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Introduction: The use of benzodiazepines and/or z-drugs in women of childbearing age has increased. Objective: The aim of the study was to evaluate whether gestational benzodiazepine and/or z-drug exposure is associated with adverse birth and neurodevelopmental outcomes. Methods: A population-based cohort including mother-child pairs from 2001 to 2018 in Hong Kong was analysed to compare gestationally exposed and nonexposed children on the risk of preterm birth, small for gestational age, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) through logistic/Cox proportional hazards regression with a 95% confidence interval (CI). Sibling-matched analyses and negative control analyses were applied. Results: When comparing gestationally exposed with gestationally nonexposed children, the weighted odds ratio (wOR) was 1.10 (95% CI = 0.97–1.25) for preterm birth and 1.03 (95% CI = 0.76–1.39) for small for gestational age, while the weighted hazard ratio (wHR) was 1.40 (95% CI = 1.13–1.73) for ASD and 1.15 (95% CI = 0.94–1.40) for ADHD. Sibling-matched analyses showed no association between gestationally exposed children and their gestationally nonexposed siblings for all outcomes (preterm birth: wOR = 0.84, 95% CI = 0.66–1.06; small for gestational age: wOR = 1.02, 95% CI = 0.50–2.09; ASD: wHR = 1.10, 95% CI = 0.70–1.72; ADHD: wHR = 1.04, 95% CI = 0.57–1.90). Similarly, no significant differences were observed when comparing children whose mothers took benzodiazepines and/or z-drugs during pregnancy to children whose mothers took benzodiazepines and/or z-drugs before but not during pregnancy for all outcomes. Conclusions: The findings do not support a causal relationship between gestational benzodiazepines and/or z-drugs exposure and preterm birth, small for gestational age, ASD, or ADHD. Clinicians and pregnant women should carefully balance the known risks of benzodiazepines and/or z-drugs use against those of untreated anxiety and sleep problems.

New antidiabetic agents (sodium-glucose cotransporter-2 inhibitor [SGLT2i] and glucagon-like peptide-1 receptor agonist [GLP-1RA]) and metabolic surgery have protective effects on metabolic syndromes.To compare the changes of metabolic parameters and costs among patients with obesity and type 2 diabetes undergoing metabolic surgery and initiating new antidiabetic agents over 12 months.Hong Kong Hospital Authority database from 2006-2017.This is a population-wide retrospective cohort study consisting of 2616 patients (1810 SGLT2i, 528 GLP-1RA, 278 metabolic surgery). Inverse probability treatment weighting of propensity score was applied to balance baseline covariates of patients with obesity and type 2 diabetes who underwent metabolic surgery, or initiated SGLT2i or GLP-1RA. Metabolic parameters and direct medical costs were measured and compared from baseline to 12 months in metabolic surgery, SGLT2i, and GLP-1RA groups.Patients in all 3 groups had improved metabolic parameters over a 12-month period. Patients with metabolic surgery achieved significantly better outcomes in BMI (-5.39, -.56, -.40 kg/mBeneficial weight loss and metabolic outcomes at 12 months were observed in all 3 groups, among which the metabolic surgery group showed the most remarkable effects but incurred the greatest medical costs. However, studies with a longer follow-up period are warranted to show long-term outcomes.

In spite of the preliminary evidence suggesting a link between gestational use of antidepressant and neurodevelopmental disorders in their offspring, the association between maternal use of antidepressants during pregnancy and the risk of neurologically-related adverse outcomes such as neonatal seizure is still unclear. This study summarises the available evidence on the association between gestational exposure to any antidepressants and the risk of seizure in neonates and children. We found that gestational antidepressant exposure is associated with a 2.3-fold higher incidence of seizure in offspring. Although a causal relationship cannot be confirmed in view of other potential confounders, our findings warrant future research on related clinical aspects, and possibly more careful monitoring of foetal neurodevelopment in pregnant women taking antidepressants during pregnancy. However, this does not suggest the abrupt withdrawal of antidepressants during pregnancy for all cases at risk of seizure in offspring as this must be balanced with the risk of negative consequences caused by untreated maternal depression, and decision-making should be individualised for each patient.

There are many case reports of seizures apparently associated with the prescription of antipsychotics. This study aimed to examine whether there is an association between the prescription of antipsychotics and incident seizures in individuals with autism spectrum disorder using retrospective data based on patients’ chart review. A cohort study was conducted to compare the rate of incident seizure between 3923 users of antipsychotics with 10,086 users of other psychotropics. This was followed by a self-controlled case series (SCCS) analysis of 149 patients to eliminate the effect of time-invariant confounders. The results showed no evidence of increased risk of seizure after exposure to antipsychotic agents (Hazard Ratio 1.28, 95% CI 0.74–2.19) compared to other psychotropics.

BACKGROUND: Current guidelines recommend using direct oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF), but head-to-head trial data do not exist to guide the choice of DOAC. OBJECTIVE: To do a large-scale comparison between all DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) in routine clinical practice. DESIGN: Multinational population-based cohort study. SETTING: Five standardized electronic health care databases, which covered 221 million people in France, Germany, the United Kingdom, and the United States. PARTICIPANTS: Patients who were newly diagnosed with AF from 2010 through 2019 and received a new DOAC prescription. MEASUREMENTS: Database-specific hazard ratios (HRs) of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between DOACs were estimated using a Cox regression model stratified by propensity score and pooled using a random-effects model. RESULTS: A total of 527 226 new DOAC users met the inclusion criteria (apixaban, n = 281 320; dabigatran, n = 61 008; edoxaban, n = 12 722; and rivaroxaban, n = 172 176). Apixaban use was associated with lower risk for GIB than use of dabigatran (HR, 0.81 [95% CI, 0.70 to 0.94]), edoxaban (HR, 0.77 [CI, 0.66 to 0.91]), or rivaroxaban (HR, 0.72 [CI, 0.66 to 0.79]). No substantial differences were observed for other outcomes or DOAC-DOAC comparisons. The results were consistent for patients aged 80 years or older. Consistent associations between lower GIB risk and apixaban versus rivaroxaban were observed among patients receiving the standard dose (HR, 0.72 [CI, 0.64 to 0.82]), those receiving a reduced dose (HR, 0.68 [CI, 0.61 to 0.77]), and those with chronic kidney disease (HR, 0.68 [CI, 0.59 to 0.77]). LIMITATION: Residual confounding is possible. CONCLUSION: Among patients with AF, apixaban use was associated with lower risk for GIB and similar rates of ischemic stroke or systemic embolism, ICH, and all-cause mortality compared with dabigatran, edoxaban, and rivaroxaban. This finding was consistent for patients aged 80 years or older and those with chronic kidney disease, who are often underrepresented in clinical trials.None.

It is known that younger patients treated with antipsychotics are at increased risk of metabolic events; however, it is unknown how this risk varies according to ethnicity, the class of antipsychotic and the specific product used, and by age group. We conducted a multinational sequence symmetry study in Asian populations (Hong Kong, Japan, Korea, Taiwan and Thailand) and non-Asian populations (Australia and Denmark) to evaluate the metabolic events associated with antipsychotics in both Asian and non-Asian populations, for typical and atypical antipsychotics, and by the subgroups of children and adolescents, and young adults. Patients aged 6–30 years newly initiating oral antipsychotic drugs were included. We defined a composite outcome for metabolic events which included dyslipidemia, hypertension and hyperglycemia. We calculated the sequence ratio (SR) by dividing the number of people for whom a medicine for one of the outcome events was initiated within a 12-month period after antipsychotic initiation by the number before antipsychotic initiation. This study included 346,904 antipsychotic initiators across seven countries. Antipsychotic use was associated with an increased risk of composite metabolic events with a pooled adjusted SR (ASR) of 1.22 (95% CI 1.00–1.50). Pooled ASRs were similar between Asian (ASR, 1.22; 95% CI 0.88–1.70) and non-Asian populations (ASR, 1.22; 95% CI 1.04–1.43). The pooled ASR for typical and atypical antipsychotics was 0.98 (95% CI 0.85–1.12) and 1.24 (95% CI 0.97–1.59), respectively. No difference was observed in the relative effect in children and adolescents compared to young adults. The risk of metabolic events associated with antipsychotics use was similar in magnitude in Asian and non-Asian populations despite the marked difference in drug utilization patterns Refereed/Peer-reviewed

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.

Aims The risk of antipsychotic-associated cardiovascular and metabolic events may differ among countries, and limited real-world evidence has been available comparing the corresponding risks among children and young adults. We, therefore, evaluated the risks of cardiovascular and metabolic events in children and young adults receiving antipsychotics. Methods We conducted a multinational self-controlled case series (SCCS) study and included patients aged 6–30 years old who had both exposure to antipsychotics and study outcomes from four nationwide databases of Taiwan (2004–2012), Korea (2010–2016), Hong Kong (2001–2014) and the UK (1997–2016) that covers a total of approximately 100 million individuals. We investigated three antipsychotics exposure windows (i.e., 90 days pre-exposure, 1–30 days, 30–90 days and 90 + days of exposure). The outcomes were cardiovascular events (stroke, ischaemic heart disease and acute myocardial infarction), or metabolic events (hypertension, type 2 diabetes mellitus and dyslipidaemia). Results We included a total of 48 515 individuals in the SCCS analysis. We found an increased risk of metabolic events only in the risk window with more than 90-day exposure, with a pooled IRR of 1.29 (95% CI 1.20–1.38). The pooled IRR was 0.98 (0.90–1.06) for 1–30 days and 0.88 (0.76–1.02) for 31–90 days. We found no association in any exposure window for cardiovascular events. The pooled IRR was 1.86 (0.74–4.64) for 1–30 days, 1.35 (0.74–2.47) for 31–90 days and 1.29 (0.98–1.70) for 90 + days. Conclusions Long-term exposure to antipsychotics was associated with an increased risk of metabolic events but did not trigger cardiovascular events in children and young adults.