. Epub 2022 Apr 27.

Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.

The coronavirus-19 (COVID-19) pandemic has claimed more than 5 million lives worldwide by November 2021. Implementation of lockdown measures, reallocation of medical resources, compounded by the reluctance to seek help, makes it exceptionally challenging for people with non-communicable diseases (NCD) to manage their diseases. This review evaluates the spill-over impact of the COVID-19 pandemic on people with NCDs including cardiovascular diseases, cancer, diabetes mellitus, chronic respiratory disease, chronic kidney disease, dementia, mental health disorders, and musculoskeletal disorders. Literature published in English was identified from PubMed and medRxiv from January 1, 2019 to November 30, 2020. A total of 119 articles were selected from 6,546 publications found. The reduction of in-person care, screening procedures, delays in diagnosis, treatment, and social distancing policies have unanimously led to undesirable impacts on both physical and psychological health of NCD patients. This is projected to contribute to more excess deaths in the future. The spill-over impact of COVID-19 on patients with NCD is just beginning to unravel, extra efforts must be taken for planning the resumption of NCD healthcare services post-pandemic.
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http://dx.doi.org/10.3389/phrs.2022.1604121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091177PMC
April 2022

Identifying and articulating the student experience in the Intercalated Enrichment Year.

BMC Med Educ 2022 Apr 4;22(1):246. Epub 2022 Apr 4.

Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 3/F Ap Lei Chau Clinic, 161 Main Street, Ap Lei Chau, Hong Kong SAR, China.

Background: Benefits of intercalation during an undergraduate medical degree are well-recognized. The University of Hong Kong implemented a compulsory Enrichment Year (EY) in its Bachelor of Medicine and Bachelor of Surgery degree programme (MBBS) in 2016. In their third year of study, students could work on an area of interest in any of three programme categories (i) intercalation/ university exchange (IC); (ii) research (RA); (iii) service/ humanitarian work (SH). This study aimed to explore the barriers, enablers, and overall student learning experiences from the first cohort of EY students in order to inform future development of the EY.

Methods: An exploratory sequential mixed-method study in 2019-20. Twenty students were purposively selected to attend three semi-structured focus group interviews. Conventional thematic analysis was employed and results assisted the design of a cross-sectional questionnaire. Sixty-three students completed the questionnaire. ANOVA or chi-square test was used to compare the difference in student's characteristics, barriers, enablers and perspectives on EY between programme categories. Adjusting student's characteristics, logistic regressions were conducted to identify the effect of programme categories on the EY experience.

Results: Most students (95% in the questionnaire) agreed that EY was worthwhile and more rewarding than expected. EY was positively regarded for enhancing personal growth and interpersonal relationships. The main barriers were financial difficulties, scholarship issues and insufficient information beforehand. A few students had practical (i.e. accommodation, cultural adaptation) problems. Potential enablers included better financial support, more efficient information exchange and fewer assignments and preparation tasks. Similar barriers were encountered by students across all three categories of EY activities.

Conclusions: Personal growth was the most important benefit of the EY. Barriers were consistent with those identified in the literature except for cultural adaptation, which could be related to Hong Kong's unique historical context. Financial limitation was the most concerning barrier, as it could result in unequal access to educational opportunities. Better and timely access to scholarships and other funding sources need to be considered.

Trial Registration: Ethics approval was obtained from the local Institutional Review Board of The University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 19-585 ).
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http://dx.doi.org/10.1186/s12909-022-03303-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981939PMC
April 2022

Impact of a delayed second dose of mRNA vaccine (BNT162b2) and inactivated SARS-CoV-2 vaccine (CoronaVac) on risks of all-cause mortality, emergency department visit, and unscheduled hospitalization.

BMC Med 2022 03 17;20(1):119. Epub 2022 Mar 17.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong SAR, China.

Background: Safety after the second dose of the SARS-CoV-2 vaccine remains to be elucidated, especially among individuals reporting adverse events after their first dose. This study aims to evaluate the impact of a delayed second dose on all-cause mortality and emergency services.

Methods: A territory-wide, retrospective cohort of people who had completed two doses of mRNA (BNT162b2) or inactivated SARS-CoV-2 (CoronaVac) vaccine between February 23 and July 3, 2021, in Hong Kong was analyzed, with linkage to electronic health records retrieved from the Hong Kong Hospital Authority. Vaccine recipients were classified as receiving a second dose within recommended intervals (21-28 days for BNT162b2; 14-28 days for CoronaVac) or delayed. Study outcomes were all-cause mortality, emergency department (ED) visits, and unscheduled hospitalizations within 28 days after the second dose of vaccination.

Results: Among 417,497 BNT162b2 and 354,283 CoronaVac second dose recipients, 3.8% and 28.5% received the second dose beyond the recommended intervals (mean 34.4 and 31.8 days), respectively. During the study period, there were < 5 daily new cases of COVID-19 infections in the community. Delaying the second dose was not associated with all-cause mortality (hazard ratio [HR] = 1.185, 95% CI 0.478-2.937, P = 0.714), risk of ED visit (HR = 0.966, 95% CI 0.926-1.008, P = 0.113), and risk of unscheduled hospitalization (HR = 0.956, 95% CI 0.878-1.040, P = 0.294) compared to that within the recommended interval for CoronaVac recipients. No statistically significant differences in all-cause mortality (HR = 4.438, 95% CI 0.951-20.701, P = 0.058), ED visit (HR = 1.037, 95% CI 0.951-1.130, P = 0.411), and unscheduled hospitalization (HR = 1.054, 95% CI 0.867-1.281, P = 0.597) were identified between people who received a second dose of BNT162b2 within and beyond the recommended intervals.

Conclusions: No significant association between delayed second dose of BNT162b2 or CoronaVac and all-cause mortality, ED visit, and unscheduled hospitalization was observed in the present cohort. Regardless of the recommended or delayed schedule for SARS-CoV-2 vaccination, a second dose of both vaccines should be administered to obtain better protection against infection and serious disease. The second dose should be administered within the recommended interval following the manufacturer's product information, until further studies support the benefits of delaying vaccination outweighing the risks.
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http://dx.doi.org/10.1186/s12916-022-02321-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8926447PMC
March 2022

Association Between Team-Based Continuity of Care and Risk of Cardiovascular Diseases Among Patients With Diabetes: A Retrospective Cohort Study.

Diabetes Care 2022 May;45(5):1162-1169

Department of Family Medicine and Primary Care, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Objective: Cardiovascular diseases (CVD) are a long-term sequela of diabetes. Better individual-based continuity of care has been reported to reduce the risk of chronic complications among patients with diabetes. Maintaining a one-to-one patient-physician relationship is often challenging, especially in public health care settings. This study aimed to evaluate the relationship between higher team-based continuity of care, defined as consultations provided by the same physician team, and CVD risks in patients with diabetes from public primary care clinics.

Research Design And Methods: This was a retrospective cohort study in Hong Kong of 312,068 patients with type 2 diabetes and without any history of CVD at baseline (defined as the earliest attendance at a doctor's consultation in a public-sector clinic between 2008 and 2018). Team-based continuity of care was measured using the usual provider continuity index (UPCI), calculated by the proportion of consultations provided by the most visited physician team in the 2 years before baseline. Patients were divided into quartiles based on their UPCI, and the characteristics of the quartiles were balanced using propensity score fine stratification weights. Multivariable Cox regression was applied to assess the effect of team-based continuity of care on CVD incidence. Patient demographics, smoking status, physiological measurements, number of attendances, comorbidities, and medications were adjusted for in the propensity weightings and regression analyses.

Results: After an average follow-up of 6.5 years, the total number of new CVD events was 52,428. Compared with patients in the 1st quartile, patients in the 2nd, 3rd, and 4th quartiles of the UCPI had a CVD hazard ratio (95% CI) of 0.95 (0.92-0.97), 0.92 (0.89-0.94), and 0.87 (0.84-0.89), respectively, indicating that higher continuity of care was associated with lower CVD risks. The subtypes of CVD, including coronary heart disease and stroke, also showed a similar pattern. Subgroup analyses suggested that patients <65 years of age had greater benefits from higher team-based continuity of care.

Conclusions: Team-based continuity of care was associated with lower CVD risk among individuals with type 2 diabetes, especially those who were younger. This suggests a potential flexible alternative implementation of continuity of care in public clinics.
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http://dx.doi.org/10.2337/dc21-1217DOI Listing
May 2022

Adverse events of special interest following the use of BNT162b2 in adolescents: a population-based retrospective cohort study.

Emerg Microbes Infect 2022 Dec;11(1):885-893

Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China.

Accruing evidence suggests an increased risk of myocarditis in adolescents from messenger RNA COVID-19 vaccines. However, other potential adverse events remain under-researched. We conducted a retrospective cohort study of adolescents aged 12-18 with a territory-wide electronic healthcare database of the Hong Kong population linked with population-based vaccination records and supplemented with age- and sex-specific population numbers. Two age- and sex-matched retrospective cohorts were formed to observe 28 days following the first and second doses of BNT162b2 and estimate the age- and sex-adjusted incidence rate ratios between the vaccinated and unvaccinated. Thirty AESIs adapted from the World Health Organization's Global Advisory Committee on Vaccine Safety were examined. Eventually, the first-dose cohort comprised 274,881 adolescents (50.25% received the first dose) and the second-dose cohort 237,964 (50.29% received the second dose). Ninety-four (34.2 per 100,000 persons) adolescents in the first-dose cohort and 130 (54.6 per 100,000 persons) in the second-dose cohort experienced ≥1 AESIs. There were no statistically significant differences in the risk of any AESI associated with BNT162b2 except myocarditis [first-dose cohort: incidence rate ratio (IRR) = 9.15, 95% confidence interval (CI) 1.14-73.16; second-dose cohort: IRR = 29.61, 95% CI 4.04-217.07] and sleeping disturbances/disorders after the second dose (IRR = 2.06, 95% CI 1.01-4.24). Sensitivity analysis showed that, with myocarditis excluded as AESIs, no significantly elevated risk of AESIs as a composite outcome associated with vaccination was observed (= 0.195). To conclude, the overall absolute risk of AESIs was low with no evidence of an increased risk of AESIs except myocarditis and sleeping disturbances/disorders.
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http://dx.doi.org/10.1080/22221751.2022.2050952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8942549PMC
December 2022

Safety of Inactivated and mRNA COVID-19 Vaccination Among Patients Treated for Hypothyroidism: A Population-Based Cohort Study.

Thyroid 2022 May 7;32(5):505-514. Epub 2022 Apr 7.

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.

Thyroiditis and Graves' disease have been reported after coronavirus disease 2019 (COVID-19) vaccination. We evaluated the risks of adverse events after COVID-19 vaccination among patients treated for hypothyroidism. In this retrospective population-based cohort study of Hong Kong Hospital Authority electronic health records with the Department of Health vaccination records linkage, levothyroxine (LT4) users were categorized into unvaccinated, vaccinated with BNT162b2 (mRNA vaccine), or CoronaVac (inactivated vaccine) between February 23, 2021, and September 9, 2021. Study outcomes were dosage reduction or escalation in LT4, emergency department (ED) visit, unscheduled hospitalization, adverse events of special interest (AESI) according to the World Health Organization's Global Advisory Committee on Vaccine Safety, and all-cause mortality. Inverse probability of treatment weighting for propensity score was applied to balance baseline patient characteristics among the three groups. Hazard ratios (HR) were estimated using Cox regression models. Patients were observed from the index date until the occurrence of study outcome, death, or censored on September 30, 2021, whichever came first. In total, 47,086 LT4 users were identified (BNT162b2:  = 12,310; CoronaVac:  = 11,353; and unvaccinated:  = 23,423). COVID-19 vaccination was not associated with increased risks of LT4 dosage reduction (BNT162b2: HR = 0.971 [confidence interval; CI 0.892-1.058]; CoronaVac: HR = 0.968 [CI 0.904-1.037]) or escalation (BNT162b2: HR = 0.779 [CI 0.519-1.169]; CoronaVac: HR = 0.715 [CI 0.481-1.062]). Besides, COVID-19 vaccination was not associated with a higher risk of ED visits (BNT162b2: HR = 0.944 [CI 0.700-1.273]; CoronaVac: HR = 0.851 [CI 0.647-1.120]) or unscheduled hospitalization (BNT162b2: HR = 0.905 [CI 0.539-1.520]; CoronaVac: HR = 0.735 [CI 0.448-1.207]). There were two (0.016%) deaths and six (0.062%) AESI recorded for BNT162b2 recipients, and one (0.009%) and three (0.035%) for CoronaVac recipients, respectively. BNT162b2 or CoronaVac vaccination is not associated with unstable thyroid status or an increased risk of adverse outcomes among patients treated for hypothyroidism in general. These reassuring data should encourage them to get vaccinated against COVID-19 for protection from potentially worse COVID-19-related outcomes.
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http://dx.doi.org/10.1089/thy.2021.0684DOI Listing
May 2022

Self-reported reactogenicity of CoronaVac (Sinovac) compared with Comirnaty (Pfizer-BioNTech): A prospective cohort study with intensive monitoring.

Vaccine 2022 03 7;40(10):1390-1396. Epub 2022 Feb 7.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China; Laboratory of Data Discovery for. Health (D(2)4H), Hong Kong Science and Technology Park, Hong Kong, China. Electronic address:

Objective: CoronaVac (Sinovac) Covid-19 vaccine has recently been approved for emergency use by the World Health Organization. However, data on its reactogenicity in real-world settings is scant. This study aimed to compare self-reported post-vaccination adverse reactions between CoronaVac and Comirnaty (Pfizer-BioNTech).

Methods: We adopted a prospective cohort study design using online surveys from the day of first-dose vaccination with intensive follow-up through two weeks after the second dose (11 time points). The primary outcome was adverse reactions (any versus none) and secondary outcomes were the sub-categories of adverse reactions (local, systemic, and severe allergic reactions). Potential effect modification across multimorbidity status, older age, and sex was examined.

Results: In total, 2,098 participants who were scheduled to complete the 14th-day survey were included, with 46.2% receiving Comirnaty. Retention rate two weeks after the second dose was 81.0% for the CoronaVac group and 83.6% for the Comirnaty group. Throughout the follow-up period, 801 (82.7%) of those receiving Comirnaty and 543 (48.1%) of those receiving CoronaVac reported adverse reactions. Adjusted analysis suggested that compared with Comirnaty, CoronaVac was associated with 83%-reduced odds of any adverse reactions [adjusted odds ratio (AOR) = 0.17, 95% confidence interval (CI) 0.15-0.20], 92%-reduced odds of local adverse reactions (AOR = 0.08, 95% CI 0.06-0.09), and 76%-reduced odds of systemic adverse reactions (AOR = 0.24, 95% CI 0.16-0.28). No significant effect modification was identified.

Conclusion: This post-marketing study comparing the reactogenicity of Covid-19 vaccines suggests a lower risk of self-reported adverse reactions following vaccination with CoronaVac compared with Comirnaty.
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http://dx.doi.org/10.1016/j.vaccine.2022.01.062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818394PMC
March 2022

Lack of inflammatory bowel disease flare-up following two-dose BNT162b2 vaccine: a population-based cohort study.

Gut 2022 Feb 8. Epub 2022 Feb 8.

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 Special Administrative Region, People's Republic of China

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http://dx.doi.org/10.1136/gutjnl-2021-326860DOI Listing
February 2022

Herpes zoster related hospitalization after inactivated (CoronaVac) and mRNA (BNT162b2) SARS-CoV-2 vaccination: A self-controlled case series and nested case-control study.

Lancet Reg Health West Pac 2022 Apr 2;21:100393. Epub 2022 Feb 2.

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 Special Administrative Region, China.

Background: Stimulation of immunity by vaccination may elicit adverse events. There is currently inconclusive evidence on the relationship between herpes zoster related hospitalization and COVID-19 vaccination. This study aimed to evaluate the effect of inactivated virus (CoronaVac, Sinovac) and mRNA (BNT162b2, BioNTech/Fosun Pharma) COVID-19 vaccine on the risk of herpes zoster related hospitalization.

Methods: Self-controlled case series (SCCS) analysis was conducted using the data from the electronic health records in Hospital Authority and COVID-19 vaccination records in the Department of Health in Hong Kong. We conducted the SCCS analysis including patients with a first primary diagnosis of herpes zoster in the hospital inpatient setting between February 23 and July 31, 2021. A confirmatory analysis by nested case-control method was also conducted. Each herpes zoster case was randomly matched with ten controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Conditional Poisson regression and logistic regression models were used to assess the potential excess rates of herpes zoster after vaccination.

Findings: From February 23 to July 31, 2021, a total of 16 and 27 patients were identified with a first primary hospital diagnosis of herpes zoster within 28 days after CoronaVac and BNT162b2 vaccinations. The incidence of herpes zoster was 7.9 (95% Confidence interval [CI]: 5.2-11.5) for CoronaVac and 7.1 (95% CI: 4.1-11.5) for BNT162b2 per 1,000,000 doses administered. In SCCS analysis, CoronaVac vaccination was associated with significantly higher risk of herpes zoster within 14 days after first dose (adjusted incidence rate ratio [aIRR]=2.67, 95% CI: 1.08-6.59) but not in other periods afterwards compared to the baseline period. Regarding BNT162b2 vaccination, a significantly increased risk of herpes zoster was observed after first dose up to 14 days after second dose (0-13 days after first dose: aIRR=5.23, 95% CI: 1.61-17.03; 14-27 days after first dose: aIRR=5.82, 95% CI: 1.62-20.91; 0-13 days after second dose: aIRR=5.14, 95% CI: 1.29-20.47). Using these relative rates, we estimated that there has been an excess of approximately 5 and 7 cases of hospitalization as a result of herpes zoster after every 1,000,000 doses of CoronaVac and BNT162b2 vaccination, respectively. The findings in the nested case control analysis showed similar results.

Interpretation: We identified an increased risk of herpes zoster related hospitalization after CoronaVac and BNT162b2 vaccinations. However, the absolute risks of such adverse event after CoronaVac and BNT162b2 vaccinations were very low. In locations where COVID-19 is prevalent, the protective effects on COVID-19 from vaccinations will greatly outweigh the potential side effects of vaccination.

Funding: The project was funded by Research Grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref. No.COVID19F01). FTTL (Francisco Tsz Tsun Lai) and ICKW (Ian Chi Kei Wong)'s posts were partly funded by D4H; hence this work was partly supported by [email protected] administered by Innovation and Technology Commission.
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http://dx.doi.org/10.1016/j.lanwpc.2022.100393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808060PMC
April 2022

Safety and effectiveness of low-dose aspirin for the prevention of gastrointestinal cancer in adults without atherosclerotic cardiovascular disease: a population-based cohort study.

BMJ Open 2022 02 4;12(2):e050510. Epub 2022 Feb 4.

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

Objective: To assess the association between low-dose aspirin and the incidence of colorectal cancer (CRC), gastric cancer (GC), oesophageal cancer (EC) and gastrointestinal bleeding (GIB) in adults without established atherosclerotic cardiovascular disease.

Design: Cohort study with propensity score matching of new-users of aspirin to non-users.

Setting: Clinical Data Analysis and Reporting System database, Hong Kong.

Participants: Adults ≥40 years with a prescription start date of either low-dose aspirin (75-300 mg/daily) or paracetamol (non-aspirin users) between 1 January 2004 to 31 December 2008 without a history of atherosclerotic cardiovascular disease.

Main Outcome Measures: The primary outcome was the first diagnosis of gastrointestinal cancer (either CRC, GC or EC) and the secondary outcome was GIB. Individuals were followed from index date of prescription until the earliest occurrence of an outcome of interest, an incident diagnosis of any type of cancer besides the outcome, death or until 31 December 2017. A competing risk survival analysis was used to estimate HRs and 95% CIs with death as the competing risk.

Results: After matching, 49 679 aspirin and non-aspirin users were included. The median (IQR) follow-up was 10.0 (6.4) years. HRs for low-dose aspirin compared with non-aspirin users were 0.83 for CRC (95% CI, 0.76 to 0.91), 0.77 for GC (95% CI, 0.65 to 0.92) and 0.88 for EC (95% CI, 0.67 to 1.16). Patients prescribed low-dose aspirin had an increased risk of GIB (HR 1.15, 95% CI, 1.11 to 1.20), except for patients prescribed proton pump inhibitors or histamine H2-receptor antagonists (HR 1.03, 95% CI, 0.96 to 1.10).

Conclusion: In this cohort study of Chinese adults, patients prescribed low-dose aspirin had reduced risks of CRC and GC and an increased risk of GIB. Among the subgroup of patients prescribed gastroprotective agents at baseline, however, the association with GIB was attenuated.
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http://dx.doi.org/10.1136/bmjopen-2021-050510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819826PMC
February 2022

The association between trajectories of risk factors and risk of cardiovascular disease or mortality among patients with diabetes or hypertension: A systematic review.

PLoS One 2022 27;17(1):e0262885. Epub 2022 Jan 27.

Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Introduction: Cardiometabolic risk factors and renal function are monitored regularly for patients with diabetes mellitus (DM)/ hypertension (HT). In addition to risk factor levels at a single time point, their trajectory (changes over time) can also be differentially related to the risk of cardiovascular diseases (CVD) and mortality. This study aimed to systematically examine the evidence regarding the association between risk factor trajectories and risk of CVD/mortality in patients with DM/HT.

Method: PubMed, MEDLINE, and Embase were searched for articles from January 1963 to April 2021. Inclusion criteria: studies that 1) analyzed trajectories of risk factors including haemoglobin A1c (HbA1c), blood pressure, estimated glomerular filtration rate (eGFR), body mass index (BMI), and blood lipids; 2) were performed in the DM/HT population and, 3) included risk of CVD/mortality as outcomes. Study quality was assessed using the Newcastle-Ottawa quality assessment scale.

Results: A total of 22,099 articles were identified. After screening by title and abstract, 22,027 articles were excluded by irrelevant outcomes, exposure, population, or type of articles. Following full-text screening, 11 articles investigating the trajectories of HbA1c (N = 7), systolic blood pressure (SBP) (N = 3), and eGFR (N = 1) were included for data extraction and analysis. No studies were identified examining the association of BMI or lipid trajectories with CVD/mortality. All included studies were of good quality based on the NOS criteria. In general, stable trajectories within optimal ranges of the risk factors (HbA1c: <7%, SBP: 120-139mmHg, eGFR: >60mL/min/1.73m2) had the lowest CVD/mortality risk compared to an increasing HbA1c trajectory (from 8% to 10%), an increasing SBP trajectory (from 120-139 to ≥140mmHg), or a decreasing eGFR trajectory (from 90 to 70mL/min/1.73m2).

Conclusion: A relatively stable and well-controlled trajectory for cardiometabolic risk factors was associated with the lowest risk of CVD/mortality. Risk factor trajectories have important clinical implications in addition to single time point measurements. More attention should be given to patients with suboptimal control and those with unstable trends of cardiometabolic risk factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262885PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794125PMC
February 2022

COVID-19 vaccines and risks of hematological abnormalities: Nested case-control and self-controlled case series study.

Am J Hematol 2022 04 9;97(4):470-480. Epub 2022 Feb 9.

Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong Special Administrative Region, China.

Several studies reported hematological abnormalities after vaccination against the coronavirus disease 2019 (COVID-19). We evaluated the association between COVID-19 vaccines (CoronaVac and BNT162b2) and hematological abnormalities. We conducted nested case-control and self-controlled case series analyses using the data from the Hong Kong Hospital Authority and the Department of Health, HKSAR. Outcomes of interest were thrombocytopenia, leukopenia, and neutropenia. Adjusted odds ratios (aORs), incidence rate ratios (IRRs), and 95% confidence intervals (CIs) were estimated using conditional logistic regression. In total, 1 643 419 people received COVID-19 vaccination (738 609 CoronaVac; 904 810 BNT162b2). We identified 457 and 422 cases after CoronaVac and BNT162b2 vaccination, respectively. For CoronaVac, the incidence of thrombocytopenia, leukopenia, and neutropenia was 2.51, 1.08, and 0.15 per 10 000 doses. For BNT162b2, the corresponding incidence was 1.39, 1.17, and 0.26 per 10 000 doses. The incidence per 10 000 COVID-19 cases were 1254, 2341, and 884, respectively. We only observed an increased risk of leukopenia following the second dose of BNT162b2 (aOR 1.58, 95% CI 1.24-2.02; day 0-14, IRR 2.21; 95% CI 1.59-3.08). There was no increased risk of any hematological abnormalities after CoronaVac vaccination. We observed an increased risk of leukopenia shortly after the second dose of BNT162b2. However, the incidence was much lower than the incidence following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. There was no association between CoronaVac and hematological abnormalities. The benefits of vaccination against COVID-19 still outweigh the risk of hematological abnormalities.
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http://dx.doi.org/10.1002/ajh.26478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9011752PMC
April 2022

Carditis After COVID-19 Vaccination With a Messenger RNA Vaccine and an Inactivated Virus Vaccine : A Case-Control Study.

Ann Intern Med 2022 03 25;175(3):362-370. Epub 2022 Jan 25.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, and Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China, and Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom (I.C.K.).

Background: Case reports of carditis after BNT162b2 vaccination are accruing worldwide.

Objective: To examine the association of BNT162b2 and CoronaVac (Sinovac) vaccination with carditis.

Design: Case-control study with hospital control participants.

Setting: Territory-wide, public health care database with linkage to population-based vaccination records in Hong Kong.

Patients: Inpatients aged 12 years or older first diagnosed with carditis were selected as case patients. All other hospitalized patients without carditis were treated as control participants. Ten control participants were randomly matched with each case patient by age, sex, and admission date.

Intervention: Vaccination with BNT162b2 or CoronaVac.

Measurements: Incident diagnosis of carditis based on the International Classification of Diseases, Ninth Revision, and elevated troponin levels.

Results: A total of 160 case patients and 1533 control participants were included. Incidence of carditis per 100 000 doses of CoronaVac and BNT162b2 administered was estimated to be 0.31 (95% CI, 0.13 to 0.66) and 0.57 (CI, 0.36 to 0.90), respectively. Multivariable analyses showed that recipients of the BNT162b2 vaccine had higher odds of carditis (adjusted odds ratio [OR], 3.57 [CI, 1.93 to 6.60]) than unvaccinated persons. Stratified by sex, the OR was 4.68 (CI, 2.25 to 9.71) for males and 2.22 (CI, 0.57 to 8.69) for females receiving the BNT162b2 vaccine. The ORs for adults and adolescents receiving the BNT162b2 vaccine were 2.41 (CI, 1.18 to 4.90) and 13.79 (CI, 2.86 to 110.38), respectively. Subanalysis showed an OR of 9.29 (CI, 3.94 to 21.91) for myocarditis and 1.06 (CI, 0.35 to 3.22) for pericarditis associated with BNT162b2. The risk was mainly seen after the second dose of BNT162b2 rather than the first. No association between CoronaVac and carditis with a magnitude similar to that for BNT162b2 was seen.

Limitation: Limited sample size, absence of electrocardiography and other clinical investigative data, and unrecorded overseas vaccination exposure.

Conclusion: Despite a low absolute risk, there is an increased risk for carditis associated with BNT162b2 vaccination. This elevated risk should be weighed against the benefits of vaccination.

Primary Funding Source: Health and Medical Research Fund.
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http://dx.doi.org/10.7326/M21-3700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814917PMC
March 2022

Multimorbidity and adverse events of special interest associated with Covid-19 vaccines in Hong Kong.

Nat Commun 2022 01 20;13(1):411. Epub 2022 Jan 20.

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 Special Administrative Region, China.

Prior research using electronic health records for Covid-19 vaccine safety monitoring typically focuses on specific disease groups and excludes individuals with multimorbidity, defined as ≥2 chronic conditions. We examine the potential additional risk of adverse events 28 days after the first dose of CoronaVac or Comirnaty imposed by multimorbidity. Using a territory-wide public healthcare database with population-based vaccination records in Hong Kong, we analyze a retrospective cohort of patients with chronic conditions. Thirty adverse events of special interest according to the World Health Organization are examined. In total, 883,416 patients are included and 2,807 (0.3%) develop adverse events. Results suggest vaccinated patients have lower risks of adverse events than unvaccinated individuals, multimorbidity is associated with increased risks regardless of vaccination, and the association of vaccination with adverse events is not modified by multimorbidity. To conclude, we find no evidence that multimorbidity imposes extra risks of adverse events following Covid-19 vaccination.
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http://dx.doi.org/10.1038/s41467-022-28068-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776841PMC
January 2022

Post-Covid-19-vaccination adverse events and healthcare utilization among individuals with or without previous SARS-CoV-2 infection.

J Intern Med 2022 Jun 1;291(6):864-869. Epub 2022 Feb 1.

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.

Background: Post-marketing pharmacovigilance data are scant on the safety of Covid-19 vaccines among people with previous SARS-CoV-2 infection compared with ordinary vaccine recipients. We compared the post-vaccination adverse events of special interests (AESI), accident and emergency room (A&E) visit, and hospitalization between these two groups.

Methods: We conducted a retrospective cohort study using a territory-wide public healthcare database with population-based vaccination records in Hong Kong.

Results: In total, 3922 vaccine recipients with previous SARS-CoV-2 infection and 1,137,583 vaccine recipients without previous SARS-CoV-2 infection were included. No significant association was observed between previous SARS-CoV-2 infection and AESI or hospitalization. Previous SARS-CoV-2 infection was significantly associated with a lower risk of A&E visit (CoronaVac: hazard ratios [HR] = 0.56, 95% confidence intervals [CI]: 0.32-0.99; Comirnaty: HR = 0.62, 95% CI: 0.47-0.82).

Conclusion: No safety signal of Covid-19 vaccination was detected from the comparison between vaccine recipients with previous SARS-CoV-2 infection and those without infection.
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http://dx.doi.org/10.1111/joim.13453DOI Listing
June 2022

Comparing self-reported reactogenicity between adolescents and adults following the use of BNT162b2 (Pfizer-BioNTech) messenger RNA COVID-19 vaccine: a prospective cohort study.

Int J Infect Dis 2022 Mar 26;116:47-50. Epub 2021 Dec 26.

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China; Laboratory of Data Discovery for Health (D²4H), Hong Kong Science and Technology Park, Hong Kong, China. Electronic address:

Objectives: Although clinical data have shown that the BNT162b2 vaccine, which is widely used in many countries, is safe and effective as a protection against the SARS-CoV-2 infection, extant research in adverse reactions using real-world data of various sociodemographic characteristics is scant.

Methods: We conducted a prospective cohort study to compare age differences in self-reported reactogenicity of BNT162b2 in Hong Kong. A total of 1,516 participants were intensively followed up for two weeks following both doses of BNT162b2 vaccination, during which their basic demographic, health conditions, and medication information were collected.

Results: Results from the generalized mixed model showed that compared with adults aged 18 to 59 years, older adults aged 60 years or above had a lower risk of adverse reactions and adolescents aged 12 to 17 years had a moderately higher risk.

Conclusions: Results of this study should be informative to parents considering BNT162b2 vaccination for their children in that moderately increased reactogenicity compared with adults is anticipated.
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http://dx.doi.org/10.1016/j.ijid.2021.12.354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710238PMC
March 2022

Adverse event reporting and Bell's palsy risk after COVID-19 vaccination - Authors' reply.

Lancet Infect Dis 2021 11;21(11):1492-1493

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong SAR, China; Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Sha Tin, Hong Kong SAR, China.

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http://dx.doi.org/10.1016/S1473-3099(21)00631-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550904PMC
November 2021

Two-dose COVID-19 vaccination and possible arthritis flare among patients with rheumatoid arthritis in Hong Kong.

Ann Rheum Dis 2022 04 22;81(4):564-568. Epub 2021 Oct 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, China

Objectives: To investigate the relationship between COVID-19 full vaccination (two completed doses) and possible arthritis flare.

Methods: Patients with rheumatoid arthritis (RA) were identified from population-based electronic medical records with vaccination linkage and categorised into BNT162b2 (mRNA vaccine), CoronaVac (inactive virus vaccine) and non-vaccinated groups. The risk of possible arthritis flare after vaccination was compared using a propensity-weighted cohort study design. We defined possible arthritis flare as hospitalisation and outpatient consultation related to RA or reactive arthritis, based on diagnosis records during the episode. Weekly prescriptions of rheumatic drugs since the launch of COVID-19 vaccination programme were compared to complement the findings from a diagnosis-based analysis.

Results: Among 5493 patients with RA (BNT162b2: 653; CoronaVac: 671; non-vaccinated: 4169), propensity-scored weighted Poisson regression showed no significant association between arthritis flare and COVID-19 vaccination ((BNT162b2: adjusted incidence rate ratio 0.86, 95% Confidence Interval 0.73 to 1.01); CoronaVac: 0.87 (0.74 to 1.02)). The distribution of weekly rheumatic drug prescriptions showed no significant differences among the three groups since the launch of the mass vaccination programme (all p values >0.1 from Kruskal-Wallis test).

Conclusions: Current evidence does not support that full vaccination of mRNA or inactivated virus COVID-19 vaccines is associated with possible arthritis flare.
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http://dx.doi.org/10.1136/annrheumdis-2021-221571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550868PMC
April 2022

Two-dose COVID-19 vaccination and possible arthritis flare among patients with rheumatoid arthritis in Hong Kong.

Ann Rheum Dis 2022 04 22;81(4):564-568. Epub 2021 Oct 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, China

Objectives: To investigate the relationship between COVID-19 full vaccination (two completed doses) and possible arthritis flare.

Methods: Patients with rheumatoid arthritis (RA) were identified from population-based electronic medical records with vaccination linkage and categorised into BNT162b2 (mRNA vaccine), CoronaVac (inactive virus vaccine) and non-vaccinated groups. The risk of possible arthritis flare after vaccination was compared using a propensity-weighted cohort study design. We defined possible arthritis flare as hospitalisation and outpatient consultation related to RA or reactive arthritis, based on diagnosis records during the episode. Weekly prescriptions of rheumatic drugs since the launch of COVID-19 vaccination programme were compared to complement the findings from a diagnosis-based analysis.

Results: Among 5493 patients with RA (BNT162b2: 653; CoronaVac: 671; non-vaccinated: 4169), propensity-scored weighted Poisson regression showed no significant association between arthritis flare and COVID-19 vaccination ((BNT162b2: adjusted incidence rate ratio 0.86, 95% Confidence Interval 0.73 to 1.01); CoronaVac: 0.87 (0.74 to 1.02)). The distribution of weekly rheumatic drug prescriptions showed no significant differences among the three groups since the launch of the mass vaccination programme (all p values >0.1 from Kruskal-Wallis test).

Conclusions: Current evidence does not support that full vaccination of mRNA or inactivated virus COVID-19 vaccines is associated with possible arthritis flare.
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http://dx.doi.org/10.1136/annrheumdis-2021-221571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550868PMC
April 2022

Bell's palsy following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines: a case series and nested case-control study.

Lancet Infect Dis 2022 01 16;22(1):64-72. Epub 2021 Aug 16.

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 Special Administrative Region, China; Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Sha Tin, Hong Kong Special Administrative Region, China; Expert Committee on Clinical Events Assessment Following COVID-19 Immunization, Department of Health, The Government of the Hong Kong Special Administrative Region, Hong Kong Special Administrative Region, China; Research Department of Practice and Policy, School of Pharmacy, University College London, London, UK. Electronic address:

Background: Bell's palsy is a rare adverse event reported in clinical trials of COVID-19 vaccines. However, to our knowledge no population-based study has assessed the association between the inactivated SARS-CoV-2 vaccines and Bell's palsy. The aim of this study was to evaluate the risk of Bell's palsy after BNT162b2 and CoronaVac vaccination.

Methods: In this case series and nested case-control study done in Hong Kong, we assessed the risk of Bell's palsy within 42 days following vaccination with BNT162b2 (Fosun-BioNTech [equivalent to Pfizer-BioNTech]) or CoronaVac (from Sinovac Biotech, Hong Kong) using data from voluntary surveillance reporting with the Hospital Authority, the COVID-19 Vaccine Adverse Event Online Reporting system for all health-care professionals, and the Hospital Authority's territory-wide electronic health records from the Clinical Data Analysis and Reporting System. We described reported cases of Bell's palsy among vaccine recipients (aged 18-110 years for CoronaVac and aged 16-110 years for BNT162b2). We compared the estimated age-standardised incidence of clinically confirmed cases among individuals who had received the CoronaVac or BNT162b2 vaccination (up to 42 days before presentation) with the background incidence in the population. A nested case-control study was also done using conditional logistic regression to estimate the odds ratio (OR) for risk of Bell's palsy and vaccination. Cases and controls were matched (1:4) by age, sex, admission setting, and admission date.

Findings: Between February 23 and May 4, 2021, 451 939 individuals received the first dose of CoronaVac and 537 205 individuals received the first dose of BNT162b2. 28 clinically confirmed cases of Bell's palsy were reported following CoronaVac and 16 cases were reported following BNT162b2. The age-standardised incidence of clinically confirmed Bell's palsy was 66·9 cases per 100 000 person-years (95% CI 37·2 to 96·6) following CoronaVac vaccination and 42·8 per 100 000 person-years (19·4 to 66·1) for BNT162b2 vaccination. The age-standardised difference for the incidence compared with the background population was 41·5 (95% CI 11·7 to 71·4) for CoronaVac and 17·0 (-6·6 to 40·6) for BNT162b2, equivalent to an additional 4·8 cases per 100 000 people vaccinated for CoronaVac and 2·0 cases per 100 000 people vaccinated for BNT162b2. In the nested case-control analysis, 298 cases were matched to 1181 controls, and the adjusted ORs were 2·385 (95% CI 1·415 to 4·022) for CoronaVac and 1·755 (0·886 to 3·477) for BNT162b2.

Interpretation: Our findings suggest an overall increased risk of Bell's palsy after CoronaVac vaccination. However, the beneficial and protective effects of the inactivated COVID-19 vaccine far outweigh the risk of this generally self-limiting adverse event. Additional studies are needed in other regions to confirm our findings.

Funding: The Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, China.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1473-3099(21)00451-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367195PMC
January 2022

Age-Specific Associations of Usual Blood Pressure Variability With Cardiovascular Disease and Mortality: 10-Year Diabetes Mellitus Cohort Study.

J Am Heart Assoc 2021 09 16;10(17):e019026. Epub 2021 Aug 16.

Department of Family Medicine and Primary Care The University of Hong Kong Hong Kong SAR China.

Background The detrimental effects of increased variability in systolic blood pressure (SBP) on cardiovascular disease (CVD) and mortality risk in patients with diabetes mellitus remains unclear. This study evaluated age-specific association of usual SBP visit-to-visit variability with CVD and mortality in patients with type 2 diabetes mellitus. Methods and Results A retrospective cohort study investigated 155 982 patients with diabetes mellitus aged 45 to 84 years without CVD at baseline (2008-2010). Usual SBP variability was estimated using SBP SD obtained from a mixed-effects model. Age-specific associations (45-54, 55-64, 65-74, 75-84 years) between usual SBP variability, CVD, and mortality risk were assessed by Cox regression adjusted for patient characteristics. After a median follow-up of 9.7 years, 49 816 events (including 34 039 CVD events and 29 211 mortalities) were identified. Elevated SBP variability was independently, positively, and log-linearly associated with higher CVD and mortality risk among all age groups, with no evidence of any threshold effects. The excess CVD and mortality risk per 5 mm Hg increase in SBP variability within the 45 to 54 age group is >3 times higher than the 70 to 79 age group (hazard ratio, 1.66; 95% CI, 1.49-1.85 versus hazard ratio, 1.19; 95% CI, 1.15-1.23). The significant associations remained consistent among all subgroups. Patients with younger age had a higher association of SBP variability with event outcomes. Conclusions The findings suggest that SBP visit-to-visit variability was strongly associated with CVD and mortality with no evidence of a threshold effect in a population with diabetes mellitus. As well as controlling overall blood pressure levels, SBP visit-to-visit variability should be monitored and evaluated in routine practice, in particular for younger patients.
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http://dx.doi.org/10.1161/JAHA.120.019026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649287PMC
September 2021

Association between health behaviours and cardiometabolic dysregulation: a population-based survey among healthy adults in Hong Kong.

BMJ Open 2021 07 9;11(7):e043503. Epub 2021 Jul 9.

Department of Family Medicine and Primary Care, The University of Hong Kong, Hong Kong.

Objective: To explore the association between cardiometabolic dysregulation, an integral component of allostatic load, and health risk behaviours (HRBs) of the Hong Kong healthy adult population.

Design: Secondary analysis of cross-sectional anonymous data.

Setting: Data on sociodemographics, self-reported health status, HRBs and biomarkers were extracted from the Hong Kong Population Health Survey 2014/2015.

Participants: One thousand five hundred and fifty-one participants aged 18-64 years without self-reported diagnoses of hypertension, diabetes mellitus, hyperlipidaemia, cardiovascular disease, cognitive impairment or cancer.

Primary Outcome Measures: Cardiometabolic dysregulation index (CMDI), ranging from 0 to 6, was calculated by counting the number of biomarkers including systolic blood pressure, diastolic blood pressure, waist to hip ratio, glycated haemoglobin, total cholesterol to high-density lipoprotein cholesterol ratio, and triglycerides that were above the respective normal level suggested by international guidelines and literature. HRBs including smoking, dietary habits and sleeping hours were collected by self-report questionnaire. Alcohol consumption was assessed by the 10-item Alcohol Use Disorders Identification Test, while physical activity level was measured using the Global Physical Activity Questionnaire. A composite HRB score, ranging from 0 to 5, was calculated as the cumulative number of HRBs. The effect of HRB on CMDI was evaluated by negative binomial regression with adjustment for socioeconomic status, health awareness and comorbidities of the participants.

Results: The mean CMDI of the studied population was 1.6; 29.5% had a CMDI of 0, whereas 1.5% had a CMDI of 6. Significant difference was observed in mean CMDI between gender and different age groups. Sleeping less than 6 hours (incidence rate ratio (IRR)=1.26, p<0.001), smoking (IRR=1.15, p=0.027), insufficient physical activity (IRR=1.12, p=0.007) and higher composite HRB score (IRR=1.12, 95% CI 1.06 to 1.18) were significantly associated with higher CMDI.

Conclusion: Smoking, physical inactivity and inadequate sleep-an essential yet often overlooked health behaviour-were associated with higher CMDI in the Hong Kong healthy adult population.
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http://dx.doi.org/10.1136/bmjopen-2020-043503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273464PMC
July 2021

Effects of continuity of care on health outcomes among patients with diabetes mellitus and/or hypertension: a systematic review.

BMC Fam Pract 2021 07 3;22(1):145. Epub 2021 Jul 3.

Department of Family Medicine and Primary Care, The University of Hong Kong, 3/F Ap Lei Chau Clinic, 161 Main Street, Ap Lei Chau, Hong Kong, China.

Background: The rising prevalence of non-communicable diseases (NCDs) such as diabetes mellitus (DM) and hypertension (HT) has placed a tremendous burden on healthcare systems around the world, resulting in a call for more effective service delivery models. Better continuity of care (CoC) has been associated with improved health outcomes. This review examines the association between CoC and health outcomes in patients with DM and/or HT.

Methods: This was a systematic review with searches carried out on 13 March 2021 through PubMed, Embase, MEDLINE and CINAHL plus, clinical trials registry and bibliography reviews. Eligibility criteria were: published in English; from 2000 onwards; included adult DM and/or HT patients; examined CoC as their main intervention/exposure; and utilised quantifiable outcome measures (categorised into health indicators and service utilisation). The study quality was evaluated with Critical Appraisal Skills Programme (CASP) appraisal checklists.

Results: Initial searching yielded 21,090 results with 42 studies meeting the inclusion criteria. High CoC was associated with reduced hospitalisation (16 out of 18 studies), emergency room attendances (eight out of eight), mortality rate (six out of seven), disease-related complications (seven out of seven), and healthcare expenses (four out of four) but not with blood pressure (two out of 13), lipid profile (one out of six), body mass index (zero out of three). Six out of 12 studies on diabetic outcomes reported significant improvement in haemoglobin A1c by higher CoC. Variations in the classification of continuity of care and outcome definition were identified, making meta-analyses inappropriate. CASP evaluation rated most studies fair in quality, but found insufficient adjustment on confounders, selection bias and short follow-up period were common limitations of current literatures.

Conclusion: There is evidence of a strong association between higher continuity of care and reduced mortality rate, complication risks and health service utilisation among DM and/or HT patients but little to no improvement in various health indicators. Significant methodological heterogeneity in how CoC and patient outcomes are assessed limits the ability for meta-analysis of findings. Further studies comprising sufficient confounding adjustment and standardised definitions are needed to provide stronger evidence of the benefits of CoC on patients with DM and/or HT.
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http://dx.doi.org/10.1186/s12875-021-01493-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254900PMC
July 2021

Prognostic value of perfusion cardiovascular magnetic resonance with adenosine triphosphate stress in stable coronary artery disease.

J Cardiovasc Magn Reson 2021 06 24;23(1):75. Epub 2021 Jun 24.

Cardiology Division, Department of Medicine, The University of Hong Kong, Hong Kong, China.

Background: Adenosine triphosphate (ATP) has been predominantly used in the Asia-Pacific region for stress perfusion cardiovascular magnetic resonance (CMR). We evaluated the prognosis of patients stressed using ATP, for which there are no current data.

Methods: We performed a retrospective longitudinal study from January 2016 to December 2020 and included 208 subjects with suspected obstructive coronary artery disease (CAD) who underwent ATP stress perfusion CMR. An inducible stress perfusion defect was defined as a subendocardial dark rim involving ≥ 1.5 segments that persisted for ≥ 6 beats during stress but not at rest. The primary outcome measure was a composite of major adverse cardiovascular events (MACE) including (1) cardiac death, (2) nonfatal myocardial infarction, (3) cardiac hospitalization, (4) late coronary revascularization. We compared outcomes in patients with and without perfusion defect using Kaplan-Meier and log rank tests. Significant predictors of MACE were identified using multivariable Cox regression analysis.

Results: Median follow-up was 3.3 years. Patients with no stress perfusion defect had a lower incidence of MACE (p < 0.001), including lower cardiac hospitalization (p = 0.004), late coronary revascularization (p = 0.001) and cardiac death (p = 0.003). Significant independent predictors for MACE were stress induced perfusion defect (p < 0.001, hazard ratio [HR] = 3.63), lower left ventricular ejection fractino (LVEF) (p < 0.001, HR = 0.96) and infarct detected by late gadolinium enhancement (LGE) (p = 0.001, HR = 2.92).

Conclusion: Perfusion defects on ATP stress are predictive of MACE which is driven primarily by cardiac hospitalization, late coronary revascularization and cardiac death. Significant independent predictors of MACE were stress induced perfusion defect, lower LVEF and infarct detected by LGE.
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http://dx.doi.org/10.1186/s12968-021-00770-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223349PMC
June 2021

Comparative Risks of Nonsteroidal Anti-Inflammatory Drugs on CKD.

Clin J Am Soc Nephrol 2021 06 28;16(6):898-907. Epub 2021 Apr 28.

Department of Family Medicine and Primary Care, The University of Hong Kong, Hong Kong.

Background And Objectives: There have been doubts about the association between nonsteroidal anti-inflammatory drug use and worsening kidney function, and whether there is a difference between risks of individual nonsteroidal anti-inflammatory drugs is presently unclear. Therefore, this study aimed to evaluate the association between nonsteroidal anti-inflammatory drug exposure and the risk of incident eGFR <60 ml/min per 1.73 m and compare the risks between nonsteroidal anti-inflammatory drug subtypes in the Chinese population.

Design, Setting, Participants, & Measurements: From 2008 to 2017, a total of 1,982,488 subjects aged 18 years or older with baseline eGFR ≥60 ml/min per 1.73 m were enrolled in this retrospective cohort study. Multivariable Cox proportional hazards regression adjusted for each patient's baseline characteristics was adopted to examine the association between nonsteroidal anti-inflammatory drug and incident eGFR <60 ml/min per 1.73 m or eGFR decline ≥30% with reference to baseline.

Results: After a median follow-up duration of 6.3 (interquartile range, 3.3-9.4) years, 271,848 cases (14%) of incident eGFR <60 ml/min per 1.73 m and 388,386 (21%) events of eGFR decline ≥30% were recorded. After adjusting for each patient's baseline characteristics, nonsteroidal anti-inflammatory drug treatment was shown to be associated with a significantly higher risk of incident eGFR <60 ml/min per 1.73 m (hazard ratio, 1.71; 95% confidence interval, 1.67 to 1.75) and eGFR decline ≥30% (hazard ratio, 1.93; 95% confidence interval, 1.89 to 1.96) when compared with no nonsteroidal anti-inflammatory drug, with etoricoxib exhibiting the highest risk of eGFR<60 ml/min per 1.73 m (hazard ratio, 3.12; 95% confidence interval, 2.69 to 3.62) and eGFR decline ≥30% (hazard ratio, 3.11; 95% confidence interval, 2.78 to 3.48) and ibuprofen displaying the lowest risk of eGFR<60 ml/min per 1.73 m (hazard ratio, 1.12; 95% confidence interval, 1.02 to 1.23) and eGFR decline ≥30% (hazard ratio, 1.32; 95% confidence interval, 1.23 to 1.41).

Conclusions: Nonsteroidal anti-inflammatory drug exposure was associated with higher risks of incident eGFR <60 ml/min per 1.73 m and eGFR decline ≥30%. Highest risk was observed in etoricoxib users, and lowest risk was with ibuprofen.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_04_28_CJN18501120.mp3.
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http://dx.doi.org/10.2215/CJN.18501120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216605PMC
June 2021

Generative adversarial networks for imputing missing data for big data clinical research.

BMC Med Res Methodol 2021 04 20;21(1):78. Epub 2021 Apr 20.

Department of Family Medicine and Primary Care, Faculty of Medicine, University of Hong Kong, Hong Kong, Hong Kong SAR, China.

Background: Missing data is a pervasive problem in clinical research. Generative adversarial imputation nets (GAIN), a novel machine learning data imputation approach, has the potential to substitute missing data accurately and efficiently but has not yet been evaluated in empirical big clinical datasets.

Objectives: This study aimed to evaluate the accuracy of GAIN in imputing missing values in large real-world clinical datasets with mixed-type variables. The computation efficiency of GAIN was also evaluated. The performance of GAIN was compared with other commonly used methods, MICE and missForest.

Methods: Two real world clinical datasets were used. The first was that of a cohort study on the long-term outcomes of patients with diabetes (50,000 complete cases), and the second was of a cohort study on the effectiveness of a risk assessment and management programme for patients with hypertension (10,000 complete cases). Missing data (missing at random) to independent variables were simulated at different missingness rates (20, 50%). The normalized root mean square error (NRMSE) between imputed values and real values for continuous variables and the proportion of falsely classified (PFC) for categorical variables were used to measure imputation accuracy. Computation time per imputation for each method was recorded. The differences in accuracy of different imputation methods were compared using ANOVA or non-parametric test.

Results: Both missForest and GAIN were more accurate than MICE. GAIN showed similar accuracy as missForest when the simulated missingness rate was 20%, but was more accurate when the simulated missingness rate was 50%. GAIN was the most accurate for the imputation of skewed continuous and imbalanced categorical variables at both missingness rates. GAIN had a much higher computation speed (32 min on PC) comparing to that of missForest (1300 min) when the sample size is 50,000.

Conclusion: GAIN showed better accuracy as an imputation method for missing data in large real-world clinical datasets compared to MICE and missForest, and was more resistant to high missingness rate (50%). The high computation speed is an added advantage of GAIN in big clinical data research. It holds potential as an accurate and efficient method for missing data imputation in future big data clinical research.

Trial Registration: ClinicalTrials.gov ID: NCT03299010 ; Unique Protocol ID: HKUCTR-2232.
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http://dx.doi.org/10.1186/s12874-021-01272-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059005PMC
April 2021

Greater variability in lipid measurements associated with kidney diseases in patients with type 2 diabetes mellitus in a 10-year diabetes cohort study.

Sci Rep 2021 04 13;11(1):8047. Epub 2021 Apr 13.

Department of Family Medicine and Primary Care, The University of Hong Kong, 3/F Ap Lei Chau Clinic, 161 Main Street, Ap Lei Chau, Hong Kong.

This study aimed to evaluate the associations between variability of lipid parameters and the risk of kidney disease in patients with type 2 diabetes mellitus. Low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were specifically addressed in this study. This retrospective cohort study included 105,552 patients aged 45-84 with type 2 diabetes mellitus and normal kidney function who were managed under Hong Kong public primary care clinics during 2008-2012. Those with kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m or urine albumin to creatinine ratio ≥ 3 mg/mmol) were excluded. Variabilities of low-density lipoprotein-cholesterol, total cholesterol to high-density lipoprotein-cholesterol ratio and triglyceride were determined using the standard deviation of the respective parameter obtained from a mixed effects model to minimize regression dilution bias. The associations between lipid variability and renal outcomes including incident kidney disease, renal function decline defined as ≥ 30% reduction in estimated glomerular filtration rate since baseline, and end-stage renal disease (estimated glomerular filtration rate < 15 mL/min/1.73 m) were evaluated by multivariable Cox regression. After a median follow-up of 66.5 months (0.5 million person-years in total), 49,653 kidney disease, 29,358 renal function decline, and 1765 end-stage renal disease cases were recorded. Positive linear associations between low-density lipoprotein-cholesterol and total cholesterol to high-density lipoprotein-cholesterol ratio variabilities and the risk of all renal outcomes were demonstrated. However, no association between triglyceride variability and any outcome was found. Each mmol/L increase in low-density lipoprotein-cholesterol variability was associated with 20% (Hazard ratio 1.20 [95% CI 1.15-1.25]), 38% (Hazard ratio 1.37 [95% CI 1.30-1.45]), and 108% (Hazard ratio 2.08 [95% CI 1.74-2.50]) higher risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Similarly, each unit increase in total cholesterol to high-density lipoprotein-cholesterol ratio variability was associated with 35% (Hazard ratio 1.15 [95% CI 1.10-1.20]), 33% (Hazard ratio 1.33 [95% CI 1.26-1.40]), and 75% (Hazard ratio 1.75 [95% CI 1.46-2.09]) heightened risk in incident kidney disease, renal function decline and end-stage renal disease respectively. Cholesterol variability may potentially be a useful predictor of kidney diseases in patients with type 2 diabetes mellitus. Attention should be drawn to cholesterol variability when managing diabetic patients and further research is warranted to investigate the modifiable risk factors for lipid variability.
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http://dx.doi.org/10.1038/s41598-021-87067-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044222PMC
April 2021

COVID-19 and Health-Related Quality of Life: A Community-Based Online Survey in Hong Kong.

Int J Environ Res Public Health 2021 03 20;18(6). Epub 2021 Mar 20.

School of Nursing, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

The COVID-19 pandemic itself and related public health measurements have had substantial impacts on individual social lives and psychological and mental health, all to the detriment of health-related quality of life (HRQoL). There have been extensive studies investigating the mental health of people in different populations during the COVID-19 pandemic. However, few studies have explored the impact of COVID-19 and its association with HRQoL. To fill this research gap and provide further empirical evidence, this study examined the impact of COVID-19 on Hong Kong people and evaluated its association with HRQoL. A total of 500 participants were randomly recruited to complete an online questionnaire on their concerns related to COVID-19. This entailed responding to the World Health Organization Quality of Life-BREF instrument. Data were collected between 24 April and 3 May 2020. Independent t-tests and multiple linear regressions were used to examine the association between the impact of COVID-19 and HRQoL. Overall, 69.6% of participants were worried about contracting COVID-19, and 41.4% frequently suspected themselves of being infected. Furthermore, 29.0% were concerned by the lack of disinfectants. All of these findings were associated with poorer HRQoL in the physical and psychological health, social relationships, and environment domains. On the other hand, 47.4% of participants were concerned that they may lose their job because of the pandemic, while 39.4% were bothered by the insufficient supply of surgical masks. These two factors were associated with poorer HRQoL in the physical and psychological health and environment domains. The adverse impact of COVID-19 on individuals is multifactorial, affecting all aspects of HRQoL. In addition to enhancing anti-epidemic efforts, it is equally important to implement public health and social welfare measures, thereby diminishing the adverse impact of COVID-19 on overall well-being.
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http://dx.doi.org/10.3390/ijerph18063228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003940PMC
March 2021

Retrospective cohort study to investigate the 10-year trajectories of disease patterns in patients with hypertension and/or diabetes mellitus on subsequent cardiovascular outcomes and health service utilisation: a study protocol.

BMJ Open 2021 02 5;11(2):e038775. Epub 2021 Feb 5.

Department of Family Medicine and Primary Care, The University of Hong Kong, Hong Kong SAR, China.

Introduction: Hypertension (HT) and diabetes mellitus (DM) and are major disease burdens in all healthcare systems. Given their high impact on morbidity, premature death and direct medical costs, we need to optimise effectiveness and cost-effectiveness of primary care for patients with HT/DM. This study aims to find out the association of trajectories in disease patterns and treatment of patients with HT/DM including multimorbidity and continuity of care with disease outcomes and service utilisation over 10 years in order to identify better approaches to delivering primary care services.

Methods And Analysis: A 10-year retrospective cohort study on a population-based primary care cohort of Chinese patients with documented doctor-diagnosed HT and/or DM, managed in the Hong Kong Hospital Authority (HA) public primary care clinics from 1 January 2006 to 31 December 2019. Data will be extracted from the HA Clinical Management System to identify trajectory patterns of patients with HT/DM. Complications defined by ICPC-2/International Classification of Diseases-Ninth Revision, Clinical Modification diagnosis codes, all-cause mortality rates and public service utilisation rates are included as independent variables. Changes in clinical parameters will be investigated using a growth mixture modelling analysis with standard quadratic trajectories. Dependent variables including effects of multimorbidity, measured by (1) disease count and (2) Charlson's Comorbidity Index, and continuity of care, measured by the Usual Provide Continuity Index, on patient outcomes and health service utilisation will be investigated. Multivariable Cox proportional hazards regression will be conducted to estimate the effect of multimorbidity and continuity of care after stratification of patients into groups according to respective definitions.

Ethics And Dissemination: This study was approved by the institutional review board of the University of Hong Kong-the HA Hong Kong West Cluster, reference no: UW 19-329. The study findings will be disseminated through peer-reviewed publications and international conferences.

Trial Registration Number: NCT04302974.
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http://dx.doi.org/10.1136/bmjopen-2020-038775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925871PMC
February 2021

Health-related quality of life among Chinese primary care patients with different lower urinary tract symptoms: a latent class analysis.

Qual Life Res 2021 May 14;30(5):1305-1315. Epub 2021 Jan 14.

Department of Family Medicine and Primary Care, University of Hong Kong, Pokfulam, Hong Kong.

Purpose: No previous study has used a data-driven approach to explore symptom subclasses among patients with lower urinary tract symptoms (LUTS). The objectives of this study were to use latent class analysis (LCA) to identify distinct classes of LUTS among primary care patients and to assess the class differences in health-related quality of life (HRQOL).

Methods: In this cross-sectional study, 500 patients were randomly recruited, and 18 symptoms according to the International Continence Society 2002 criteria were assessed. Classes were identified by LCA. Patient HRQOL was measured using the 12-item Short Form Health Survey (version 2), the modified Incontinence Impact Questionnaire-Short Form and the HRQOL item from the International Prostate Symptom Score.

Results: Six distinct LUTS classes were identified: "asymptomatic" (26.0%), "mild symptoms" (22.6%), "moderate multiple symptoms" (17.0%), "urgency symptoms" (13.8%), "urinary incontinence" (12.0%) and "severe multiple symptoms" (8.6%). Multinomial regression analysis found differences in the gender distribution and prevalence of heart diseases across classes, and multiple linear regression found that patients with "severe multiple symptoms" and "urinary incontinence" had the poorest HRQOL.

Conclusion: Almost three quarters of the primary care patients in this study were suffering from varying degrees of LUTS. The poor HRQOL in "severe multiple symptoms" and "urinary incontinence" implies that patients in these classes require additional attention and treatments.
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http://dx.doi.org/10.1007/s11136-020-02731-yDOI Listing
May 2021
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