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Low-dose aspirin and metformin have been individually associated with a reduced risk of cancer. Whether their concurrent use in adults with type 2 diabetes mellitus (T2DM) is associated with a reduced risk of colorectal cancer (CRC) is unclear.Among individuals with T2DM taking metformin, we sought to evaluate the association between low-dose aspirin versus no aspirin and the risk of CRC.A multiple-database new-user cohort study of patients with T2DM taking metformin was conducted between 2007-2010 (Clinical Data Analysis and Reporting System [CDARS], Hong Kong) and 2007-2016 (The Health Improvement Network [THIN], UK). The primary outcome was incident CRC. Patients were followed from index date of prescription until the earliest occurrence of an outcome of interest, an incident diagnosis of any cancer, death, or until December 31, 2019. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Estimates were pooled using an inverse variance random effects model, and heterogeneity was assessed using IAfter one-to-one propensity-score matching, 57,534 patients were included (CDARS = 16,276; THIN = 41,258). The median (IQR) follow-up was 9.3 (6.5-10.7) years in CDARS and 3.2 (1.1-5.8) years in THIN. The concurrent use of low-dose aspirin and metformin was not associated with a lower risk of CRC compared to metformin only (HR = 0.89, 95% CI 0.75-1.05, ILow-dose aspirin was not associated with a lower risk of CRC in patients with T2DM taking metformin. Our study does not support the routine use of low-dose aspirin in this population. This article is protected by copyright. All rights reserved.

Background Oral anticoagulants (OACs) are high-risk medications often used in older people with complex medication regimens. This study was the first to assess the association between overall regimen complexity and bleeding in people with atrial fibrillation (AF) initiating OACs. Methods Patients diagnosed with AF who initiated an OAC (warfarin, dabigatran, rivaroxaban, apixaban) between 2010 and 2016 were identified from the Hong Kong Clinical Database and Reporting System. Each patient’s Medication Regimen Complexity Index (MRCI) score was computed. Baseline characteristics were balanced using inverse probability of treatment weighting. People were followed until a first hospitalization for bleeding (intracranial hemorrhage, gastrointestinal bleeding, or other bleeding) and censored at discontinuation of the index OAC, death, or end of the follow-up period, whichever occurred first. Cox regression was used to estimate hazard ratios (HR) between MRCI quartiles and bleeding during initiation and all follow-up. Results There were 19 292 OAC initiators (n = 9 092 warfarin, n = 10 200 direct oral anticoagulants) with a mean (standard deviation) age at initiation of 73.9 (11.0) years. More complex medication regimens were associated with an increased risk of bleeding (MRCI > 14.0–22.00: aHR 1.17, 95% confidence interval [CI] 0.93–1.49; MRCI > 22.0–32.5: aHR 1.32, 95%CI 1.06–1.66; MRCI > 32.5: aHR 1.45, 95%CI 1.13–1.87, compared to MRCI ≤ 14). No significant association between MRCI and bleeding risk was observed during the initial 30, 60, or 90 days of treatment. Conclusion In this cohort study of people with AF initiating an OAC, a more complex medication regimen was associated with higher bleeding risk over periods longer than 90 days. Further prospective studies are needed to assess whether MRCI should be considered in OAC prescribing.

Aims Concern about the cardiovascular safety of coronavirus disease 2019 (COVID-19) vaccines among individuals with cardiovascular disease (CVD) may lead to vaccine hesitancy. We sought to assess the association between two COVID-19 vaccines, BNT162b2 and CoronaVac, and the risk of major adverse cardiovascular events (MACE) in individuals with established CVD. Methods and results We identified individuals with a history of CVD before 23 February 2021 and a diagnosis of MACE between 23 February 2021 and 31 January 2022 in Hong Kong. MACE was defined as a composite of myocardial infarction, stroke, revascularization, and cardiovascular death. Electronic health records from the Hong Kong Hospital Authority were linked to vaccination records from the Department of Health. A self-controlled case-series method was used to evaluate the risk of MACE for 0–13 and 14–27 days after two doses of COVID-19 vaccine. We estimated incidence rate ratios (IRRs) to compare the risk of MACE between each risk period and the baseline period. A total of 229 235 individuals with CVD were identified, of which 1764 were vaccinated and had a diagnosis of MACE during the observation period (BNT162b2 = 662; CoronaVac = 1102). For BNT162b2, IRRs were 0.48 [95% confidence interval (CI) 0.23–1.02] for the first dose and 0.87 (95% CI 0.50–1.52) for the second dose during the 0–13 days risk period, 0.40 (95% CI 0.18–0.93) for the first dose and 1.13 (95% CI 0.70–1.84) for the second dose during the 14–27 days risk period. For CoronaVac, the IRRs were 0.43 (95% CI 0.24–0.75) for the first dose and, 0.73 (95% CI 0.46–1.16) for the second dose during the 0–13 days risk period, 0.54 (95% CI 0.33–0.90) for the first dose and 0.83 (95% CI 0.54–1.29) for the second dose during the 14–27 days risk period. Consistent results were found in subgroup analyses for different sexes, age groups and different underlying cardiovascular conditions. Conclusion Our findings showed no evidence of an increased risk of MACE after vaccination with BNT162b2 or CoronaVac in patients with CVD. Future research is required to monitor the risk after the third dose of each vaccine.

Background and aims Lipid-modifying agents (LMAs) are increasingly used to reduce lipid levels and prevent cardiovascular events but the magnitude of their consumption in different world regions is unknown. We aimed to describe recent global trends in LMA consumption and to explore the relationship between country-level LMA consumption and cholesterol concentrations. Methods This cross-sectional and ecological study used monthly pharmaceutical sales data from January 2008 to December 2018 for 83 countries from the IQVIA Multinational Integrated Data Analysis System and total and non-high-density lipoprotein (non-HDL) cholesterol concentrations from the NCD Risk Factor Collaboration. Compound annual growth rate (CAGR) was used to assess changes in LMA consumption over time. Results From 2008 to 2018, use of LMAs increased from 7468 to 11,197 standard units per 1000 inhabitants per year (CAGR 4.13%). An estimated 173 million people used LMAs in 2018. Statins were the most used class of LMA and their market share increased in 75% of countries between 2008 and 2018. From 2013 to 2018, consumption of low-density lipoprotein lowering therapies increased (statins 3.99%; ezetimibe 4.01%; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors 104.47%). Limited evidence supports a clear relationship between country-level changes in LMA consumption and mean total and non-HDL cholesterol concentrations in 2008 versus 2018. Conclusions Since 2008, global access to LMAs, especially statins, has improved. In line with international lipid guideline recommendations, recent trends indicate growth in the use of statins, ezetimibe, and PCSK9 inhibitors. Country-level patterns of LMA use and total and non-HDL cholesterol varied considerably.

Evidence of the effectiveness of statins compared with fibrates for primary prevention of cardiovascular events is limited. Therefore, we assessed the comparative effectiveness of simvastatin versus gemfibrozil for primary prevention of major adverse cardiovascular events (MACE) and mortality.This territory-wide cohort study used electronic health records of simvastatin and gemfibrozil prescriptions from the Hong Kong Hospital Authority and compared simvastatin or gemfibrozil initiation. The primary outcome was MACE, defined as the composite of the first diagnosis of cardiovascular mortality, coronary heart disease, or stroke. Secondary outcomes were the individual components of MACE, all-cause mortality, and non-cardiovascular mortality. Inverse probability of treatment weighting on the propensity score was used to estimate hazard ratios (HRs).A total of 223,699 individuals (120,207 [53.7%] women; median follow-up 7.0 years [interquartile range 5.7-9.1]) who were prescribed simvastatin (n = 168,630) or gemfibrozil (n = 55,069) were included. Simvastatin was associated with a reduced risk of MACE (HR 0.90, 95% confidence interval [CI] 0.88-0.93), all-cause mortality (HR 0.88, 95% CI 0.86-0.90), cardiovascular mortality (HR 0.71, 95% CI 0.67-0.76), and non-cardiovascular mortality (HR 0.92, 95% CI 0.89-0.95). Associations for MACE varied according to baseline characteristics with gemfibrozil being associated with a reduced risk of MACE in men and patients with low baseline high-density lipoprotein (HDL) cholesterol ( 1.0 mmol/L).The results of this study showed better population-level effectiveness of simvastatin compared with gemfibrozil for the primary prevention of MACE; however, a definitive randomized controlled trial is required to compare simvastatin with gemfibrozil among patients with low HDL cholesterol, as they appear to obtain benefit with gemfibrozil.

Risk of suicide attempt, depression, anxiety and seizure and the association with statins is an ongoing debate. We aim to investigate the association between statins and the above neuropsychological outcomes, in specific pre- and post-exposure time windows.We identified patients aged 40-75 years old who were dispensed a statin between January 1, 2003 and December 31, 2012 from the Hong Kong Clinical Data AnalysisReporting System (CDARS), an electronic medical records database. Patients with new onset of suicide attempt, depression, anxiety and seizure were derived from the original dataset separately, in a self-controlled case series study design. A non-parametric spline-based self-controlled case series model was built to measure continuous changes of risk.We identified 396,614 statin users. The risk of each outcome was elevated prior to statin initiation with incidence rate ratios of 1.38 (95 % CI, 1.09-1.74) for suicide attempt, 1.29 (95 % CI, 1.15-1.45) for depression, 1.35 (95 % CI, 1.19-1.53) for anxiety, and 1.45 (95 % CI, 1.21-1.73) for seizure. The incidence rate ratios remained elevated after the initiation of statins during the first 90 and 91-365 days after statin prescription and decreased to the baseline level after 1 year of continuous prescription.CDARS includes prescription data but not adherence data, which could lead to misclassification of exposure periods.Our study does not support a direct association between statin use and suicide attempt, depression, anxiety and seizure, whose risks could be explained by cardiovascular events, for which statins were prescribed.

Neuroleptic malignant syndrome (NMS) is a rare and acute adverse drug reaction associated with antipsychotic therapy. However, few data on the risk and epidemiology of NMS are available. The aim of this study was to ascertain the incidence risk and all-cause mortality of NMS associated with antipsychotic use, and to assess the association of recent antipsychotic exposure and NMS. We did a population-based study using data from the Hong Kong Hospital Authority’s Clinical Data Analysis and Reporting System database. Cases had a first diagnosis of NMS between 1 January 2004 and 30 November 2017. A case-crossover analysis was used to compare antipsychotic exposure 30 days before the diagnosis of NMS (index date) and a reference period 91–120 days before the index date. To adjust for potential time trends in antipsychotic exposure, we sampled from cases to match current cases and future cases, and further adjusted for select medications and acute medical conditions. 297,647 patients were prescribed antipsychotics, and the incidence risk of NMS was 0.11%. Of the 336 cases included in the case-crossover analysis, 20 (6%) died within 30 days after the index date; only one case had NMS recorded as the primary cause of death. When compared with the reference period, cases were more frequently prescribed multiple antipsychotics (15.8% vs 26.8%; standardized mean difference [SMD] 0.27) and short-acting injectable antipsychotics (3.6% vs 13.7%; SMD 0.37) during the 30 days prior to the diagnosis of NMS. Odds ratios for antipsychotic exposure in the case-crossover, case-crossover adjusted for time trend, and case-crossover adjusted for time trend and potential confounders analysis were 8.00 (95% confidence interval 3.42–18.69), 5.88 (2.46–14.04), and 4.77 (1.95–11.66). Our results suggest that recent use of antipsychotics is associated with NMS. Although a case-only design inherently controls for confounding by time-invariant factors, residual confounding by acute medical conditions with similar presentations to NMS cannot be fully excluded.

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

BackgroundBerberine is a nutraceutical that may improve lipid profiles. Berberine may also affect sex hormones and exert sex-specific effects, which has been overlooked.ObjectivesTo comprehensively review the efficacy and safety of lipid-lowering effect of berberine with consideration of potential sex disparity.MethodsEligible studies were randomized controlled trials in adults that compared berberine versus placebo and measured blood lipids or lipoproteins. Studies were identified from Medline, Embase, Wanfang, CNKI, two clinical trial registries and previous systematic reviews. Mean differences (MD) were estimated using inverse variance weighting with random effects models. Risk of bias was assessed using the Cochrane risk of bias tool for randomized trials.Results16 studies were included with treatment of 4 to 24 weeks. Berberine reduced low-density lipoprotein (LDL) cholesterol (−0.45 mmol/L, 95% CI -0.60 to -0.31, 12 studies, n=1,224), total cholesterol (−0.47 mmol/L, 95% CI -0.61 to -0.33, 15 studies, n=1,397), triglycerides (−0.32 mmol/L, 95% CI -0.44 to -0.19, 16 studies, n=1,421) and apolipoprotein B (−0.25 mg/dL, 95% CI -0.40 to -0.11, 2 studies, n=127). Berberine increased high-density lipoprotein (HDL) cholesterol by 0.06 mmol/L (95% CI 0.00 to 0.12, 13 studies, n=1,248). Notably, the effect on HDL cholesterol was different in women (0.11 mmol/L, 95% CI 0.09 to 0.13) from that in men (−0.07 mmol/L, 95% CI -0.16 to 0.02). Gastrointestinal adverse events were the most frequently reported adverse events.ConclusionsBerberine decreased LDL cholesterol, triglycerides, and apolipoprotein B, with a potential sex-specific effect on HDL cholesterol. Large-scale trials considering sex disparity are required.

Refereed/Peer-reviewed Objective: We aimed to assess whether the introduction of the first infliximab biosimilar was associated with changes in overall infliximab consumption (originator and biosimilars) and price changes to the originator infliximab. Methods: An interrupted time series analysis using infliximab sales data from 2010 to 2020 from the IQVIA Multinational Integrated Data Analysis System for eight selected regions: Australia, Canada, Hong Kong, Korea, India, Japan, the UK, and the USA. Quarterly measures of infliximab consumption and list prices were respectively defined as the number of standard units (SU)/1000 inhabitants and as 2020 USA dollars (USD)/SU. Results: Following the introduction of infliximab biosimilars, overall infliximab consumption increased in Australia [immediate change: 0.145 SU/1000 inhabitants (P = 0.014); long-term change: 0.022 SU/1000 inhabitants per quarter (P < 0.001)], Canada [immediate change 0.415 (P = 0.008)], the UK [long-term change 0.024 (P < 0.001)], and Hong Kong [immediate change: 0.042 (P < 0.001)]. The list price of originator infliximab also decreased following biosimilar introduction in Australia [immediate change: − 187.84 USD/SU (P < 0.001); long-term change − 6.46 USD/SU per quarter (P = 0.043)], Canada [immediate change: − 145.58 (P < 0.001)], the UK [immediate change: − 34.95 (P = 0.010); long-term change: − 4.77 (P < 0.001)], and Hong Kong [long-term change: − 4.065 (P = 0.046)]. Consumption and price changes were inconsistent in India, Japan, Korea, and the USA. Conclusions: Introduction of the first infliximab biosimilar was not consistently associated with increased consumption across regions. Additional policy and healthcare system interventions to support biosimilar infliximab adoption are needed.

Background Variability in low-density lipoprotein cholesterol (LDL-C) response to statins is underappreciated. We characterised patients by their statin response (SR), baseline risk of cardiovascular disease (CVD) and 10-year CVD outcomes. Methods and results A multivariable model was developed using 183,213 United Kingdom (UK) patients without CVD to predict probability of sub-optimal SR, defined by guidelines as Conclusions Patients with sub-optimal response to statins experienced significantly more MACE, regardless of baseline CVD risk. To enhance cholesterol management for primary prevention, statin response should be considered alongside risk assessment.

Haloperidol remains a frequently prescribed first-generation antipsychotic. However, haloperidol-associated mortality risk by all causes, cardiovascular disease (CVD), and pneumonia compared with other antipsychotics is unknown. This study investigated the mortality risk associated with long-term haloperidol treatment versus that with other antipsychotics. We identified incident antipsychotic users from 2004 to 2014 in the Clinical Data Analysis and Reporting System (CDARS), a population-based clinical database managed by the Hong Kong Hospital Authority. We included patients who were aged ≥ 18 and received antipsychotics for any indication apart from terminal illnesses or management of acute behavioural disturbance. Patients on haloperidol and other antipsychotic agents (risperidone, quetiapine, olanzapine, chlorpromazine, aripiprazole, sulpiride, amisulpride, or trifluoperazine) were matched by propensity score. Hazard ratios (HRs) for all-cause mortality and death due to CVD and pneumonia were estimated with 95% confidence intervals (CIs) using a Cox proportional hazards model. In total, 136,593 users of antipsychotics were included. During a mean follow-up of 3.2 years, the incidence of all-cause mortality ranged from 186.8/1000 person-years for haloperidol to 10.4/1000 person-years for trifluoperazine. The risk of all-cause mortality was lower with non-haloperidol antipsychotics than with haloperidol, with HRs ranging from 0.68 (95% CI 0.64–0.72 [chlorpromazine]) to 0.43 (95% CI 0.36–0.53 [trifluoperazine]). Risperidone, quetiapine, sulpiride, chlorpromazine, aripiprazole, and trifluoperazine were associated with a significantly lower risk of pneumonia-related mortality. A significantly lower risk of CVD mortality was observed for risperidone, sulpiride, chlorpromazine, and quetiapine. Haloperidol was associated with increased overall mortality when compared with other antipsychotics in long-term follow-up. Treatment with haloperidol should be carefully considered, especially in older patients and patients at risk of CVD or pneumonia, since the risk of death appears to be lower with non-haloperidol agents.

The impact of substance use disorders (SUD) in an Asian population has not been fully explored. We aimed to assess the risk of mortality, accident and emergency (AE) department attendances, and hospital admissions associated with SUD in a population-based cohort study.Patients diagnosed with SUD in public AE departments from 2004 to 2016 (N = 8,423) were identified in the Clinical Database Analysis and Reporting System of the Hong Kong Hospital Authority and 1:1 matched to patients without SUD by propensity score (N = 6,074 in each group). Relative risks of mortality, AE attendances and hospital admissions were assessed using Cox regression and Hurdle negative binomial regression.Patients with SUD had higher mortality (hazard ratio=1.43; 95% confidence interval [CI]=1.26-1.62) and more often died from poisoning or toxicity and injuries. The odds ratio (OR) for AE attendances and all-cause hospital admissions associated with SUD were 2.80 (95% CI=2.58-3.04) and 3.54 (95% CI=3.26-3.83), respectively. The impact of SUD on the above outcomes was greatest among school-aged individuals (≤ 21 years) and decreased with age. The relative risk of mental disorder-related hospital admissions was much higher than that for infections, respiratory diseases, and cardiovascular diseases. In patients with SUD, ketamine and amphetamine use were associated with increased AE attendances than opioid use.SUD was associated with increased mortality, AE attendances and hospital admissions, especially in school-aged individuals. Our findings suggest prioritising early treatment and preventive interventions for school-aged individuals and focusing on the management of comorbid mental disorders and the use of ketamine and amphetamine.

The WHO Comprehensive Mental Health Action Plan 2013-2030 encourages routine collection and reporting of a set of essential mental health indicators, including the availability of psychotropic medicines. The global monitoring of country-level psychotropic medicine consumption trends can provide information on the extent of the availability of psychotropic medicines. The primary objective of this study was to investigate global trends in psychotropic medicines consumption from 2008 to 2019 across 65 countries and regions according to country income level and geographical region.In this longitudinal trends study, we used pharmaceutical sales data from the IQVIA-Multinational Integrated Data Analysis System (IQVIA-MIDAS). We analysed monthly sales data of psychotropic medicines between Jan 1, 2008, and Dec 31, 2019. Total psychotropic medicine consumption included sales of antidepressants, antipsychotics, tranquilisers, sedatives or hypnotics, and mood stabilisers. Population estimates of each country or region (eight lower-middle-income countries, 19 upper-middle-income countries, and 38 high-income countries) were based on the UN World Population Prospects 2019 report. Average annual sales trends of psychotropic medicines, expressed as defined daily dose (DDD) per 1000 inhabitants per day, were estimated using a random-effects model adjusted for income level and region. Relative changes in the annual consumption of psychotropic medicines by income, expressed as DDD per 1000 inhabitants per day, were assessed as percentage change for each medicine class.Psychotropic medicine sales increased from 28·54 DDD per 1000 inhabitants per day in 2008 to 34·77 DDD per 1000 inhabitants per day in 2019, corresponding to a 4·08% (95% CI 2·96-5·21) relative average increase annually. The absolute annual increase was greater in high-income countries (3·31 DDD per 1000 inhabitants per day, 95% CI 3·01-3·61) compared with upper-middle-income countries (1·94 DDD per 1000 inhabitants per day, 1·45-2·44) and low-middle-income countries (0·88 DDD per 1000 inhabitants per day, 0·62-1·13; p0·0001). The relative average annual increase in psychotropic medicine sales from 2008 to 2019 was greater in upper-middle-income countries (7·88%, 95% CI 6·99-8·77) than in lower-middle-income countries (2·90%, 2·40-3·39) and high-income countries (1·02%, 0·80-1·24). In 2019, the regional consumption of psychotropic medicines varied greatly, with the highest sales of all psychotropic medicine classes reported in northern America (167·54 DDD per 1000 inhabitants per day) and lowest sales reported in Asia (5·59 DDD per 1000 inhabitants per day). 17 countries had very low consumption of psychotropic medicines in 2019, including high-income countries and countries with a high prevalence of mental disorders.The consumption of psychotropic medicines has increased over a 12-year period, and although the absolute growth rate was highest in high-income countries, the relative growth is highest in middle-income countries and especially upper-middle-income countries. Disparities in psychotropic medicine consumption of countries can only partly be explained by geographical location and income. Greater efforts are needed to increase the availability of psychotropic medicines in countries with very low consumption, which is probably due to financial or cultural reasons as well as scarcity of trained health-care professionals to prescribe psychotropic medicines.None.

AimsLipid-modifying agents (LMAs) are increasingly used to reduce lipid levels and prevent cardiovascular events, but the magnitude of their consumption in different world regions is unknown. We aimed to describe recent global trends in LMA consumption and to explore the relationship between country-level LMA consumption and cholesterol concentrations.Methods and resultsThis cross-sectional and ecological study used monthly pharmaceutical sales data from January 2008 to December 2018, for 83 countries from the IQVIA Multinational Integrated Data Analysis System, and total and non–high-density lipoprotein (non– HDL) cholesterol concentrations from the NCD Risk Factor Collaboration. The compound annual growth rate (CAGR) was used to assess changes in LMA consumption over time. From 2008 to 2018, the use of LMAs increased from 7,468 to 11,197 standard units per 1000 inhabitants per year (CAGR 4.13%). Statins were the most used class of LMA and their market share increased in 75% of countries between 2008 and 2018. Fibrates were the most consumed nonstatin drugs. From 2013 to 2018, consumption of low-density lipoprotein lowering therapies increased (statins 3.99%; ezetimibe 4.01%; proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors 104.47%). Limited evidence supports a clear relationship between country-level changes in LMA consumption and total and non–HDL cholesterol concentrations in 2008 versus 2018.ConclusionSince 2008, global access to LMAs, especially statins, has improved. In line with international lipid guideline recommendations, recent trends indicate growth in the use of statins, ezetimibe, and PCSK9 inhibitors. Country-level patterns of LMA use and total and non–HDL cholesterol varied considerably.

Objective To assess whether in adults with dyslipidemia, statins reduce cardiovascular events, mortality, and adverse effects when compared to fibrates. Methods Systematic review and meta-analysis of head-to-head randomized trials of statin and fibrate monotherapy. MEDLINE, EMBASE, Cochrane, WHO International Controlled Trials Registry Platform, and ClinicalTrials.gov were searched through October 30, 2019. Trials that had a follow-up of at least 28 days, and reported mortality or a cardiovascular outcome of interest were eligible for inclusion. Efficacy outcomes were cardiovascular mortality and major cardiovascular events. Safety outcomes included myalgia, serious adverse effects, elevated serum creatinine, and elevated serum alanine aminotransferase. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using the Mantel-Haenszel fixed-effect model, and heterogeneity was assessed using the I2 statistic. Results We included 19 eligible trials that directly compared statin and fibrate monotherapy and reported mortality or a cardiovascular event. Studies had a limited duration of follow-up (range 10 weeks to 2 years). We did not find any evidence of a difference between statins and fibrates for cardiovascular mortality (OR 2.35, 95% CI 0.94–5.86, I2 = 0%; ten studies, n = 2657; low certainty), major cardiovascular events (OR 1.15, 95% CI 0.80–1.65, I2 = 13%; 19 studies, n = 7619; low certainty), and myalgia (OR 1.32, 95% CI 0.95–1.83, I2 = 0%; ten studies, n = 6090; low certainty). Statins had less serious adverse effects (OR 0.57, 95% CI 0.36–0.91, I2 = 0%; nine studies, n = 3749; moderate certainty), less elevations in serum creatinine (OR 0.17, 95% CI 0.08–0.36, I2 = 0%; six studies, n = 2553; high certainty), and more elevations in alanine aminotransferase (OR 1.43, 95% CI 1.03–1.99, I2 = 44%; seven studies, n = 5225; low certainty). Conclusions The eligible randomized trials of statins versus fibrates were designed to assess short-term lipid outcomes, making it difficult to have certainty about the direct comparative effect on cardiovascular outcomes and mortality. With the exception of myalgia, use of a statin appeared to have a lower incidence of adverse effects compared to use of a fibrate.

BackgroundClinical guidelines recommend specific targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) for primary prevention of cardiovascular disease (CVD). Furthermore, individual variability in lipid response to statin therapy requires assessment of the association in diverse populations.AimTo assess whether lower concentrations of LDL-C and non-HDL-C are associated with a reduced risk of major adverse cardiovascular events (MACE) in primary prevention of CVD.Design & settingAn international, new-user, cohort study will be undertaken. It will use data from three electronic health record databases from three global regions: Clinical Practice Research Datalink, UK; PREDICT-CVD, New Zealand (NZ); and the Clinical Data and Analysis Reporting System, Hong Kong (HK).MethodNew statin users without a history of atherosclerotic CVD, heart failure, or chronic kidney disease, with baseline and follow-up lipid levels will be eligible for inclusion. Patients will be classified according to LDL-C (ConclusionResults will inform clinicians about the benefits of achieving guideline recommended concentrations of LDL-C for primary prevention of CVD.

COVID-19 has required universities to rapidly develop vaccination policies for students and staff, yet little is known about the preferences of these individuals toward vaccination.To quantify student and staff preferences for COVID-19 vaccination at a university in Hong Kong.A cross-sectional online survey study was conducted from July 20 to September 21, 2021, before the announcement of a campus-wide vaccine mandate. A survey of 42 451 eligible university students and staff used discrete-choice experiment methods to quantify 7 attributes of COVID-19 vaccination: risk of a mild or moderate adverse event after vaccination, risk of a severe adverse event after vaccination, efficacy against COVID-19 infection, efficacy against severe manifestation of COVID-19 infection, duration of protection after vaccination, incentive for completing vaccination, and out-of-pocket costs.A mixed logit regression model was used to estimate the preferences of attributes for COVID-19 vaccines and marginal willingness to pay (mWTP) adjusted for background characteristics, role, vaccination, and COVID-19 infection status of family or friends, adverse event status after vaccination among family and friends of participants, and scenario block.Among 42 451 eligible university students and staff invited, 3423 individuals completed the survey (mean [SD] age, 27.1 [9.9] years; 2053 [60.0%] women). Participants included 2506 students (73.2%) and 917 staff (26.8%), with a response rate of 8.1%. Quarantine-free travel was preferred (β = 0.86; 95% CI, 0.72-0.99; mWTP: $235.9; 95% CI, $190.3-$294.2), followed by efficacy against any COVID-19 infection (β = 0.30; 95% CI, 0.29-0.32; mWTP: $84.1; 95% CI, $71.8-$100.8), against severe manifestation of COVID-19 infection (β = 0.25; 95% CI, 0.24-0.27; mWTP: $69.7; 95% CI, $465-$653), and risk of severe adverse events following vaccination (β = -0.24; 95% CI, -0.27 to -0.21; mWTP: -$66.8; 95% CI, -$81.5 to -$55.3). Participants were less concerned about protection duration (β = 0.17; 95% CI, 0.15-0.18; mWTP: $46.0; 95% CI, $38.6-$56.2) and risk of mild to moderate adverse events (β = -0.12; 95% CI, -0.13 to -0.10; mWTP: -$32.7; 95% CI, -$41.2 to -$26.4).Preference of all attributes were significant and were considered important by the participants for vaccine decision-making. Insights drawn could assist policy makers in future vaccination decisions, such as campus vaccine mandate and requirement of a third dose.

Background: Neuroleptic malignant syndrome (NMS), a rare but serious adverse reaction of antipsychotics, however, the little evidence risk and epidemiology of NMS is available. We aimed to determine the risk of NMS associated with exposure to any antipsychotic, and four antipsychotics commonly implicated in cases of NMS: haloperidol, olanzapine, quetiapine, and risperidone. To characterize the incidence and case fatality risk of NMS in patients taking antipsychotics. Methods: We conducted a population-based cohort analyzing health records of 297 647 antipsychotic users identified from January 1st, 2004 to December 31st, 2016 and 328 in patients with incident diagnosis of NMS during the same period, to measure the incidence and case fatality risk of NMS. We further extended the NMS identification period to November 30th, 2017 and conducted a case-crossover study analyzing data for a total of 336 eligible patients to estimate the risk of NMS associated with any antipsychotic, haloperidol, olanzapine, quetiapine, and risperidone, by comparing the use of antipsychotics during day 1 to 30 (case period) and day 91 to 120 (reference period) preceding the diagnosis of NMS. Findings: In the case-crossover study, 336 patients were diagnosed with NMS (210 males [62.5%]; mean age, 49.7 years; case fatality risk 6.0%). After adjustment for time trends in exposure, concurrent medications, and medical conditions, diagnosis of NMS was associated with exposure to any antipsychotic (OR, 4.77; 95% CI, 1.95-11.66), haloperidol (OR, 4.40; 95% CI 1.97-9.81), and quetiapine (OR, 4.32; 95% CI, 1.70-10.97), while there was no observed association for risperidone (OR, 2.00; 95% CI, 0.93-4.32) or olanzapine (OR, 1.23; 95% CI, 0.47-3.18). In the cohort of patients exposed to antipsychotics, NMS occurred with an incidence of 1.10 per 1000 persons. Interpretation: Antipsychotics are associated with an acutely increased risk of NMS. Patients had statistically significant increased odds of exposure to, haloperidol and quetiapine but not risperidone or olanzapine, during the 30 days prior to the diagnosis of NMS, as compared with the earlier reference period. Clinicians who prescribe antipsychotics should weigh the acutely increased risk of NMS with the potential benefits of antipsychotic therapy, especially for haloperidol and quetiapine. Funding: Early Career Scheme, Research Grants Council, Hong Kong. Declaration of Interest: This study was partially funded by Early Career Scheme, Research Grants Council, Hong Kong (project reference 789813) received by Esther W Chan. All authors declare that no other support has been received from any organization for the submitted work; no other financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted study. Ethical Approval: Research ethics approval was obtained from the Institutional Review Board of The University of Hong Kong/Hospital Authority HKWC (Reference Number: UW 15-619).

Up-to-date data on the burden of disease are important to identify patients with unmet needs and to optimize healthcare resources. We aimed to characterize the burden of pneumonia hospitalizations in Hong Kong and inform targeted healthcare policies for pneumonia control in the era of global aging. This was a population-based study using a territory-wide administrative electronic health record system that covers all public hospitals of Hong Kong. Patients admitted to public hospitals, from 2011 to 2015, with a diagnosis of pneumonia at discharge were identified based on the International Classification of Diseases-Ninth Revision-Clinical Modification Codes (480–486 and 487.0). Incidence, inpatient case-fatality, all-cause fatality, 28-day readmission, hospital length of stay, and healthcare costs were assessed for seven age strata. We identified 323,992 patients (median age 80 years, 44.4% female) with hospitalized pneumonia (organism unspecified 84.2%; bacterial pneumonia 12.3%; viral pneumonia 2.5%; others 1.0%). Annual incidence was 955.1 per 100,000 population, with a 10.6% decrease from 2011 to 2015. Case-fatality, all-cause fatality, and 28-days readmission risks were 13.8, 21.6, and 19.5%, respectively. The average hospital length of stay was 14.1 days with corresponding direct costs of $9348 USD per episode in the monetary value of 2015. Individuals aged ≥ 65 years accounted for over 75% of pneumonia-related hospitalizations, 90% of deaths, and the majority of healthcare costs. Hospitalized pneumonia represents a considerable health and economic burden in Hong Kong, especially in older adults. The study provides a population-level baseline estimate for further cost-effective evaluation of targeted strategies for pneumonia control.

Background and aims Clinical practice guidelines recommend specific statin doses for the primary and secondary prevention of cardiovascular disease. Little is known about how statin utilization and dosing have evolved over time in Hong Kong. The aim of this study was to describe trends in statin prevalence, initiation, and dosing from 2004 to 2015. Methods Patients receiving public health services, who were prescribed a statin, were included if they received a lipid test at a single center (n = 58,672). Using the territory-wide electronic health record, prescribed daily statin dose, nondaily dose frequency, and statin dose intensity were determined for statin prescriptions from 2004 to 2015. Statin prescription prevalence and initiation rates were estimated using the appropriate at-risk population in the hospital catchment area as the denominator. Prescribed daily doses were stratified by primary or secondary cardiovascular prevention status to assess changes in statin dosing over time. Results The prescription prevalence of statins was higher in 2015 (8.68%; 95% CI, 8.60%–8.75%) as compared with 2004 (1.82%; 95% confidence interval [CI], 1.78%–1.86%). Initiation rates for new statin users increased from 2004 to 2013. High-intensity statins were infrequently prescribed. New users generally had higher statin initiation rates for primary prevention. There were small increases in the prescribed daily doses of statins. Nondaily statin dosing was infrequent (0.42% of all prescriptions). Conclusions The prevalence and initiation of statin prescriptions increased in Hong Kong, and was in part driven by low-intensity statins for the primary prevention of cardiovascular disease.