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Abstract Several international pharmacovigilance agencies have issued warnings regarding the potential risk of myasthenia gravis (MG) following statin therapy. Our study investigated this association using population-based electronic health records in Hong Kong. We conducted a sequence of target trial emulation (TTE) for interpersonal comparison and a self-controlled case series (SCCS) study for intrapersonal comparison. In the TTE for MG onset, the incidence rates (per 100,000 person-years) and adjusted HRs were 51.91(31.80, 84.74)[HR:6.11 (3.73, 10.01)] in month 1, 16.27(9.81, 26.99)[HR:1.92(1.15, 3.19) in months 2-4, and 15.27(9.05, 25.79)[HR:1.80(1.06, 3.04)] in months 5–7. For risk of exacerbation, the adjusted HRs were 10.69(5.48, 20.84) in month 1, 1.50(0.55, 4.06) in months 2–4, and 2.79(1.33, 5.84) in months 5–7. No increased risks were found during the subsequent 18 months. A similar pattern was observed in SCCS analysis. Our findings recommend a minimum monitoring period of approximately six months for MG symptoms for patients starting using statin.

Abstract Background Few studies have attempted to use clinical and laboratory parameters to stratify COVID-19 patients with severe versus non-severe initial disease and evaluate age-specific differences in developing multiple different COVID-19-associated disease outcomes. Methods A retrospective cohort included patients from the electronic health database of Hong Kong Hospital Authority between 1 January 2022 and 15 August 2022 until 15 November 2022. The cohort was divided into three cohorts by age (≤ 40, 41–64, and ≥ 65 years old). Each age cohort was stratified into four groups: (1) COVID-19 critically exposed group (ICU admission, mechanical ventilation support, CRP > 80 mg/L, or D-dimer > 2 g/mL), (2) severely exposed group (CRP 30–80 mg/L, D-dimer 0.5–2 g/mL, or CT value 40) for the disease outcomes in the acute phase of infection (e.g., mortality risk HR (aged ≤ 40): 1.0 (95%CI: 0.5,2.0), HR (aged 41–64): 2.1 (95%CI: 1.8, 2.6), HR (aged > 65): 4.8 (95%CI: 4.6, 5.1)); while in the post-acute phase, these risks were largely insignificant in those aged 65): 1.5 (95%CI: 1.5,1.6)). Fully vaccinated patients were associated with lower risks of disease outcomes than those receiving less than two doses of vaccination. Conclusions The risk of multiple different disease outcomes in both acute and post-acute phases increased significantly with the increasing severity of acute COVID-19 illness, specifically among the elderly. Moreover, future studies could improve by risk-stratifying patients based on universally accepted thresholds for clinical parameters, particularly biomarkers, using biological evidence from immunological studies.

Abstract Background Extending the dosing interval of a primary series of mRNA COVID-19 vaccination has been employed to reduce myocarditis risk in adolescents, but previous evaluation of impact on vaccine effectiveness (VE) is limited to risk after second dose. Methods We quantified the impact of the dosing interval based on case notifications and vaccination uptake in Hong Kong from January to April 2022, based on calendar-time proportional hazards models and matching approaches. Results We estimated that the hazard ratio (HR) and odds ratio (OR) of infections after the second dose for extended (28 days or more) versus regular (21–27 days) dosing intervals ranged from 0.86 to 0.99 from calendar-time proportional hazards models, and from 0.85 to 0.87 from matching approaches, respectively. Adolescents in the extended dosing groups (including those who did not receive a second dose in the study period) had a higher hazard of infection than those with a regular dosing interval during the intra-dose period (HR 1.66; 95% CI 1.07, 2.59; p = 0.02) after the first dose. Conclusions Implementing an extended dosing interval should consider multiple factors including the degree of myocarditis risk, the degree of protection afforded by each dose, and the extra protection achievable using an extended dosing interval.

Abstract Background Limited research exists on the risks and spectrum of complications in post‐acute phase of COVID‐19 in cancer patients. This study aimed to evaluate the post‐acute effects of COVID‐19 on different types of morbidities among cancer patients across two regions with different healthcare systems and dominant variants of COVID‐19. Materials and Methods Cancer patients with COVID‐19 from the UK Biobank (UKB, n = 2230; March 16, 2020 to May 31, 2021; pre‐Omicron‐variants dominant) and electronic medical records in Hong Kong (HK cohort, n = 22,335; April 1, 2020 to October 31, 2022; Omicron‐variant dominant) were included. Each COVID‐19 case was randomly matched with up to 10 non‐COVID‐19 cancer patients based on age and sex. Follow‐up lasted until 31 August 2021 for UKB and 23 January 2023 for HK. Inverse probability treatment weighting balanced cohort characteristics. Cox regression evaluated the association of COVID‐19 with morbidities occurred 30 days post‐infection. Results Cancer patients with COVID‐19 consistently showed significantly higher risk of major cardiovascular diseases (CVDs) [UKB: hazard ratio [HR] 1.8 (95% CI 1.3, 2.5); HK: HR 1.4 (95% CI 1.1, 1.8)], CVD death [UKB: HR 4.3 (95% CI 2.9, 6.2); HK: HR 1.7 (95% CI 1.3, 2.4)], and all‐cause mortality [UKB: HR 4.7 (95% CI 4.0, 5.5); HK: HR 1.6 (95% CI 1.5, 1.7)] in both cohorts despite the difference in dominant variants. Cancer patients at advanced ages or severely infected had higher all‐cause mortality risk. However, associations between COVID‐19 and CVDs became insignificant for fully vaccinated patients. Conclusion COVID‐19 infection is associated with increased risks of CVDs and mortality in cancer patients. Fully vaccination may reduce the post‐acute effects of COVID‐19 on CVDs. This information may guide effective pre‐emptive measures to reduce COVID‐19‐related morbidities and mortality in cancer patients.

BackgroundClozapine is widely regarded as a highly efficacious psychotropic drug that is largely underused worldwide. Recent disproportionality analyses and nationwide case-control studies suggested a potential association between clozapine use and hematological malignancy (HM). Nevertheless, the absolute rate difference is not well-established due to the absence of analytic cohort studies. The clinical significance of such a potential risk remains unclear.Methods and findingsWe extracted data from a territory-wide public healthcare database from January 2001 to August 2022 in Hong Kong to conduct a retrospective cohort study of anonymized patients aged 18+ years with a diagnosis of schizophrenia who used clozapine or olanzapine (drug comparator with highly similar chemical structure and pharmacological mechanisms) for 90+ days, with at least 2 prior other antipsychotic use records within both groups. Weighted by inverse probability of treatment (IPTW) based on propensity scores, Poisson regression was used to estimate the incidence rate ratio (IRR) of HM between clozapine and olanzapine users. The absolute rate difference was also estimated. In total, 9,965 patients with a median follow-up period of 6.99 years (25th to 75th percentile: 4.45 to 10.32 years) were included, among which 834 were clozapine users. After IPTW, the demographic and clinical characteristics of clozapine users were comparable to those of olanzapine users. Clozapine users had a significant weighted IRR of 2.22 (95% confidence interval (CI) [1.52, 3.34]; p < 0.001) for HM compared to olanzapine users. The absolute rate difference was estimated at 57.40 (95% CI [33.24, 81.55]) per 100,000 person-years. Findings were consistent across subgroups by age and sex. Sensitivity analyses all supported the robustness of the results and showed good specificity to HM but no other cancers. The main limitation of this observational study is the potential residual confounding effects that could have arisen from the lack of randomization in clozapine or olanzapine use.ConclusionsAbsolute rate difference in HM incidence associated with clozapine is small despite a 2-fold elevated rate. Given the rarity of HM and existing blood monitoring requirements, more restrictive indication for clozapine or special warnings may not be necessary.

Background: Approximately two-thirds of diabetes patients develop multimorbidity, which is associated with increased mortality. We aimed to examine whether, and to what extent, the time interval between pre-existing diabetes and a second chronic disease may be associated with the risk of mortality. Methods: We carried out a territory-wide nested case-control study using incidence density sampling, utilizing electronic health records from Hong Kong’s public healthcare facilities. Among 158 732 patients first diagnosed with diabetes from January 1, 2010 to December 31, 2012 and subsequently developed multimorbidity as of December 31, 2019, we extracted those who died before December 31, 2019 as case participants. For each participant, we randomly matched with up to 4 people of the same sex, multimorbidity age, and second chronic condition who had not died after going through the same survival period of the case participant. Multimorbidity interval was included as a continuous variable. We used conditional logistic regression to estimate adjusted odds ratios (aOR) for mortality. Results: In total, 3508 case participants were matched with 14 032 control participants. Conditional logistic regression showed there were 19%-reduced odds of mortality following the extension of multimorbidity interval by 1 year. Similar associations were observed in men, women, people aged 64 years or younger, and older people aged 65 years or more. Conclusions: Delayed multimorbidity among patients living with diabetes may be related to a lower risk of mortality. This study suggests that we should focus on mitigating and lowering the risk of multimorbidity in clinical management of diabetes to reduce further complication and mortality.

Abstract Objective To evaluate age-specific multimorbidity patterns and morbidity burden on mortality and healthcare expenditure across age groups. Patients and Methods Retrospective observational study between January 1, 2009 to December 31, 2017 using electronic health records in Hong Kong: Individuals were stratified by age (

Objectives: To evaluate the difference between BNT162b2 and CoronaVac in vaccine effectiveness and safety. Methods: This target trial emulation study included individuals aged ≥12 during 2022. Propensity score matching was applied to ensure group balance. The Cox proportional hazard model was used to compare the effectiveness outcomes including COVID-19 infection, severity, 28-day hospitalization, and 28-day mortality after infection. Poisson regression was used for safety outcomes including 32 adverse events of special interests between groups. Results: A total of 639,818 and 1804,388 individuals were identified for the 2-dose and 3-dose comparison, respectively. In 2-dose and 3-dose comparison, the hazard ratios (95% confidence intervals [CI]) were 0.844 [0.833-0.856] and 0.749 [0.743-0.755] for COVID-19 infection, 0.692 [0.656-0.731] and 0.582 [0.559-0.605] for hospitalization, 0.566 [0.417-0.769] and 0.590 [0.458-0.76] for severe COVID-19, and 0.563 [0.456-0.697] and 0.457 [0.372-0.561] for mortality for BNT162b2 recipients versus CoronaVac recipients, respectively. Regarding safety, 2-dose BNT162b2 recipients had a significantly higher incidence of myocarditis (incidence rate ratio [IRR] [95% CI]: 8.999 [1.14-71.017]) versus CoronaVac recipients, but the difference was insignificant in 3-dose comparison (IRR [95% CI]: 2.000 [0.500-7.996]). Conclusion: BNT162b2 has higher effectiveness among individuals aged ≥12 against COVID-19-related outcomes for SARS-CoV-2 omicron compared to CoronaVac, with almost 50% lower mortality risk.

Objectives Older individuals with multimorbidity are at an elevated risk of infection and complications from COVID-19. Effectiveness of post-COVID-19 interventions or care models in reducing subsequent adverse outcomes in these individuals have rarely been examined. This study aims to examine the effectiveness of attending general outpatient within 30 days after discharge from COVID-19 on 1-year survival among older adults aged 85 years or above with multimorbidity.Design Retrospective cohort study emulating a randomised target trial using electronic health records.Setting We used data from the Hospital Authority and the Department of Health in Hong Kong, which provided comprehensive electronic health records, COVID-19 confirmed case data, population-based vaccination records and other individual characteristics for the study.Participants Adults aged 85 years or above with multimorbidity who were discharged after hospitalisation for COVID-19 between January 2020 and August 2022.Interventions Attending a general outpatient within 30 days of last COVID-19 discharge defined the exposure, compared to no outpatient visit.Main outcome measures Primary outcome was all-cause mortality within one year. Secondary outcomes included mortality from respiratory, cardiovascular and cancer causes.Results A total of 6183 eligible COVID-19 survivors were included in the analysis. The all-cause mortality rate following COVID-19 hospitalisation was lower in the general outpatient visit group (17.1 deaths per 100 person-year) compared with non-visit group (42.8 deaths per 100 person-year). After adjustment, primary care consultations within 30 days after discharge were associated with a significantly greater 1-year survival (difference in 1-year survival: 11.2%, 95% CI 8.1% to 14.4%). We also observed significantly better survival from respiratory diseases in the general outpatient visit group (difference in 1-year survival: 6.3%, 95% CI 3.5% to 8.9%). In a sensitivity analysis for different grace period lengths, we found that the earlier participants had a general outpatient visit after COVID-19 discharge, the better the survival.Conclusions Timely primary care consultations after COVID-19 hospitalisation may improve survival following COVID-19 hospitalisation among older adults aged 85 or above with multimorbidity. Expanding primary care services and implementing follow-up mechanisms are crucial to support this vulnerable population’s recovery and well-being.

Abstract Previous studies indicate an increased carditis risk among adolescents following the two-dose messenger RNA COVID-19 vaccine. Several jurisdictions have extended the interdose interval between the first and second doses to reduce the risk. However, the effectiveness of such an extension policy remains inconclusive. Using the territory-wide vaccine record-linked electronic health records in Hong Kong, we conducted a nested case–control study from February 23, 2021 to August 15, 2022. Adolescents aged between 12 and 17 who received two-dose BNT162b2 were included for comparing risks between standard interdose interval (21–27 days) versus extended interdose interval ( ≥ 56 days). The carditis cumulative incidence within 28 days following the second dose was calculated. The adjusted odds ratio was estimated from multivariable conditional logistic regression. We identified 49 adolescents with newly diagnosed carditis within 28 days following the second dose. The crude cumulative incidence is 37.41 [95% confidence interval (CI): 27.68–49.46] per million vaccinated adolescents. Compared to the standard interdose interval group, adolescents with an extended interval had a significantly lower risk of carditis [adjusted odds ratio (aOR) 0.34 (95% CI: 0.16–0.73)]. Sensitivity analysis of carditis occurring within 14 days following the second dose yielded a similar estimate [aOR 0.30 (95% CI: 0.13–0.73)]. Extending the interdose interval of the BNT162b2 vaccine from 21 to 27 days to 56 days or longer is associated with 66% lower risk of incident carditis among adolescents. Our findings contribute towards an evidence-based vaccination strategy for a vulnerable population and potentially informs product label updates.

Abstract The persisting risk of long-term health consequences of SARS-CoV-2 infection and the protection against such risk conferred by COVID-19 vaccination remains unclear. Here we conducted a retrospective territory-wide cohort study on 1,175,277 patients with SARS-CoV-2 infection stratified by their vaccination status and non-infected controls to evaluate the risk of clinical sequelae, cardiovascular and all-cause mortality using a territory-wide public healthcare database with population-based vaccination records in Hong Kong. A progressive reduction in risk of all-cause mortality was observed over one year between patients with SARS-CoV-2 infection and controls. Patients with complete vaccination or have received booster dose incurred a lower risk of health consequences including major cardiovascular diseases, and all-cause mortality than unvaccinated or patients with incomplete vaccination 30-90 days after infection. Completely vaccinated and patients with booster dose of vaccines did not incur significant higher risk of health consequences from 271 and 91 days of infection onwards, respectively, whilst un-vaccinated and incompletely vaccinated patients continued to incur a greater risk of clinical sequelae for up to a year following SARS-CoV-2 infection. This study provided real-world evidence supporting the effectiveness of COVID-19 vaccines in reducing the risk of long-term health consequences of SARS-CoV-2 infection and its persistence following infection.

Summary: Multimorbidity entails a higher risk of SARS-CoV-2 infection and COVID-19 complications. We examined vaccine effectiveness (VE) stratified by multimorbidity using a case-control study of territory-wide electronic health records in Hong Kong. Cases of infection (testing positive), hospitalization, and mortality were identified from January to March 2022. Controls were matched by age, sex, outpatient attendance/hospitalization date, and Charlson Comorbidity Index. We demonstrated a consistently good VE among people with increased multimorbidity burden; even more so than among those with minimal such burden. There was also a significantly greater VE after a third dose of BNT162b2 or CoronaVac against infection. The difference in VE between those with multimorbidity and those without was less pronounced for hospitalization, and such difference for COVID-19-related mortality was negligible. In conclusion, VE of both examined vaccines against SARS-CoV-2 infection among people with more complex multimorbidity burden is significant. Further vaccine roll-out should prioritize people with multimorbidity.