Antibiotic use is common among people living with dementia (major neurocognitive disorder) and is associated with seizures and other neuropsychiatric disorders. This population-based cohort study aims to understand the association of repeated antibiotic prescriptions with seizure-related, other neuropsychiatric disorders-related and all-cause hospitalization among people living with dementia, using electronic health records from the Hong Kong Clinical Data Analysis Reporting System. There were 79,367 patients with dementia who were aged 65 or older and had seizure-related high-risk antibiotic prescriptions from 2004 to 2019. There were 71,920 patients with dementia who had other neuropsychiatric disorders-related high-risk antibiotic prescriptions. The seizure-related, other neuropsychiatric disorders-related and all-cause hospitalization risks within 30 days after a high-risk antibiotic prescription in the three highest quartiles of antibiotic use in the past 6 months were compared to the lowest. The increased seizure risks associated with frequent high-risk antibiotic prescribing within 1-30 days are likely due to protopathic bias. In the sensitivity analyses, where the frequency of antibiotic exposure changed from 6 months to 1-year prior and the risks within 15-30 days were examined, no increase in seizure risks was observed. Frequent high-risk antibiotic prescribing did not incur a significantly higher risk of other neuropsychiatric disorders. A progressive increase in risks of all-cause hospitalization was observed with increased high-risk antibiotic prescribing. The findings suggest that clinicians should carefully balance the benefits of repeated antibiotic courses against potential risks when prescribing to people living with dementia.

Background:Peritonitis is a critical complication in patients undergoing peritoneal dialysis (PD). The association between gastric acid suppressants (GAS), specifically proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs), and peritonitis risk remains controversial, with conflicting evidence regarding their safety. Methods:We conducted a target trial emulation using Hong Kong electronic health records (2006-2019), applying a 168-month sequential design to minimize immortal time bias. Using inverse probability of treatment weighting and discrete hazards regression, we estimated hazard ratios (HRs) for peritonitis, all-cause mortality, and peritonitis-related mortality among PPI initiators, H2RA initiators, and non-initiators (95% confidence interval [CI] calculated using 500-resample bootstrapping). We also performed a PPI versus H2RA head-to-head comparison and predictive approaches to treatment effect heterogeneity analysis. Results:Among 11,693 individuals (240,431 person-trials), PPI initiation (vs. non-initiation) was associated with higher risks of peritonitis (HR 1.53, 95% CI 1.31-1.80), all-cause mortality (HR 1.55, 95% CI 1.43-1.67), and peritonitis-related mortality (HR 1.39, 95% CI 1.05-1.58). H2RA use was also associated with increased risk of peritonitis (HR 1.21, 95% CI 1.08-1.35) and all-cause mortality risks (HR 1.13, 95% CI 1.06-1.20). Head-to-head analysis showed no significant increase in peritonitis risk with PPIs versus H2RAs, but revealed an association between PPI use and higher all-cause mortality (HR 1.38, 95% CI 1.23-1.54) and peritonitis-related mortality (HR 1.85, 95% CI 1.07-3.19). Predictive approaches to treatment effect heterogeneity analysis indicated that risk elevations were more pronounced in individuals with higher baseline risk. Conclusions:In patients on PD, GAS initiation is associated with increased peritonitis and mortality compared with non-initiation. Furthermore, PPIs were associated with higher mortality risks than H2RAs. These findings highlight the need for cautious use of acid-suppressive therapy.

Introduction and Objective: American Diabetes Association (ADA) guidelines recommend early assessment of lipid levels in patients with diabetes mellitus (DM) and, in those at increased cardiovascular (CV) risk, initiation of lipid-lowering therapy (LLT) to reduce the risk of a first CV event and improve long-term outcomes. We examined lipid management patterns in patients with high-risk DM at risk for their first major atherosclerotic CV event in 11 databases from North America, Europe, and Asia-Pacific. Methods: Patients aged ≥ 50 years with coronary artery disease (CAD), atherosclerotic cerebrovascular disease (CeVD), or peripheral artery disease (PAD) or high-risk DM (defined as DM with microvascular complications or chronic insulin use) and elevated lipids and additional CV risk factors but no history of myocardial infarction or stroke were selected from de-identified claims or electronic medical records (2017-2022). The earliest date when all criteria were met was defined as the index. This analysis summarizes LLT use, LLT intensification, and low-density lipoprotein cholesterol (LDL-C) goal achievement based on local guidelines for the high-risk DM subgroup. Results: Out of 354,643 patients with high-risk DM (51% female), 14% also had CAD, atherosclerotic CeVD, or PAD. Fewer than half of the patients were on LLT at index (46%), and statin monotherapy was the predominant regimen (87%). For patients not on LLT at index, about 1 in 4 (26%) initiated LLT within 1 year post-index; for those who had ongoing LLT, 7% intensified their LLT within 1 year post-index. Around 42% of patients underwent LDL-C testing within 1 year of follow-up (n = 149,495), and 22% met their local guideline-recommended LDL-C goal. Conclusion: These findings show that globally, patients with high-risk DM are frequently untreated or undertreated, not having optimal lipid monitoring, and only a minority achieve ADA-recommended lipid management targets to lower the risk of major ischemic events. Disclosure Q. Chan: Employee; Current; Amgen Inc. S. Sakhuja: Employee; Current; Amgen Inc. M. Budoff: Speaker's Bureau; Current; Amgen Inc. Research Support; Current; Lilly. Speaker's Bureau; Current; Novo Nordisk A/S, Lilly. J. Cegla: Consultant; Current; Novartis Pharmaceuticals Corporation, Eli Lilly and Company, Amryt Pharma Plc, Amgen Inc., Daiichi Sankyo, Chiesi USA, Inc. J.H. Cornel: Advisory Panel; Current; Amgen Inc., Janssen Research & Development, LLC, Novo Nordisk, Sanofi. E. Hagstrom: Research Support; Ended; Pfizer Inc. Consultant; Current; Amgen Inc. Research Support; Current; Amgen Inc. Advisory Panel; Ended; Amarin Corporation. Research Support; Current; Novo Nordisk. Advisory Panel; Ended; Novo Nordisk. Speaker's Bureau; Ended; Sanofi. Other - National lead coin trial; Current; AstraZeneca. Advisory Panel; Ended; Bayer AG. G. Paiva da Silva Lima: Employee; Current; Amgen Inc. Stock/Shareholder; Current; Amgen Inc. M. Sibartie: Employee; Current; Amgen Inc. Stock/Shareholder; Current; Amgen Inc. I.C. Wong: Research Support; Current; Amgen Inc.

BackgroundAdherence to antihypertensive medication, alongside lifestyle modifications, is fundamental to managing hypertension and reducing the risk of cardiovascular disease. Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder associated with a range of cardiovascular diseases, including hypertension. ADHD medication has also been associated with hypertension. However, the influence of ADHD and ADHD medication on discontinuation and adherence to antihypertensive treatments is unknown.MethodsWe conducted a multinational cohort study using electronic health databases from seven countries, which included adults who initiated antihypertensive medication between 2010 and 2020. ADHD was identified by a diagnosis of ADHD or dispensation of ADHD medications. The outcomes were (1) time to the first discontinuation of antihypertensive medication and (2) poor adherence, defined as the proportion of days covered (PDC) below 80% during 1-, 2-, and 5-year follow-up periods. We used Cox proportional hazards models and logistic regression to estimate associations, adjusting for age, sex, and calendar year of antihypertensive medication initiation. We pooled results from different countries via random-effects meta-analysis.ResultsWe identified 12,174,321 adults who initiated antihypertensive medication during the study period, including 320,691 (2.6%) with ADHD. In the pooled analysis across all countries, ADHD was associated with an increased rate of discontinuation in 5-year follow-up of antihypertensive medication (hazard ratio [HR] 1.14; 95% CI, 1.02-1.27). In age-stratified analyses, ADHD was associated with a higher rate of antihypertensive medication discontinuation in middle-aged (HR, 1.11; 95% CI, 1.01-1.23) and older adults (HR, 1.14; 95% CI, 1.01-1.29), but not in young adults. Individuals with ADHD also had higher odds of poor adherence across 1 year after treatment initiation (odds ratio [OR] 1.45, 95% CI 1.26-1.67) to 5 years (OR 1.64, 95% CI 1.34-2.00). Among those with ADHD, use of ADHD medications was associated with lower odds of poor adherence (1 year OR 0.66, 95% CI 0.60-0.73; 5 years OR 0.58, 95% CI 0.46-0.72).ConclusionsAdults with ADHD are more likely to discontinue antihypertensive treatment and exhibit poor medication adherence. However, ADHD medication use appears to be associated with better adherence among individuals with ADHD.

BACKGROUND:Dihydropyridine calcium channel blockers have been implicated in both symptom improvement and exacerbation in pre-existing severe mental illness (SMI). We aimed to test the hypothesis that blood-brain barrier penetrant dihydropyridines (DHPs) reduce rates of mental health hospitalisation and self-harm compared to non-penetrant DHPs. METHODS:We used English electronic health records (Clinical Practice Research Datalink) to conduct a target trial emulation study in people with schizophrenia, bipolar disorder or other psychosis. We compared admissions for mental health and self-harm in those prescribed blood-brain barrier penetrant (intervention) and non-penetrant DHPs (control). Our primary endpoint was a 12-month intention-to-treat analysis using covariate adjustment. We additionally completed overlap weighting, per-protocol analyses and negative outcome controls. RESULTS:We included 918 people prescribed blood-brain barrier penetrant DHPs and 3384 prescribed amlodipine (control). In the primary covariate-adjusted intention-to-treat analysis, there was no clear evidence of a difference in rates of combined mental health admissions and self-harm events (adjusted hazard ratio (HR): 1.22; 95% confidence interval (CI): 0.78-1.91 at 12 months). In a pre-specified sensitivity analysis using overlap weighting, self-harm event rates were elevated in the intervention group at 12 months (HR: 2.10; 95% CI: 1.13-3.94); however, the equivalent covariate-adjusted estimate showed no clear difference (HR: 1.81; 95% CI: 0.52-6.26). CONCLUSION:In people with SMI, blood-brain barrier penetrant DHPs were not associated with reduced mental health hospitalisations or self-harm events compared to those treated with amlodipine, though estimates were imprecise. This active comparator design cannot distinguish between absence of effect or equivalent benefit of both drug classes. There are peripheral pathways through which DHPs may impact psychiatric symptoms and these require further exploration.

To investigate retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thickness in different attention-deficit/hyperactivity disorder (ADHD) subtypes and their association with ADHD symptom severity. This is a cross-sectional study included children aged 6–8 years in Hong Kong. ADHD diagnoses were made by psychiatrists based on ICD-10 criteria. Among 6431 children included in the study, 309 (4.80

CONTEXT:Vitamin D is implicated in cardiorespiratory fitness (CRF) through its roles in skeletal muscle metabolism and vascular function. Despite numerous studies linking vitamin D to CRF, no comprehensive meta-analysis has quantified their overall correlation or the effect of vitamin D interventions. OBJECTIVE:The objective of this review was to investigate any association between vitamin D concentration and CRF, and the effect of vitamin D supplementation on CRF. DATA SOURCES:PubMed, Embase, and Web of Science were systematically searched from their inception to November 2024. DATA EXTRACTION:A total of 20 observational studies (14 554 participants) and 9 interventional studies (733 participants) were included in the meta-analysis. DATA ANALYSIS:The effect size, correlation coefficient r, and a 95% CI (CI) were employed to estimate the correlation between vitamin D concentration and CRF. A random-effects model was used to calculate the standardized mean differences (SMDs) and 95% CIs. A significantly positive yet weak association (r = 0.17; 95% CI: 0.11, 0.24; P < .0001) was found between vitamin D concentration and CRF, with high heterogeneity (I2 = 88.0%, P heterogeneity < .0001). The correlation coefficient in children (r = 0.05; 95% CI: 0.01, 0.09; P = .0273) was smaller than that in adults (r = 0.26; 95% CI: 0.17, 0.34; P < .0001) (Psubgroup < .0001). No significant differences were observed between study subgroups stratified by gender, CRF measurement method, vitamin D assays, or physical activity level (all Psubgroup > .05). Interventional studies revealed that the effect of vitamin D supplementation on CRF is not significant (SMD: 0.03; 95% CI: -0.12, 0.17; P = .8959), with 0% heterogeneity. CONCLUSION:This meta-analysis confirms there is a small but significant positive relationship between vitamin D concentrations and CRF, especially in adults. However, the studies found no improvement in CRF through vitamin D supplementation in interventional trials. SYSTEMATIC REVIEW REGISTRATION:PROSPERO registration No. CRD42024574603.

Previous evidence suggests a potential protective effect of warfarin against cancer, compared to non-users. However, it may be prone to immortal time bias and residual confounding. We aimed to examine the association between cancer and warfarin, compared with active comparator (direct oral anticoagulants). We conducted studies using population-based databases from England and Hong Kong to investigate the association between warfarin and hazard of cancer using a new-user active-comparator cohort design. People with atrial fibrillation aged ≥ 18 years who had first received anticoagulant treatment during 01/01/2011–31/12/2019 were involved. No evidence supported the association between warfarin and hazard of overall cancer, compared with direct oral anticoagulants in both settings (England: hazard ratio [HR] = 1.03, 95

Importance:Child maltreatment is a major global public health concern with well-documented psychological consequences, but its associations with long-term physical health conditions remain less well understood. Objective:To examine the associations between childhood maltreatment and adult multimorbidity using electronic health records in Hong Kong. Design, Setting, and Participants:This population-based cohort study used electronic health record data from Hong Kong, comprising 7473 individuals with a first recorded episode of maltreatment between ages 0 and 19 years from 2001 to 2010 and 26 834 matched individuals without documented maltreatment. Individuals who reached adulthood (ie, after age 19 years) by December 31, 2024, were included. Exposure:History of childhood maltreatment vs none. Main Outcomes and Measures:The primary outcome was the occurrence of multimorbidity during adulthood as documented in participants' diagnostic records through December 31, 2024. Cox proportional hazards models were used to estimate the risks of 16 disease categories and multimorbidity patterns diagnosed after age 19 years, both overall and stratified by preexisting physical, mental, or neurodevelopmental conditions in childhood. Results:After exclusions, the final cohort comprised 32 674 individuals (16 986 female [52%]), including 7137 who were exposed to childhood maltreatment and 25 537 unexposed individuals. Their median (IQR) age was 9.0 (6.0-13.0) years at inclusion and 28.1 (24.2-31.6) years at the end of follow-up. The median (IQR) follow-up duration was 19.0 (16.6-21.3) years. Childhood maltreatment was associated with increased risks across 13 adult diagnostic categories. The highest risks were observed with mental and behavioral disorders (hazard ratio [HR], 2.78; 95% CI, 2.49-3.09), ear diseases (HR, 1.88; 95% CI, 1.27-2.78), injuries (HR, 1.81; 95% CI, 1.65-1.98), and blood diseases (HR, 1.67; 95% CI, 1.41-1.97). Maltreatment was also associated with a higher risk and earlier onset of complex multimorbidity (HR, 1.96; 95% CI, 1.68-2.27). The associations between childhood maltreatment and adult diagnoses were attenuated among individuals with mental health or neurodevelopmental conditions diagnosed in childhood. Conclusions and Relevance:In this 19-year cohort study of 32 674 individuals, childhood maltreatment was associated with elevated risks for multiple health conditions in adulthood. These findings underscore the need for early prevention and sustained, trauma-informed health care support to reduce the risk of lifelong multimorbidity among children who have experienced maltreatment.

BACKGROUND:Bleeding is a side effect of direct oral anticoagulants (DOACs) and selective serotonin reuptake inhibitors (SSRIs). However, it is unknown whether their concomitant use would further exacerbate bleeding risk. AIM:To compare hazard of bleeding in patients with concomitant use of DOACs and SSRIs versus non-SSRI antidepressants. DESIGN & SETTING:Population-based cohort and case-crossover study using primary care data from the UK Clinical Practice Research Datalink (CPRD) Aurum between 1/1/2011 and 29/3/2021. METHOD:We used a cohort design to estimate hazard ratios (HRs) using propensity score weighting, comparing DOAC+SSRI and DOAC+non-SSRI users, and a 6-parameter model case-crossover design comparing odds of exposure to different drug initiation patterns for outcomes in hazard vs referent window within an individual to eliminate time-invariant confounding (confounding that do not change over time). RESULTS:There was no difference in bleeding risk in the cohort design (intracranial bleeding: HR1.16, 99% confidence interval [CI] 0.62-2.20; gastrointestinal bleeding: HR1.09, 99% CI 0.83-1.41; other bleeding: HR1.01, 99% CI 0.78-1.29). In the case-crossover design, we observed higher odds ratio (OR) of 1.64 (99%CI 1.14-2.35) for other bleeding associated with SSRI initiation while taking DOAC than SSRI monotherapy (OR1.06; 99% CI 1.01-1.11; p for Wald test=0.002), but greater odds ratio was not observed in DOAC users initiated non-SSRI (p for Wald test=0.83). CONCLUSION:We found no evidence of increased risk of intracranial and gastrointestinal bleeding during concomitant use of DOAC+SSRI in the cohort analysis. However, the case-crossover analysis suggested some evidence of a higher risk of other bleeding when initiating SSRIs (but not non-SSRIs) while taking DOACs.

BackgroundConsumption of gabapentinoids has increased worldwide in recent years, and the association between its use and drug poisoning is of public health concern. This study aimed to investigate the association between gabapentinoid treatment and the risk of drug poisoning.Methods and findingsIn this within-individual study, we utilised data from the United Kingdom (UK) Clinical Practice Research Datalink (CPRD) Aurum database linked to the Hospital Episode Statistics (HES) and Office for National Statistics (ONS). The analysis included individuals aged 18 or above who were prescribed gabapentinoids and had an incident all-cause drug poisoning event between 1st January 2010 and 31st December 2020. Using the self-controlled case series (SCCS) design, we assessed the risk of drug poisoning incidence in predefined risk periods: 90 days before treatment initiation, first 28, 29-56, 57-84 days, and the remaining treatment time. Concomitant use with opioids/benzodiazepines was also evaluated. Adjusted incidence rate ratios (aIRRs) were calculated using conditional Poisson regression. A case-case-time-control (CCTC) analysis was also conducted, with adjusted odds ratio (aOR) calculated to validate the findings from the main SCCS analysis. All analyses have adjusted for key time-varying confounders, including age, season, and concomitant use of opioids, antiseizure medications, psychotropic medications, and non-steroidal anti-inflammatory drugs (NSAIDs). 16,827 individuals met the inclusion criteria and were included in the SCCS analysis. The risk of drug poisoning, compared with the reference periods, increased during the first 28 days of gabapentinoid treatment (aIRR = 1.81, 95% confidence interval [CI] [1.66, 1.99]; p < 0.001), eventually dropped to 1.11 (95% CI [1.05, 1.17]; p < 0.001) in the remainder of the treatment period. Notably, the risk was doubled during the 90-day preceding treatment initiation (aIRR = 2.09, 95% CI [1.98, 2.21]; p < 0.001). Co-administration with opioids elevated the risk by 30%, while benzodiazepines increased it 2-fold. The CCTC analysis also detected an increased aOR of 1.36 (95% CI [1.12, 1.65]; p = 0.002) of receiving gabapentinoid treatment within 30 days prior to a drug poisoning event. The SCCS approach cannot completely exclude the effect of unmeasured time-varying confounders, such as transient changes in socioeconomic status, major life events, or illicit drug use, although the negative control analysis did not suggest meaningful residual confounding.ConclusionsThe results suggest that gabapentinoid is associated with an increased risk of drug poisoning. Close monitoring throughout gabapentinoid treatment journey for drug poisoning is needed, especially at the initial phase. Concomitant use with opioid or benzodiazepines should be avoided.

BACKGROUND:Statins, renin-angiotensin system inhibitors (RASIs) and beta-blockers are guideline-recommended cardiovascular medications post-myocardial infarction (MI) for secondary prevention, but evidence for people with dementia is scarce. OBJECTIVE:To evaluate the association between post-MI cardiovascular medication use and the risk of cardiovascular outcomes and mortality, focusing on people with dementia. DESIGN:Large retrospective cohort study using data from Australia, Finland, Taiwan, the UK and the USA. SUBJECTS:People with and without dementia. METHODS:Seven exposure groups were assigned using one or combinations of the three guideline-recommended medication classes-(i) statin, RASI and beta-blocker, (ii) statin and beta-blocker, (iii) statin and RASI, (iv) RASI and beta-blocker, (v) statin only, (vi) beta-blocker only and (vii) RASI only, based on medication records during a 60-day landmark period post-MI. Recurrent MI, major adverse cardiovascular event (MACE) and all-cause mortality were evaluated as outcomes. Jurisdiction-specific results were pooled together using meta-analyses. RESULTS:A total of 28 122 people with dementia and 260 360 people without dementia were included. Among people with dementia, using any single or two medications carried a similar risk of recurrent MI and MACE as using all three guideline-recommended medications, except that using RASI and a beta-blocker without a statin was associated with a lower risk of recurrent MI (HR 0.85; 95% CI, 0.75-0.96). Using a statin and RASI without beta-blockers resulted in similar all-cause mortality to using all three (HR 1.16; 95% CI, 0.97-1.39), while all the remaining single- or dual-medication regimens were associated with higher risks of all-cause mortality. CONCLUSIONS:For people with dementia, using one or two guideline-recommended medications appeared sufficient to protect against recurrent MI and MACE. Beta-blockers may not provide additional survival benefits over statins and RASIs.

BACKGROUND:Early discontinuation of attention-deficit/hyperactivity disorder (ADHD) medication is common and linked to worse outcomes. Identifying clinical predictors could aid personalised treatment yet evidence is inconsistent across ages and countries/regions. OBJECTIVE:Investigate psychiatric and neurological comorbidity as predictors of early ADHD medication discontinuation in new ADHD medication users across age groups, sex and countries/regions. METHODS:Using health records from eight countries/regions, we identified 1 000 411 (44% female) new ADHD medication users (2011-2020). Discontinuation was defined as a ≥180 day gap between dispensations. We examined 23 indicators of psychiatric or neurological comorbidity, severity and psychotropic medication use. Associations were estimated using Cox regression, pooled with random-effects meta-analyses and stratified by age-at-initiation and sex. FINDINGS:Discontinuation rates varied widely (children 19%-61%, adolescents 37%-68%, young adults 52-67%, adults 38%-68%). In pooled analyses, earlier discontinuation in children was predicted by intellectual disability, autism and use of psychotropic medications (HR range 1.32-1.51), while conduct/oppositional defiant disorder (CD/ODD) was protective (HR 0.83, 95% CI 0.73 to 0.94). In adolescents, no indicators remained statistically significant after multiple-testing control. In young adults, CD/ODD (HR 1.42, 95% CI 1.30 to 1.55), and in adults, schizophrenia (HR 1.25, 95% CI 1.09 to 1.44) and tic disorders (HR 1.27, 95% CI 1.11 to 1.46) predicted earlier discontinuation. Statistical heterogeneity was substantial, largely driven by US estimates. In meta-analyses excluding the USA, additional associations emerged. For example, in children, OCD and anxiety disorders predicted earlier discontinuation, while eating disorders and antidepressants/anxiolytics were protective in adults. Associations with schizophrenia, tic disorders and CD/ODD were no longer significant. Country-specific analyses showed similar association patterns, except in the USA, Hong Kong and the UK. Sex differences were limited. CONCLUSIONS:Children with neuropsychiatric comorbidity and related comedication are more likely to discontinue ADHD medication early, whereas few consistent predictors were seen from adolescence onwards. Marked cross-country variation, particularly in the USA, points to system-level influences on treatment patterns. CLINICAL IMPLICATIONS:Improving ADHD medication persistence will require consideration of healthcare context and age-specific strategies, including close monitoring for children with complex neuropsychiatric profiles, and consideration of broader factors in adolescents and adults, where clinical predictors were limited.

BACKGROUND:Gabapentinoids are increasingly being prescribed in older adults (aged 60 years or older), but concerns have been raised that their adverse effects on the CNS can increase the risk of fractures. Previous studies have reported associations between gabapentinoid use and fracture, but many have not adequately addressed confounding by indication or examined risk across the treatment journey. Therefore, we aimed to investigate the temporal association between gabapentinoid treatment and fracture in older adults, and to assess whether concomitant opioid or benzodiazepine use further modifies this risk. METHODS:In this retrospective multinational population-based study, we used data from the UK Clinical Practice Research Datalink (CPRD) Aurum database and the South Korea National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). The analysis included individuals aged 60 years or older prescribed a gabapentinoid and who had a hospitalised fracture between Jan 1, 2010, and Dec 31, 2020, in the UK and between Jan 1, 2003, and Dec 31, 2019, in South Korea. The observation period for each included individual was divided into four mutually exclusive windows: 90 days before gabapentinoid treatment (pre-exposure window), first 60 days of treatment period (focal window 1), remaining time of the treatment period (focal window 2), and all other non-treatment periods (referent window), to capture how risk varied across the treatment course. Adjusted incidence rate ratios (aIRRs) with 95% CI of fracture during different risk windows were estimated using conditional Poisson models within each country, and the country-specific aIRRs for the same risk window were then pooled using a random-effects model. FINDINGS:We included 20 030 participants in CPRD and 2935 in NHIS-HEALS in the analysis. In the CPRD cohort, 15 366 (76·7%) were women and the mean age at event was 77·85 years. In the NHIS-HEALS cohort, 2007 (68·4%) were women and the mean age at event was 69·24 years. The pooled results showed an increased risk of fracture during the pre-exposure window (aIRR 2·92, 95% CI 1·61-5·28, p=0·0004). The aIRR was 1·31 (95% CI 1·00-1·71, p=0·051) in the first 60 days of the treatment period and did not increase for the remainder of the treatment period (0·84, 0·54-1·32, p=0·45). Concurrent prescription of opioids or benzodiazepines elevated the risk of fracture, with an aIRR of 3·15 (95% CI 2·85-3·48, p<0·0001) for opioids and 1·91 (1·50-2·44, p<0·0001) for benzodiazepines during the first 60 days of gabapentinoid treatment period. INTERPRETATION:The risk of fracture was the highest in the period before the commencement of gabapentinoid treatment and declined after initiation of treatment. The results do not support a sustained causal relationship between gabapentinoid use and risk of fracture in older adults but warrant fall and fracture-prevention measures around gabapentinoid initiation. The elevated fracture risk observed with concomitant opioid or benzodiazepine use highlights the need for careful review of concurrent sedating medicines when initiating gabapentinoids. FUNDING:UK National Institute for Health and Care Research; Hong Kong Innovation and Technology Commission; Ministry of Food and Drug Safety, South Korea.

Real-world evidence on lipid-lowering therapy (LLT) use and low-density lipoprotein cholesterol (LDL-C) control in patients at high cardiovascular (CV) risk without prior myocardial infarction (MI) or stroke remains limited. We evaluated LLT use, treatment intensification, LDL-C monitoring, and LDL-C goal attainment across North America, Europe, and Asia-Pacific. VESALIUS-REAL is a retrospective observational study using a common protocol across 11 databases between 2017 and 2022. Eligible patients (aged ≥ 50 years) had coronary artery disease, atherosclerotic cerebrovascular disease, peripheral artery disease, or high-risk diabetes, together with elevated lipids, and additional CV risk factors, but no history of MI or stroke or end-stage renal disease. The earliest date when all criteria were met was defined as the index date. LLT patterns and local guideline-recommended LDL-C goal achievement were summarised. Among 1,126,756 patients (51

KEY POINTS:Statin initiation in adults with normal kidney function lowered risks of mortality and major adverse kidney events. Statins yielded modest yet clinically meaningful absolute risk reductions for mortality and GFR declines. The observed pleiotropic benefits justified using statins for simultaneous cardiovascular risk reduction and kidney protection. BACKGROUND:Evidence on the kidney-protective effects of statins in individuals with normal kidney function is mixed, with some trials suggesting benefits and others raising concerns about AKI. This study evaluates the effect of statin initiation on kidney function in adults with normal kidney function. METHODS:Sequential target trial emulation on the basis of electronic health records in the Hong Kong Hospital Authority were conducted. Patients aged 18 year or older with normal kidney function (eGFR ≥60 ml/min per 1.73 m 2 ) who met the indication for statin therapy ( i.e ., LDL-cholesterol ≥100 mg/dl without cardiovascular disease or ≥70 mg/dl with cardiovascular diseases) in Hong Kong between January 2008 and December 2017 were included. Statin initiators and noninitiators were matched using 1:1 propensity score matching. Hazard ratio (HR) and 10-year absolute risk reduction (ARR) of outcomes, including impaired kidney function (eGFR <15 and <60 ml/min per 1.73 m 2 ), kidney function deterioration (≥30% and ≥50% eGFR decline), and all-cause mortality, were estimated using weighted pooled logistic regression on intention-to-treat approach. RESULTS:Among 449,595 statin initiators and 449,595 matched noninitiators, statin use was associated with a lower risk of eGFR <15 ml/min per 1.73 m 2 (HR, 0.92 [0.90 to 0.95]; ARR, -0.33% [-0.42% to -0.24%]), eGFR <60 ml/min per 1.73 m 2 (HR, 0.97 [0.96 to 0.98]; ARR, -0.98% [-1.12% to -0.84%]), ≥30% eGFR decline (HR, 0.94 [0.93 to 0.95]; ARR, -1.81% [-2.00% to -1.60%]), ≥50% eGFR decline (HR, 0.90 [0.88 to 0.91]; ARR, -0.98% [-1.11% to -0.85%]), and all-cause mortality (HR [95% confidence interval], 0.90 [0.89 to 0.91]; ARR [95% confidence interval], -1.63% [-1.76% to -1.49%]). CONCLUSIONS:Statin initiation in adults with normal kidney function was associated with modestly lower all-cause mortality and kidney function impairment, supporting a potential kidney protective benefit of statins without increasing the risks of adverse kidney outcomes.

BACKGROUND:Antipsychotics are the cornerstone of schizophrenia management, with antipsychotic polypharmacy commonly observed. This study aims to evaluate the trends of antipsychotic use and polypharmacy among individuals with schizophrenia in Hong Kong. METHODS:This retrospective study used territory-wide electronic health records to identify all individuals aged ≥18 years diagnosed with schizophrenia in Hong Kong (2004-2024). Annual prevalence rates of antipsychotics and polypharmacy were calculated, with trend analysis using Joinpoint regression. FINDINGS:The overall use of antipsychotics remained stable, with a slight decrease during the study period (average annual percentage change [AAPC] -0.40 [95% CI, -0.42 to -0.38]), though individual agents shifted substantially. There were opposing trends with a crossover from first to second-generation antipsychotics (SGA) predominance, while a less pronounced increase in SGA over the past decade. In 2024, olanzapine emerged as the most prevalent antipsychotic (20.6%), while clozapine utilisation grew but remained relatively limited (7.5%). Use of long-acting injectable antipsychotics (LAIA) declined (AAPC = -0.92 [-1.07 to -0.77]), except SGA-LAIA, which rose, primarily driven by LAIA-paliperidone and LAIA-aripiprazole. Antipsychotic polypharmacy prevalence decreased initially from 24.0% in 2004 to 22.4% in 2011, then increased to 28.0% in 2024 (AAPC = 0.74 [0.62 to 0.90]). In 2024, the most common combinations were oral aripiprazole and oral olanzapine (5.68%), oral amisulpride and oral olanzapine (4.22%), and LAIA-paliperidone and oral olanzapine (4.05%). CONCLUSION:Over the last two decades, overall antipsychotic use in schizophrenia remained stable in Hong Kong, though patterns shifted between agents. Antipsychotic polypharmacy became more prevalent, emphasising the need for further research on their safety and effectiveness.

Context Bone metabolism interplays with liver metabolism, also known as the liver-bone axis. Osteoporosis is a common complication of cirrhosis, but whether bone mineral density (BMD) can predict cirrhosis development is unknown.Objective This study aims to investigate the relationship between BMD and the risk of incident cirrhosis in the Hong Kong Osteoporosis Study (HKOS).Methods BMD was measured at the lumbar spine, femoral neck, total hip, and trochanter of 7752 participants by dual-energy x-ray absorptiometry (DXA), and the incidence of cirrhosis and mortality were followed by linking to the territory-wide electronic health records database. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CI.Results With a median follow-up of 18.43 years, 42 incident cirrhosis were identified. Higher BMD T-scores at the femoral neck, total hip, and trochanter were significantly associated with a reduced risk of cirrhosis (femoral neck: HR 0.56; 95% CI, 0.39-0.82; total hip: HR 0.60; 95% CI, 0.44-0.82; trochanter: HR 0.63; 95% CI, 0.46-0.88). Similar associations were observed in participants without risk factors of cirrhosis at the baseline and further adjusting for the baseline level of alkaline phosphatase, albumin, and alanine transaminase. Consistent relationships in multiple sensitivity analyses suggest the robustness of the results.Conclusion Low BMD could be a novel risk factor and early predictor for cirrhosis, with consistent associations observed in multiple sensitivity analyses.