Background: Low-dose aspirin is recommended to prevent preeclampsia in pregnancies at high risk. It modulates the maternal immune system through COX-1 inhibition, raising concerns about potential risks of atopic triad and neurodevelopmental disorders in offspring. However, existing evidence on these risks remains conflicting.
Objectives: To evaluate the association of aspirin and the risks of atopic triad and neurodevelopmental disorders among pregnancies at high risk of preeclampsia
Methods: We emulated a sequence of 29 target trials of aspirin use between 0 and 28 weeks of gestation, using Taiwan's National Health Insurance Research Database from 2011 to 2021. In each sequential trial, pregnancies at high risk of preeclampsia without prior use of aspirin were eligible. Treatment strategies were aspirin use versus no-use at each gestational week. We used propensity score with IPTW to emulate randomization in the target trial. The primary outcomes were atopic triad (including atopic dermatitis, asthma, and allergic rhinitis) and neurodevelopmental disorders. The follow-up began with treatment assignment and ended at the occurrence of outcomes, delivery, or end of study period. The causal contrast of interest was intention-to-treat. We used pooled log-binomial regression models to estimate relative risk (RR) across the 29 sequential trials. We performed subgroup analyses stratified by pregnancy trimesters to assess the effect of aspirin during different biological windows.
Results: Among 58,178 pregnancies initiating aspirin and 684,245 not initiating, the mean age was 32.9 years (SD, 5.1) and 31.5 years (SD, 5.0), respectively. After propensity score weighting, we observed no association between aspirin use and the risks of atopic triad (RR: 0.97; 95% CI: 0.89-1.05) and neurodevelopmental disorders (RR: 1.02; 95% CI: 0.95-1.09). Results from different trimesters yielded consistent results to the main analyses.
Conclusion: Low-dose aspirin use during pregnancy was not associated with an increased risk of atopic triad or neurodevelopmental disorders in offspring.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents. Despite rising global use of pharmacological treatments and growing concerns in South Korea over the potential misuse of ADHD medications as “smart drugs,” comprehensive population-based utilization studies remain scarce.

Aims: To examine national trends in methylphenidate and atomoxetine use among South Korean children and adolescents using defined daily dose (DDD)-based drug utilization metrics.

Methods: This cross-sectional study used the Health Insurance Review and Assessment Service Pediatric Patient Sample database, which included patients aged 3–19 years who were prescribed methylphenidate or atomoxetine between 2010 and 2018. Medication use was assessed using cumulative DDD and standardized DDD per 1,000 patients per day. Analyses were stratified by sex, age group [preschool children (3-5 years), children (6-12 years), adolescents (13-19 years)], and geographic region [Seoul, capital region (Incheon and Gyeonggi), other metropolitan cities, and rural areas]. Monthly and annual trends were evaluated.

Results: Between 2010 and 2018, both cumulative DDD and standardized DDDs for ADHD medications increased steadily. Methylphenidate remained the predominant medication prescribed, comprising 83.2%, while atomoxetine demonstrated a consistent upward trend, increasing from 14.9% to 17.6%. ADHD medication use was significantly higher among boys, with most prescriptions in the 6–12 years (64.7%), followed by 13–15 years (22.8%), underscoring the predominance of school-aged children in the treatment population. Seoul exhibited higher standardized DDDs for methylphenidate and atomoxetine (1,474 and 626, respectively) compared to rural areas (1,244 and 553), suggesting significant regional disparities in treatment access. Monthly prescription patterns exhibited cyclical fluctuations, with distinct peaks during school semesters and declines during school vacations.

Conclusion: ADHD medication use among South Korean youth showed notable disparities by region, age group, and seasonal variation. These patterns highlight the need for continuous monitoring, as well as individual and region-specific strategies, to ensure appropriate ADHD treatment.

Introduction:
Surgery and trauma can lead to persistent opioid use (POU), characterised by continuous opioid consumption following hospital discharge. Outside the United States, there is a lack of population-based studies on POU outcomes in opioid-naive patients following these events.
Aims:
To evaluate the impact of POU following surgery or trauma on health outcomes using linked data.
Methods:
We included opioid-naïve patients who were dispensed opioids after being discharged following admission for surgery or trauma to any New Zealand (NZ) hospital from 2007 to 2019. Differences in outcomes between individuals with and without POU were assessed between 180 and 360 days after discharge. The primary outcome was all-cause mortality; the secondary outcomes were all-cause and opioid-related hospitalisation, and Days Alive and Out of Hospital (DAOH). Cox and quantile multivariable regression models were used to examine the association between POU and outcomes.
Results:
Overall, 298,928 surgical and 206,663 trauma patients were included in the final analyses, and 17,779 (5.9%) surgical and 17,867 (8.6%) trauma patients developed POU. POU was significantly associated with increased risk of all-cause mortality (surgical, aHR=6.59; 95% CI: 5.82–7.46; trauma, aHR=2.77; 95% CI: 2.47–3.11), all-cause hospitalization (surgical, aHR=2.02; 95% CI: 1.95–2.08; trauma, aHR=1.57; 95% CI: 1.52–1.62), opioid-related hospitalization (surgical, aHR= 2.49; 95% CI: 2.24–2.76; trauma, aHR=1.89; 95% CI: 1.73–2.05) and reduced DAOH.
Conclusion:
Among opioid-naive patients who received opioids after surgery or trauma, POU was associated with worse outcomes, including increased mortality. Further investigation is warranted to understand the reasons for continued opioid use beyond 90 days and the mechanisms associated with harm.

Keywords: opioid, persistent opioid use, surgery, trauma

Introduction
Gabapentinoids are known to impair coordination. However, it remains uncertain whether they elevate the risk of traumatic fractures in older adults, or if this risk varies across different healthcare settings.

Aims
To investigate the association between gabapentinoid and risk of traumatic fractures among older adults in the United Kingdom and South Korea.

Methods
We performed a multinational self-controlled case series study using data from the UK Clinical Practice Research Datalink (CPRD) Aurum (linked to Hospital Episode Statistics and Office for National Statistics) and South Korea National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). Adults aged ≥60 prescribed gabapentinoids with an incident traumatic fracture were included. Four mutually exclusive risk windows were defined: 90-day pre-treatment, first 60 days of treatment period, remaining time of treatment period, and non-treatment reference period. Adjusted incidence rate ratios (aIRRs) and 95% CIs were estimated using conditional Poisson models with age, season and concomitant medications addressed as time-varying factors , and country-specific results were pooled using random effects model.

Results
20,030 in CPRD Aurum (15,366 female [76.71%]; mean [SD] age at event, 77.85 [9.07] years) and 2,935 in NHIS-HEALS (2,007 female [68.38%]; mean [SD] age at event, 69.24 [5.73] years) were included in the analysis. The pooled results showed an increased risk of traumatic fracture during the pre-treatment period (aIRR, 2.92; 95% CI, 1.61–5.28). It then decreased to 1.31 (95% CI, 1.00–1.71) in the first 60 days of the treatment period, and further subsided in the remainder of treatment period (aIRR, 0.84; 95% CI, 0.54–1.32). Results were consistent across subgroups and sensitivity analyses.

Conclusions
Traumatic fracture risk peaked before gabapentinoid initiation and declined to non-treatment reference level during the rest of treatment period. The findings do not support a causal relationship but warrant fall and fracture prevention measures, particularly at gabapentinoid initiation.

Introduction:
Switching to prolactin (PRL)-sparing antipsychotics is a common strategy to reduce elevated prolactin levels for PRL-increasing antipsychotic users. Aripiprazole can effectively lower serum prolactin levels, but whether this reduces related adverse outcomes remains unclear.
Aims:
This study evaluated whether switching to aripiprazole, compared to other PRL-sparing antipsychotics, reduces fracture risk as a clinically relevant adverse outcome associated with elevated prolactin levels.
Methods:
We conducted a matched cohort study using the Hong Kong Hospital Authority electronic health record database. Patients aged 18–85 who used PRL-increasing antipsychotics between 2006–2020 and switched to PRL-sparing antipsychotics were included. The index date was the first switch date. 1:2 probability density sampling was used to match aripiprazole users with users of other PRL-sparing agents by sex, age, and prior follow-up duration (within 30 days). We excluded individuals with prior cancer (excluding non-melanoma skin cancer), fractures, or diabetes. Follow-up was from the index date until fractures, 365 days after discontinuation or switching of antipsychotics, the end of study (December 31, 2023), 3 years of follow-up, or death. Cox models weighted by inverse probability of treatment estimated hazard ratios (HRs) for all fractures and subtypes.
Results:
Among 9,719 patients (mean age 37.7 years, 69.7% female), 3,715 aripiprazole users were matched to 6,004 other PRL-sparing users. Median follow-up was 1.09 years. Aripiprazole users had a lower risk of all-type fractures (HR: 0.45, 95% CI: 0.26–0.77, p=0.003). The HR was 0.43 (0.20–0.92) for full switchers and 0.47 (0.22–1.03) for those continuing PRL-increasing agents. Reductions were significant for spine/trunk (0.14 [0.03–0.58], 0.007) and lower limb fractures (0.50 [0.25–0.98], 0.045).
Conclusions:
Switching to aripiprazole was associated with a lower fracture risk among prior PRL-increasing antipsychotic users, suggesting potential to reduce high prolactin-related adverse outcomes.

Introduction: Major depressive disorder (MDD) imposes a substantial burden on global health systems, negatively impacting quality of life, cognitive function, and workplace productivity. Antidepressants are the mainstay of pharmacologic treatment, yet their cost-effectiveness varies considerably. In China, comprehensive economic evaluations comparing antidepressants remain scarce.
Objectives: To evaluate the cost-effectiveness of 16 commonly used antidepressants for MDD treatment in China and to develop a meta-model that enhances modeling efficiency and interpretability.
Methods: A decision-analytic model was constructed to simulate MDD treatment outcomes over a two-year horizon from the Chinese healthcare system perspective. The model incorporated clinical efficacy, adverse event profiles, drug costs, and utility values, drawing from published meta-analyses, health technology assessments, and national procurement data. Key outcomes included total cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). A meta-model was built using linear regression and generalized additive models (GAMs) to characterize the relationships between inputs and outcomes. Model performance was evaluated using R² and root mean square error (RMSE).
Results: In the base-case analysis, agomelatine emerged as the most cost-effective option, with an ICER of CNY 79,711.10 per QALY—well below China’s 2023 per capita GDP threshold. Drug cost was the primary driver of uncertainty; agomelatine’s price had a significant impact on its ICER. Probabilistic sensitivity analysis indicated that agomelatine had the highest probability of being cost-effective at WTP thresholds up to three times the per capita GDP. The meta-models demonstrated strong predictive performance (R² = 0.97–0.99); the linear model was more accurate for cost prediction, while the GAM showed slightly better performance for QALY estimation.
Conclusions: Agomelatine offers a cost-effective option for MDD treatment within the Chinese healthcare system. The use of meta-modeling enhances transparency and interpretability in cost-effectiveness analyses, supporting more efficient and evidence-based decision-making in mental health policy.
Keywords: Cost-Effectiveness Analysis, Antidepressants, Meta-Modeling