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Background: Clozapine is widely regarded as a highly efficacious psychotropic drug that is largely underused worldwide. Recent disproportionality analyses and nationwide case-control studies suggested a potential association between clozapine use and hematological malignancy (HM). Nevertheless, the absolute rate difference is not well-established due to the absence of analytic cohort studies. The clinical significance of such a potential risk remains unclear. Methods and findings: We extracted data from a territory-wide public healthcare database from January 2001 to August 2022 in Hong Kong to conduct a retrospective cohort study of anonymized patients aged 18+ years with a diagnosis of schizophrenia who used clozapine or olanzapine (drug comparator with highly similar chemical structure and pharmacological mechanisms) for 90+ days, with at least 2 prior other antipsychotic use records within both groups. Weighted by inverse probability of treatment (IPTW) based on propensity scores, Poisson regression was used to estimate the incidence rate ratio (IRR) of HM between clozapine and olanzapine users. The absolute rate difference was also estimated. In total, 9,965 patients with a median follow-up period of 6.99 years (25th to 75th percentile: 4.45 to 10.32 years) were included, among which 834 were clozapine users. After IPTW, the demographic and clinical characteristics of clozapine users were comparable to those of olanzapine users. Clozapine users had a significant weighted IRR of 2.22 (95% confidence interval (CI) [1.52, 3.34]; p < 0.001) for HM compared to olanzapine users. The absolute rate difference was estimated at 57.40 (95% CI [33.24, 81.55]) per 100,000 person-years. Findings were consistent across subgroups by age and sex. Sensitivity analyses all supported the robustness of the results and showed good specificity to HM but no other cancers. The main limitation of this observational study is the potential residual confounding effects that could have arisen from the lack of randomization in clozapine or olanzapine use. Conclusions: Absolute rate difference in HM incidence associated with clozapine is small despite a 2-fold elevated rate. Given the rarity of HM and existing blood monitoring requirements, more restrictive indication for clozapine or special warnings may not be necessary. Yuqi Hu, Le Gao and colleagues compare the incidence of haematological malignancies between clozapine and olanzapine users using territory-wide electronic health records from Hong Kong public health facilities. Author summary: Why was this study done?: Preliminary epidemiologic evidence has been reported on an elevated risk of hematological malignancy (HM) associated with clozapine use. The clinical significance (or insignificance) of such a risk is yet to be determined. Analytic cohort studies are needed to estimate the rate difference, i.e., number of additional cases associated with clozapine use, in addition to rate ratios. What did the researchers do and find?: Using the territory-wide electronic health records from Hong Kong public healthcare facilities, we built a retrospective cohort to compare the incidence of HM between clozapine and olanzapine users. Similar with previous research, we found a 2-fold elevated rate of HM in clozapine users. Nevertheless, the rate difference between clozapine and olanzapine users were small, i.e., approximately 1 additional case of HM in every 1,700 person-year of exposure to clozapine. What do these findings mean?: The previously observed elevated risk of HM associated with clozapine is supported by territory-wide data in Hong Kong. The absolute rate difference is small and, given existing risk mitigation measures for hematological abnormalities, does not necessitate additional restrictions on the indication of clozapine or special warnings. As the assignment of clozapine versus olanzapine use in this cohort was not randomized, there may be underlying factors that are related to both clozapine use (versus olanzapine) and HM that gave rise to the observed association but were not considered. [ABSTRACT FROM AUTHOR]

Introduction: Both daily and on-demand regimens have been proven effective for pre-exposure prophylaxis (PrEP) against HIV in men who have sex with men (MSM). We aimed to compare the two regimens on their coverage of condomless anal intercourse (CLAI) in MSM. Methods: A randomized, controlled, open-label, crossover trialwas conducted in a teaching hospitalin Hong Kong. Participants were sexually active HIV-negative MSM aged 18 years or above with normalrenalfunction and without chronic hepatitis B infection. Oraltenofovir disoproxilfumarate 300 mg/emtricitabine 200 mg (TDF/FTC) tablets were prescribed for PrEP. After a 2-week lead-in with daily TDF/FTC for treatment-na[up arrow]ve MSM for tolerance assessment, participants were randomly assigned in a 1:1 ratio with a block size of four to either daily-first or on-demand-first arm based on the IPERGAY study, for receiving PrEP for 16 weeks, then crossed-over to the alternative regimen for another 16 weeks. The primary outcome was the proportion of days with PrEP-covered CLAI by intention-to-treat analysis. The trial is registered with the CCRB Clinical Trials Registry, CUHK, CUHKCCRB00606, and is closed to accrual. Results: Between 25 August 2018 and 23 March 2019, 119 eligible participants were assigned to daily-first arm (n = 59) and on-demand-first arm (n = 60) with an 87% overallcompletion rate (n = 103). With 96% and 54% of days on PrEP during daily and on-demand periods, respectively, the proportion of days with PrEP-covered CLAI between two arms were not statistically different (92% vs. 92%, p = 0.93). About half (47%) were diagnosed with at least one episode of incident sexually transmitted infection. Mild and time-limited adverse events, including diarrhoea, headache, nausea and dizziness, were reported in 37 (31%) and 10 (8%) during the daily and on-demand periods, respectively. At the end of the study, a similar proportion favoured daily or on-demand regimen. Conclusions: High prevention-effective adherence, as reflected from the coverage of CLAI, was achievable by either daily or on-demand PrEP among MSM, albeit a higher number of tablets taken for daily PrEP. As both regimens were well accepted, a flexible approach adopting either or both regimens with possible switching is warranted in order to suit individual health needs. Keywords: Asia; clinicaltrials; crossover design; HIV prevention trials; men who have sex with men; PrEP, 1 | INTRODUCTION Pre-exposure prophylaxis (PrEP) with co-formulated tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) is a proven form of biomedical HIV prevention. Following the demonstration of its effectiveness in iPrEx, [...]

Objective: Existing data on prenatal antidepressant prescribing patterns are mostly derived from Western countries, with limited research assessing antidepressant continuation and reinitiation during pregnancy. This study aimed to examine antidepressant prescribing practice among Chinese pregnant women in Hong Kong. Methods: This population-based study identified women aged 15–50 years who delivered their first and singleton child, and had redeemed at least one antidepressant prescription within 3 months pre-pregnancy and/or during pregnancy between 2003 and 2018, using data from the health-record database of Hong Kong public healthcare services. Antidepressant utilization patterns before and during pregnancy, and factors associated with antidepressant continuation and reinitiation following medication discontinuation were evaluated. Results: Of 466,358 pregnancies, 3019 (0.67%) received antidepressants within 3 months of pre-pregnancy and/or during pregnancy, and 2700 (0.58%) had prenatal antidepressant use. There was a significant rising trend of prenatal antidepressant use over time (0.6% in 2003 to 1.3% in 2018; odds ratio: 1.09, 95% confidence interval = [1.08, 1.10], p < 0.001). A consistent pattern of decreasing overall antidepressant use from 3 months pre-pregnancy to the second trimester was observed, followed by a slight increase in the third trimester. Almost half (n = 949, 49.5%) of 1918 women on antidepressants in 3 months pre-pregnancy continued treatment beyond the first trimester. A total of 8.2% that discontinued antidepressants in 3 months pre-pregnancy or in the first trimester reinitiated treatment in the later stage of pregnancy. Older age at conception (⩾35 years), recent calendar year of delivery (2015–2018), pre-existing depression/anxiety disorders, longer-term pre-pregnancy antidepressant treatment and pre-pregnancy prescription of other psychotropics were significantly associated with antidepressant continuation. Antidepressant reinitiation was predicted by pre-existing depression/anxiety disorders. Conclusions: Our results that prenatal antidepressant use is increasingly prevalent and half of pregnant women discontinued antidepressants 3 months before or after conception underscore the need for future research to clarify the risk and benefit of antidepressant continuation versus discontinuation to facilitate development of evidence-based guidelines, so as to optimize maternal and fetal outcomes. [ABSTRACT FROM AUTHOR]

The Hong Kong HIV Cohort Database is an observational cohort including all patients enrolled in 2 HIV specialist clinical services in Hong Kong. Basic demographics, HIV transmission category, and the diagnoses of AIDS were captured using a standardized template. As of December 2006, 2132 HIV cases had been registered in the database, representing two thirds of all reports submitted to the government’s surveillance system. Non-Chinese and young females ≤24 years were less represented in the cohort. Description of cohort cases was, however, more complete in terms of transmission category and presentation with AIDS-defining illnesses. Overall, Pneumocystis jirovecci, tuberculosis, and systemic mycosis accounted for a majority of AIDS cases within 3 months of HIV diagnosis. There was a gradual rise of HIV positive men having sex with men in the cohort, notably after 2002, an observation also made in other Asian countries. [ABSTRACT FROM PUBLISHER]

People with depression have increased premature mortality and elevated prevalence of diabetes-mellitus compared to general population. However, risk of mortality and diabetes-related complications among patients with depression and co-occurring diabetes is under-studied. This population-based propensity score-matched (1:10) cohort study identified 12,175 patients with pre-existing depression and incident-diabetes (depression-diabetes group) and 117,958 patients with incident-diabetes only (diabetes-only group) between 2002 and 2021 in Hong-Kong, using territory-wide medical-record database of public-healthcare services, to investigate whether depression increased the risk of overall mortality, complications and post-complication mortality in people with diabetes. Associations of depression with all-cause mortality, complication and post-complication all-cause mortality rates were examined by Cox proportional-hazards model. Complications were assessed by Diabetes-Complications-Severity-Index (DCSI). Associations of complications, in terms of DCSI scores (complication burden), specific types and two-way combinations of complications (complication patterns) with all-cause mortality rate in depression were also examined. Our results showed that depression-diabetes group exhibited increased all-cause mortality risk (adjusted hazards-ratio: 1.06 [95 %CI: 1.02-1.10]) relative to diabetes-only group, particularly among men and older age group, with significantly higher rate of experiencing neuropathy (1.44 [1.27-1.62]) and metabolic complications (1.30 [1.09-1.56]) and lower likelihood of peripheral-vascular complications, retinopathy and nephropathy, albeit comparable macrovascular and microvascular complication rates. The mortality-rate-ratio for patients with depression and diabetes was significantly higher than patients with diabetes-only at a low level of complication burden. In conclusion, depression patients with co-occurring diabetes are at increased risk of excess mortality. Further research is warranted to improve diabetes-related outcomes and reduce mortality gap in this vulnerable population., Competing Interests: Conflicts of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (Copyright © 2024. Published by Elsevier B.V.)

Studies demonstrated increased obstetric and neonatal complications in women with schizophrenia-spectrum disorder (SSD), but most inadequately addressed confounders and rarely considered antipsychotic effects. We conducted a meta-analysis and a population-based cohort study evaluating associations of adverse obstetric/neonatal outcomes with SSD and prenatal antipsychotic use. In the meta-analysis, we searched four databases from inception to October-31-2023 and generated pooled risk estimates using random-effect models. In the cohort study, we identified women aged 15-50 years with SSD-diagnosis from electronic-heath-record database of public healthcare-services who delivered first/singleton children between 2003 and 2018 in Hong Kong. Propensity-score weighted regression-analyses incorporating important confounders including maternal pre-existing and gestational morbidities, substance/alcohol abuse, and psychotropic use, were performed to assess risk of adverse obstetric/neonatal outcomes in SSD-women versus non-SSD-women, and subsequently treated-SSD and untreated-SSD subgroups to disentangle effects of SSD from antipsychotic exposure. The meta-analysis (studies = 18, women = 37,214,330, including 42,926 SSD-women) found significant associations of SSD with 12 of 17 analyzed negative obstetric/neonatal outcomes (with pooled relative risk ranged:1.12-2.10), including placental complications, induced labor, Caesarean delivery, fetal distress, stillbirth, preterm birth, small-for-gestational-age, low birth weight, low APGAR scores, neonatal and post-neonatal deaths. However, the cohort study (466,358 women, including 804 SSD-women) revealed that elevated risk of most study outcomes in unadjusted-models were markedly-attenuated or became non-significant in propensity-score weighted adjusted-models, except index-delivery hospitalization ≥7 days (odds ratio [OR] = 1.76 [95% CI = 1.33-2.34]), preterm birth (OR = 1.48 [95% CI = 1.09-2.00]) and neonatal special-care admission (OR = 1.65 [95% CI = 1.35-2.01]). Apart from higher neonatal special-care admission in treated-SSD than untreated-SSD women (OR = 1.75 [95% CI = 1.23-2.52]), no significant between-group differences emerged in other outcomes. In sum, elevated risk of most obstetric/neonatal complications reported in SSD-women might largely be explained by maternal physical comorbidities, substance/alcohol use disorders and other confounders. Interventions targeting modifiable maternal risk factors should be incorporated in prenatal care for SSD-women to minimize avoidable adverse outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The Hong Kong HIV Cohort Database is an observational cohort including all patients enrolled in 2 HIV specialist clinical services in Hong Kong. Basic demographics, HIV transmission category, and the diagnoses of AIDS were captured using a standardized template. As of December 2006, 2132 HIV cases had been registered in the database, representing two thirds of all reports submitted to the government's surveillance system. Non-Chinese and young females≤24 years were less represented in the cohort. Description of cohort cases was, however, more complete in terms of transmission category and presentation with AIDS-defining illnesses. Overall, Pneumocystis jirovecci, tuberculosis, and systemic mycosis accounted for a majority of AIDS cases within 3 months of HIV diagnosis. There was a gradual rise of HIV positive men having sex with men in the cohort, notably after 2002, an observation also made in other Asian countries.