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Purpose: The evidence of the neuropsychiatric effects associated with fluoroquinolones is mainly supported by case reports. Population‐based evidence remains largely limited. We aimed to investigate the association between the use of fluoroquinolones and hospitalization or Accident & Emergency department visits for acute neuropsychiatric events using a self‐controlled case series (SCCS) and active comparator to reduce confounding. Methods: We conducted a SCCS with a recently described active comparator design using all public outpatient clinics, hospitalization, and Accident and Emergency department records from the Clinical Data Analysis and Reporting System, Hong Kong from 2001 to 2013. Among 166 325 people with an oral fluoroquinolone prescription, 4287 people who had an incident neuropsychiatric event were included. We then estimated the incidence rate ratio (IRR) of acute neuropsychiatric events during periods before and after fluoroquinolone prescription, versus baseline. We repeated the analysis for amoxicillin/clavulanic acid users as an active comparator. We then estimated the comparator‐adjusted estimates by dividing the IRR for fluoroquinolone by the IRR for amoxicillin/clavulanic acid. The primary outcome was neuropsychiatric events. Secondary outcomes were psychotic events and cognitive impairment. Results: An increased risk of neuropsychiatric events was observed in the current use of fluoroquinolone [IRR: 2.11 (95% confidence interval (CI): 1.58–2.83)] and 1–7 days after the end of fluoroquinolone prescription [IRR: 1.90 (95% CI: 1.30–2.75)] versus baseline. No increased risk was observed in other risk periods versus baseline. Similar patterns were observed in the current use of amoxicillin/clavulanic acid [IRR: 1.92 (95% CI: 1.19–3.11)] and 1–7 days after the end of fluoroquinolone prescription [IRR: 1.81 (95% CI: 1.11–2.97)] versus baseline. Similar results were found for secondary outcomes. Using the active comparator design, comparator‐adjusted estimates were 1.10 (95% CI: 0.63–1.93) in current use of fluoroquinolones and 1.05 (95% CI: 0.57–1.95) in 1–7 days postexposure to fluoroquinolones versus baseline. Conclusions: Although our study showed a higher incidence of neuropsychiatric events in the current use of fluoroquinolones and 7 days after the end of fluoroquinolones prescriptions compared with baseline, a similar temporal pattern was also found for amoxicillin/clavulanic acid users. Using amoxicillin/clavulanic acid as the active comparator, we found no difference in the risk of neuropsychiatric events associated with fluoroquinolone compared with baseline. Therefore, the risk of neuropsychiatric events may not need to influence the decision to prescribe either fluoroquinolones or amoxicillin/clavulanic acid based on the evidence in this study. [ABSTRACT FROM AUTHOR]

Aims: To compare the effectiveness of molnupiravir and nirmatrelvir‐ritonavir for non‐hospitalized and hospitalized COVID‐19 patients with type 2 diabetes (T2DM). Materials and Methods: Territory‐wide electronic health records in Hong Kong were used to perform target trial emulation using a sequential trial approach. Patients (1) aged ≥18 years, (2) with T2DM, (3) with COVID‐19 infection, and (4) who received molnupiravir or nirmatrelvir‐ritonavir within 5 days of infection between 16 March 2022 and 31 December 2022 in non‐hospital and hospital settings were included. Molnupiravir and nirmatrelvir‐ritonavir initiators were matched using one‐to‐one propensity‐score matching and followed for 28 days. Risk of outcomes was compared between groups by Cox regression adjusted for baseline characteristics. Subgroup analyses were performed on age (<70 years, ≥70 years), sex, Charlson comorbidity index (<4, ≥4), and number of COVID‐19 vaccine doses (<2 doses, ≥2 doses). Results: Totals of 17 974 non‐hospitalized (8987 in each group) and 3678 hospitalized (1839 in each group) patients were identified. Non‐hospitalized nirmatrelvir‐ritonavir initiators had lower risk of all‐cause mortality (absolute risk reduction [ARR] at 28 days 0.80%, 95% confidence interval [CI] 0.56–1.04; hazard ratio [HR] 0.47, 95% CI 0.30–0.73) and hospitalization (ARR at 28 days 4.01%, 95% CI 3.19–4.83; HR 0.73, 95% CI 0.66–0.82) as compared with molnupiravir initiators. Hospitalized nirmatrelvir‐ritonavir initiators had reduced risk of all‐cause mortality (ARR at 28 days 2.94%, 95% CI 1.65–4.23; HR 0.56, 95% CI 0.40–0.80) as compared with molnupiravir initiators. Consistent findings were found across all subgroups. Conclusions: The use of nirmatrelvir‐ritonavir may be preferred to molnupiravir for COVID‐19 patients with T2DM and without contraindication to either treatment. [ABSTRACT FROM AUTHOR]

Population-based epidemiological studies on post-acute phase coronavirus 2019 (COVID-19)-related fractures in older adults are lacking. This study aims to examine the risk of incident major osteoporotic fractures following SARS-CoV-2 infection among individuals aged ≥50, compared to individuals without COVID-19. It was a retrospective, propensity-score matched, population-based cohort study of COVID-19 patients and non-COVID individuals identified from the electronic database of the Hong Kong Hospital Authority from January 2020 to March 2022. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, and upper limb). COVID-19 patients were 1:1 matched to controls using propensity-score according to age, sex, vaccination status, medical comorbidities and baseline medications. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 429 459 COVID-19 patients were included, 1:1 matched to non-COVID individuals. Upon median follow-up of 11 months, COVID-19 patients had higher risks of major osteoporotic fractures (5.08 vs 3.95 per 1000 persons; HR 1.22 95%CI [1.15–1.31]), hip fractures (2.71 vs 1.94; 1.33 [1.22–1.46]), clinical vertebral fractures (0.42 vs 0.31; 1.29 [1.03–1.62]), and falls (13.83 vs 10.36; 1.28 [1.23–1.33]). Subgroup analyses revealed no significant interaction. In acute (within 30 days) and post-acute phases (beyond 30 days) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we consistently observed a significant increase in fractures and falls risks. Our study demonstrated increased risk of major osteoporotic fractures after SARS-CoV-2 infection in both acute and post-acute phases in older adults, partly due to increased fall risk. Clinicians should be aware of musculoskeletal health of COVID-19 survivors. [ABSTRACT FROM AUTHOR]

Background: Previous studies investigating potential cardiovascular adverse events of acid-suppressing drugs are susceptible to protopathic bias and confounding. We aimed to investigate the association between short-term risk of myocardial infarction (MI) and proton pump inhibitors (PPIs) using a self-controlled case series (SCCS) with an active comparator.Methods: We conducted a SCCS using a population-wide database from Hong Kong from 2003-2014. Adult with ≥1 outpatient oral PPI prescription or H2 receptor antagonist (H2RA) and MI during the observation period were included. We used both simple ratio and effect modifier approaches to SCCS with active comparators to obtain comparator adjusted estimates.Results: A total of 2802 and 1889 people with MI who had exposure to PPIs and H2RA were included respectively. We observed a higher risk of MI during days 1-14 following the start of PPI prescription (Incidence rate ratio (IRR): 2.30, 95% confidence interval (CI): 1.76-3.00) versus baseline. Similarly, we observed a higher risk of MI during days 1-14 following the start of H2RA prescription (IRR: 2.46, 95%CI: 1.92-3.16) versus baseline. In the novel SCCS analyses, comparator adjusted estimates were 0.93 (95%CI: 0.57-1.30) and 0.83 (95%CI: 0.58-1.20) during days 1-14 in simple ratio and effect modifier approach, respectively.Conclusions: We observed no difference in risk of MI associated with PPIs compared with baseline using H2RA as the active comparator. The elevated risk of MI associated with PPIs is likely due to protopathic bias. More studies are required to explore the feasibility of using active comparators in SCCS to address protopathic bias in addition to confounding. [ABSTRACT FROM AUTHOR]

Background: Elevated concentrations of low-density lipoprotein cholesterol (LDL-C) are an important cause of recurrent cardiovascular events. This study aimed to describe the distribution and achieved concentrations of LDL-C among patients with myocardial infarction (MI), percutaneous coronary intervention (PCI), stroke, or transient ischaemic attack (TIA) in Hong Kong. Methods: Patients with a lipid test from a public hospital were identified from the Clinical Database and Analysis Reporting System of the Hong Kong Hospital Authority. Among patients with an inpatient hospitalization for MI, PCI, stroke or TIA, between 2003 to 2016, the distribution of LDL-C levels and the number (%) of patients achieving an absolute concentration of LDL-C <1.8 mmol/L at baseline (in-hospital) and during 12 months after hospital discharge were described. Results: A total of 18417 patients were included (mean [SD] age, 70.0 [12.9] years; male, 60.3%), of which 3637 had MI, 4096 had PCI, and 10684 had stroke or TIA. At hospital discharge 12082 (65.6%) patients were prescribed statins, 690 (3.7%) were prescribed nonstatins, and 1849 (10.0%) achieved an LDL-C <1.8 mmol/L. Overall, 5654 (30.7%) patients did not have LDL-C result available within 12 months of discharge (MI, 605 [16.6%]; PCI, 432 [10.5%]; stroke or TIA, 4617 [43.2%]). Among the overall cohort, 4591 (24.9%) patients achieved an LDL-C <1.8 mmol/L during 12 months of follow-up (MI, 1288 [35.4%]; PCI, 1542 [37.6%]; stroke or TIA, 1761 [16.5%]). Improvements in achieved LDL-C were observed over time with a mean LDL-C 2.64 (0.92) mmol/L and 20.0% of patients achieving an LDL-C <1.8 mmol/L in 2003 as compared with a mean LDL-C 1.86 (0.70) mmol/L and 53.9% of patients achieving an LDL-C <1.8 mmol/L in 2016. Conclusions: In this single centre cohort study from Hong Kong, nearly half of patients with MI, PCI, or stroke in 2016 appear to qualify for intensification of lipid-modifying drug treatment in order to achieve a treatment goal of LDL-C<1.8 mmol/L. Further research is required in Hong Kong to assess contemporary management of LDL-C in a larger group of patients with established atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. Methods This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. Results Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67–29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12–9.51) and 21.22 (95% CI, 13.78–32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38–12.53) and 37.32 (95% CI, 26.98–51.25) per 100 000 persons vaccinated. Conclusions There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to determine trends and patterns of symptomatic medication used against dementia in 66 countries and regions. Methods: This was a cross‐sectional study that used the wholesale data from the IQVIA Multinational Integrated Data Analysis System database. Sale data for symptomatic medication against dementia from 66 countries and regions from 2008 to 2018 were analysed and stratified by income level (low/middle‐income countries [LMICs], n = 27; high‐income countries [HICs], n = 37; regions, n = 2). The medication use volume was estimated by defined daily dose (DDD) per 1000 inhabitants per day (World Health Organization DDD harmonized the size, strength and form of each pack and reflects average dosing). Changes in medication use over time were quantified as percentage changes in compound annual growth rates (CAGRs). Results: Total symptomatic medication against dementia sales increased from 0.85 to 1.33 DDD per 1000 inhabitants per day between 2008 and 2018 (LMICs 0.094–0.396; HICs 3.88–5.04), which is an increase of CAGR of 4.53% per year. The increase was mainly driven by the LMICs (CAGR = 15.42%) in comparison to the HICs (CAGR = 2.65%). The overall medication use from 2008 to 2018 increased for all four agents: memantine (CAGR = 8.51%), rivastigmine (CAGR = 6.91%), donepezil (CAGR = 2.72%) and galantamine (CAGR = 0.695%). In 2018, the most commonly used medication globally was donepezil, contributing to 49.8% of total use volume, followed by memantine (32.7%), rivastigmine (11.24%) and galantamine (6.36%). Conclusion: There was an increasing trend in the use of symptomatic medications against dementia globally, but the use remained low in LMICs. Interventions may be needed to support the medication use in some countries. [ABSTRACT FROM AUTHOR]