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Despite growing concern about reproductive safety of psychotropic drugs, there is a paucity of research assessing prenatal prescribing practices for bipolar disorder (BD). This population-based cohort study identified women aged 15-50 years with BD diagnosis, who delivered their first and singleton child between 2003 and 2018 in Hong Kong, with an aim to examine temporal trends and predictors of prenatal psychotropic drug use as well as drug utilization patterns before and during pregnancy were evaluated. Data were retrieved from territory-wide medical-record database of public healthcare services. Of 302 identified women, 202 (66.9%) and 180 (59.6%) redeemed at least 1 prescription for psychotropic drugs in 12 months pre-pregnancy and during pregnancy, respectively. Psychotropic drug treatment (OR = 16.14 [95% CI: 8.79-29.65]) and psychiatric admission (OR = 4.12 [95% CI: 1.66-10.24]) within 12 months pre-pregnancy were associated with prenatal drug use. Second-generation antipsychotic use during pregnancy increased over time, while prenatal use of lithium, anti-epileptics and first-generation-antipsychotics showed declining trend. Use of psychotropic drugs progressively decreased across pre-pregnancy and trimesters of pregnancy. Forty-two (23.3%) women received polypharmacy during pregnancy. Antidepressant use accounted for 17% of all monotherapy episodes. A significant proportion of women exposed to valproate in 12 months pre-pregnancy (27.2%) and first-trimester (16%). In conclusion, our results generally indicate trajectories of reduced psychotropic drug use across pregnancy. Deviations between real-world prescribing patterns and treatment guidelines underscore the need for comprehensive review of current clinical practices. Further research clarifying relationships of prenatal psychotropic drug exposure with maternal and fetal outcomes is warranted., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper., (Copyright © 2022 Elsevier B.V. and ECNP. All rights reserved.)

Background: Stimulation of immunity by vaccination may elicit adverse events. There is currently inconclusive evidence on the relationship between herpes zoster related hospitalization and COVID-19 vaccination. This study aimed to evaluate the effect of inactivated virus (CoronaVac, Sinovac) and mRNA (BNT162b2, BioNTech/Fosun Pharma) COVID-19 vaccine on the risk of herpes zoster related hospitalization., Methods: Self-controlled case series (SCCS) analysis was conducted using the data from the electronic health records in Hospital Authority and COVID-19 vaccination records in the Department of Health in Hong Kong. We conducted the SCCS analysis including patients with a first primary diagnosis of herpes zoster in the hospital inpatient setting between February 23 and July 31, 2021. A confirmatory analysis by nested case-control method was also conducted. Each herpes zoster case was randomly matched with ten controls according to sex, age, Charlson comorbidity index, and date of hospital admission. Conditional Poisson regression and logistic regression models were used to assess the potential excess rates of herpes zoster after vaccination., Findings: From February 23 to July 31, 2021, a total of 16 and 27 patients were identified with a first primary hospital diagnosis of herpes zoster within 28 days after CoronaVac and BNT162b2 vaccinations. The incidence of herpes zoster was 7.9 (95% Confidence interval [CI]: 5.2-11.5) for CoronaVac and 7.1 (95% CI: 4.1-11.5) for BNT162b2 per 1,000,000 doses administered. In SCCS analysis, CoronaVac vaccination was associated with significantly higher risk of herpes zoster within 14 days after first dose (adjusted incidence rate ratio [aIRR]=2.67, 95% CI: 1.08-6.59) but not in other periods afterwards compared to the baseline period. Regarding BNT162b2 vaccination, a significantly increased risk of herpes zoster was observed after first dose up to 14 days after second dose (0-13 days after first dose: aIRR=5.23, 95% CI: 1.61-17.03; 14-27 days after first dose: aIRR=5.82, 95% CI: 1.62-20.91; 0-13 days after second dose: aIRR=5.14, 95% CI: 1.29-20.47). Using these relative rates, we estimated that there has been an excess of approximately 5 and 7 cases of hospitalization as a result of herpes zoster after every 1,000,000 doses of CoronaVac and BNT162b2 vaccination, respectively. The findings in the nested case control analysis showed similar results., Interpretation: We identified an increased risk of herpes zoster related hospitalization after CoronaVac and BNT162b2 vaccinations. However, the absolute risks of such adverse event after CoronaVac and BNT162b2 vaccinations were very low. In locations where COVID-19 is prevalent, the protective effects on COVID-19 from vaccinations will greatly outweigh the potential side effects of vaccination., Funding: The project was funded by Research Grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (Ref. No.COVID19F01). FTTL (Francisco Tsz Tsun Lai) and ICKW (Ian Chi Kei Wong)'s posts were partly funded by D 2 4H; hence this work was partly supported by AIR@InnoHK administered by Innovation and Technology Commission., Competing Interests: EYFW has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grants Council, outside the submitted work. CSLC has received grants from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen; personal fee from Primevigilance Ltd.; outside the submitted work. FTTL has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council and has received research grants from Food and Health Bureau of the Government of the Hong Kong SAR, outside the submitted work. EWYC reports honorarium from Hospital Authority, grants from Research Grants Council (RGC, Hong Kong), grants from Research Fund Secretariat of the Food and Health Bureau, grants from National Natural Science Fund of China, grants from Wellcome Trust, grants from Bayer, grants from Bristol-Myers Squibb, grants from Pfizer, grants from Janssen, grants from Amgen, grants from Takeda, grants from Narcotics Division of the Security Bureau of HKSAR, outside the submitted work. XL has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, research and educational grants from Janssen and Pfizer; internal funding from University of Hong Kong; consultancy fee from Merck Sharp & Dohme, unrelated to this work. CKHW reports the receipt of General Research Fund, Research Grant Council, Government of Hong Kong SAR; EuroQol Research Foundation, all outside the submitted work. ICKW reports research funding outside the submitted work from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council, and the Hong Kong Health and Medical Research Fund, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, and also received speaker fees from Janssen and Medice in the previous 3 years. He is also an independent non-executive director of Jacobson Medical in Hong Kong., (© 2022 The Author(s).)

Purpose: Schizophrenia is associated with increased premature mortality and physical morbidity. This study aimed to examine prevalence of pre-existing chronic physical diseases, and association between physical multimorbidity burden and mortality rates among patients with newly diagnosed schizophrenia., Methods: This population-based cohort study investigated patients with first-recorded diagnosis of schizophrenia between January 2006 and December 2016, using territory-wide medical-record database of public healthcare service in Hong Kong. Physical morbidities were measured by Charlson Comorbidity Index (CCI), taking into consideration both number and severity of physical diseases, and were grouped into nine broad disease categories for analyses. Physical multimorbidity burden was stratified into three levels according to CCI of 0, 1 or ≥ 2. Cox proportional hazards regression models were used to examine associations of physical multimorbidity with mortality rates., Results: Of the 13,945 patients, 8.6% (n = 1207) had pre-existing physical morbidity. Patients with physical morbidity exhibited elevated all-cause mortality rate relative to those without physical morbidity [adjusted HR 2.38 (95% CI 2.04-2.77)]. Gastrointestinal/liver diseases, diabetes and cardiovascular diseases constituted the three most frequently diagnosed physical morbidities, whereas cancers displayed the highest all-cause mortality rate. An increase in physical multimorbidity burden was associated with increased all-cause mortality rate [CCI = 1: 1.98 (1.64-2.40); CCI ≥ 2: 3.08 (2.51-3.77), CCI = 0 as reference]., Conclusion: Schizophrenia patients with pre-existing physical morbidity had two-fold increased risk of premature mortality compared to those without physical morbidity. Physical multimorbidity confers incremental impact on excess mortality. Early detection and intervention of physical morbidity in the initial phase of schizophrenia is necessary to reduce avoidable mortality., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To evaluate the clinical and humanistic outcomes of a community pharmacist-involved collaborative care model in diabetes management., Methods: This was a parallel arm, open-label, multi-centre randomized controlled trial conducted over 6 months. Subjects with type 2 diabetes, HbA1c ≥ 7.0% (53 mmol/mol) and taking ≥ 5 medications were included. Participants were randomized into intervention (collaborative care) and control groups (physician-centric care). The intervention included medication therapy management and telephonic follow-up with visits to family physicians, nurses, and dietitians. Clinical outcomes included changes in HbA1c, systolic blood pressure (SBP), lipids, and hypoglycaemic incidences. Humanistic outcomes included self-care capabilities and quality of life. Linear mixed models were constructed. Intention-to-treat analyses, with sensitivity analyses, were conducted., Results: A total of 264 participants were randomized (intervention: 131, control: 133). Significantly greater reduction in HbA1c was observed in the intervention group (intervention: -0.32% (-3.52 mmol/mol) vs. control: -0.06% (-0.66 mmol/mol), p = 0.038). Changes in SBP, lipids, and incidences of hypoglycaemia were not significant over 6 months between both groups. Significantly greater improvements in self-management (p < 0.001) and quality of life (p = 0.003) were observed within the intervention group., Conclusion: Partnering community pharmacists in a collaborative care team improved glycaemic control, quality of life and self-care capabilities of patients with diabetes and polypharmacy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: HLA-B*15:11 is associated with carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions (SCARs) in Japanese and some Asian populations, but such data remains relatively limited in Chinese. Routine HLA-B*15:02 screening is mandatory before CBZ commencement, however, SCARs related to CBZ were still observed in non-HLA*B-15:02 carriers., Objective: We aimed to find out the prevalence of HLA-B*15:11 in Chinese patients and its associations with CBZ-induced SCARs., Method: We screened 8,328 blood samples collected for HLA allele typing before CBZ commencement during the period of January 2014 to December 2019. In HLA-B*15:02 negative Chinese patients, HLA-B*15:11 status were further screened, and the incidence of SCARs in the CBZ group was compared with the control group without CBZ use., Result: In this cohort, 1416 out of 8328 patients (17%) tested HLA-B*15:02 positive and were advised to avoid CBZ, while 80 (0.96%) were found to be HLA-B*15:11 positive. In 6911 (83%) patients who tested HLA-B*15:02 negative, 70 (1.01%) were HLA-B*15:11 positive. Five out of 70 (7.14%) patients had SCARs. The incidence of SCARs in HLA-B*15:11 carriers who received CBZ was significantly higher than those without CBZ (17.4% [4/23] vs. 2.13% [1/47], P = 0.037*). The odds ratio was 9.68 (95% CI 1.02-92.4, P = 0.048*). These included: one Stevens-Johnson syndrome (SJS), two DRESS, and one MPE after CBZ use, while one developed MPE after phenytoin use in control., Conclusion: HLA-B*15:11 is a potential risk factor of CBZ-induced SCARs in HLA-B*15:02 negative Chinese patients. Further screening of HLA-B*15:11 status in those HLA-B*15:02 negative patients is recommended to avoid undesirable SCARs., (© 2021 the International Society of Dermatology.)

Delayed hypersensitivity reaction of penicillin is commonly seen, but never reported in pyridium. This case illustrates a patient with delayed hypersensitivity reaction after the use of augmentin and pyridium. Skin patch test, surprisingly, confirmed pyridium delayed hypersensitivity., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest., (Copyright © 2022. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Schizophrenia is associated with increased prevalence of diabetes. However, risk of diabetes complications as well as the impact of complication burden and patterns on subsequent mortality risk in schizophrenia patients with co-existing diabetes is understudied. This population-based, propensity-score matched (1:10) cohort study identified 6991 patients with incident diabetes and pre-existing schizophrenia and 68,682 patients with incident diabetes only (comparison group) between 2001 and 2016 in Hong Kong, using territory-wide medical-record database of public healthcare services. Complications were measured by Diabetes Complications Severity Index (DCSI), which stratified complication burden into 6 levels (DCSI score=0, 1, 2, 3, 4, or ≥5). Associations of diabetes complications, in terms of DCSI scores (complication burden), specific types and two-way combinations of complications (complication patterns), with all-cause mortality rate in schizophrenia were evaluated using Cox proportional-hazards models. Schizophrenia group had comparable macrovascular (adjusted OR 0.99 [95% CI 0.92-1.06]) and lower microvascular (0.79 [0.73-0.86]) complication rates relative to comparison group. Mortality risk ratio for schizophrenia was elevated at all complication burden levels, which conferred incremental impact on excess mortality in both groups. Cardiovascular diseases (1.60 [1.45-1.77]) and cerebrovascular-metabolic diseases (2.74 [1.25-5.99]) were associated with the highest differential mortality in schizophrenia among various specific complications and complication combinations, respectively. Our results indicate that schizophrenia patients with co-existing diabetes are at increased risk of excess mortality relative to those with diabetes alone, regardless of complication burden levels. Implementation of multilevel, targeted interventions is needed to improve diabetes-related outcomes and reduce mortality gap in this vulnerable population., Competing Interests: Declaration of Competing Interest The authors declared no conflicts of interest in relation to the subject of this study., (Copyright © 2021. Published by Elsevier B.V.)

Background and Objectives: Facial melasma is a disfiguring pigmentation and occurs frequently with aging skin. Topical treatment alone was often suboptimal. A recent study showed that fractional picosecond laser has promising result in benign pigmentary lesions. This study aims to investigate the efficacy and safety of 1064 nm picosecond laser in treatment of facial melasma and skin rejuvenation in Asian skin., Study Design/materials and Methods: Patients of Asian descent seeking treatment for facial melasma and skin rejuvenation were screened and recruited. Each patient received up to nine laser treatments at 4-6 weeks intervals with a fractionated nonablative 1064 nm picosecond laser. Baseline and posttreatment modified Melasma Area Severity Index (mMASI) and Global Aesthetic Improvement Scale (IGAS) were assessed by blinded investigators based on the clinical photographs. Subject overall satisfaction was assessed by the questionnaires after treatment. All adverse events were documented., Results: Twenty patients were recruited with a median age of 52.7 ± 8.2 years. Three subjects had Fitzpatrick skin type III and 17 had skin type IV. All subjects received nine laser sessions. Over 70% of patients were satisfied with the treatment outcomes. There was a statistically significant improvement in mMASI which reduced from 10.8 at baseline to 2.7 and 3.6 at 6 and 12 weeks post-treatment, respectively (both P < 0.01). For skin rejuvenation, 70% reported at least a moderate improvement at 6 weeks of post-treatment. No major side-effect was reported. Erythema was the most frequent transient response, while some reported edema (1.1%). Both resolved spontaneously. None reported hypo- or hyperpigmentation after treatment. The overall mean pain scare (VAS) was 1.92., Conclusion: Fractionated non-ablative 1064 nm picosecond laser was effective in treatment of melasma and skin rejuvenation. It was also safe and well tolerated. Importantly, there was no hypo or hyperpigmentation reported. Lasers Surg. Med. 00:00-00, 2021. © 2021 Wiley Periodicals LLC., (© 2021 Wiley Periodicals LLC.)

Background: The relationship between the subtypes of psychotic experiences (PEs) and common mental health symptoms remains unclear. The current study aims to establish the 12-month prevalence of PEs in a representative sample of community-dwelling Chinese population in Hong Kong and explore the relationship of types of PEs and common mental health symptoms., Method: This is a population-based two-phase household survey of Chinese population in Hong Kong aged 16-75 (N = 5719) conducted between 2010 and 2013 and a 2-year follow-up study of PEs positive subjects (N = 152). PEs were measured with Psychosis Screening Questionnaire (PSQ) and subjects who endorsed any item on the PSQ without a clinical diagnosis of psychotic disorder were considered as PE-positive. Types of PEs were characterized using a number of PEs (single v. multiple) and latent class analysis. All PE-positive subjects were assessed with common mental health symptoms and suicidal ideations at baseline and 2-year follow-up. PE status was also assessed at 2-year follow-up., Results: The 12-month prevalence of PEs in Hong Kong was 2.7% with 21.1% had multiple PEs. Three latent classes of PEs were identified: hallucination, paranoia and mixed. Multiple PEs and hallucination latent class of PEs were associated with higher levels of common mental health symptoms. PE persistent rate at 2-year follow-up was 15.1%. Multiple PEs was associated with poorer mental health at 2-year follow-up., Conclusions: Results highlighted the transient and heterogeneous nature of PEs, and that multiple PEs and hallucination subtype of PEs may be specific indices of poorer common mental health.

Objective: We aim to provide an up-to-date systematic review and meta-analysis of the effects of cognitive stimulation (CS) on cognition, depressive symptoms, and quality of life in persons with dementia. Factors affecting the treatment effect were examined., Methods: A literature search was performed on databases of MEDLINE, EMBASE, PsycINFO, CINAHL Plus, and Cochrane Library up to 7 March 2019. Only randomised controlled trials investigating the effects of CS in persons with dementia were included. The outcome measures were cognitive function, depressive symptoms, and quality of life., Results: 20 randomised controlled trials with a total of 1251 participants (intervention group: 674; control group: 577) were included for meta-analysis. Most participants had mild to moderate dementia. CS had a significant positive small-to-moderate effect on cognition (Hedges's g = 0.313, p < 0.001). Heterogeneity of CS was low to moderate (Q=30.5854, df=19, p < 0.05, I2 = 37.877%). Inconclusive results were found for depressive symptoms and quality of life., Conclusion: CS has a significant positive effect on cognitive function, but its effect on depressive symptoms and quality of life was inconclusive. Future studies with more robust methodology establishing evidence of its efficacy are required., Competing Interests: All authors have disclosed no conflicts of interest. Dr Gloria Wong is the Director of Training of the CST-HK programme.

Background: Schizophrenia patients have markedly elevated prevalence of diabetes compared with the general population. However, risk of mortality and diabetes-related complications among schizophrenia patients with co-occurring diabetes is understudied., Aims: We investigated whether schizophrenia increased the risk of overall mortality, complications and post-complication mortality in people with diabetes., Method: This population-based, propensity-score matched (1:10) cohort study identified 6991 patients with incident diabetes and pre-existing schizophrenia and 68 682 patients with incident diabetes only between 2001 and 2016 in Hong Kong using a medical record database of public healthcare services. Association between schizophrenia and all-cause mortality was examined with a Cox proportional hazards model. Effect of schizophrenia on first-year complication occurrence following diabetes diagnosis and post-complication mortality rates were evaluated., Results: Schizophrenia was associated with increased all-cause mortality (adjusted hazards ratio [aHR] 1.11, 95% CI 1.05-1.18), particularly among men and older age groups. Schizophrenia patients with diabetes had higher metabolic complication rate (aHR 1.99, 95% CI 1.63-2.42), lower microvascular complication rate (aHR 0.75, 95% CI 0.65-0.86) and comparable macrovascular complication rate (aHR 0.93, 95% CI 0.85-1.03), relative to patients with diabetes only. Among patients with diabetes complications, schizophrenia was associated with elevated all-cause mortality after macrovascular (aHR 1.19, 95% CI 1.04-1.37) and microvascular (aHR 1.33, 95% CI 1.08-1.64) complications. Gender-stratified analyses revealed that a significant effect of schizophrenia on heightened post-complication mortality was observed in men only., Conclusions: Schizophrenia patients with co-occurring diabetes are at increased risk of excess mortality, including post-complication mortality. Further research identifying effective interventions is warranted to optimise diabetes-related outcomes in this vulnerable population.

Background: Rumination and overgeneral autobiographical memory are dysfunctional cognitions commonly found in older adults with depression. The theoretical underpinnings of mindfulness-based cognitive therapy (MBCT) address the ruminative tendencies and the non-specific retrieval of autobiographical memories. This study aims to examine the efficacy and cognitive mechanisms of MBCT in older adults with active depressive symptoms., Methods: 57 older adults (mean age, 70 years) with normal cognition and mild to moderate depressive symptoms were randomly allocated to either the MBCT group or the active control group for 8 weeks. The MBCT group consisted of eight 2-hour weekly sessions and a 7-hour full-day retreat, with different themes for each class, guided mindfulness exercises, feedback and discussion, homework review, and psychoeducation. The active control group comprised a 1-hour physical exercise and a standardised health education of the specific theme with group discussion (eg fall prevention, chronic pain). Participants were assessed before and after the 8-week intervention for four outcome measures: the Hamilton Depression Rating Scale (HAMD), the Ruminative Response Scale (RRS), the Autobiographical Memory Test (AMT), and the Mindful Attention Awareness Scale (MAAS)., Results: There was a significant reduction in severity of depressive symptoms (HAMD score) in both the MBCT group (F(1, 27) = 35.9, p < 0.001, η 2 = 0.57) and the active control group (F(1, 28) = 9.29, p < 0.01, η 2 = 0.24), but only the MBCT group showed substantial improvements in autobiographical memory specificity (AMT score), rumination (RRS score), and mindfulness (MAAS score)., Conclusion: Although both MBCT and active control programme decrease the severity of depressive symptoms in older adults, only MBCT improves AMS, rumination, and mindfulness. Our findings provide empirical support for the theoretical underpinnings of MBCT. Older adults with more severe depression and more severe dysfunctional cognition may benefit more from the specific therapeutic effects of MBCT., Competing Interests: The authors have no conflict of interest to disclose.

Objectives: The co-occurrence of different classes of population-level stressors, such as social unrest and public health crises, is common in contemporary societies. Yet, few studies explored their combined mental health impact. The aim of this study was to examine the impact of repeated exposure to social unrest-related traumatic events (TEs), coronavirus disease 2019 (COVID-19) pandemic-related events (PEs), and stressful life events (SLEs) on post-traumatic stress disorder (PTSD) and depressive symptoms, and the potential mediating role of event-based rumination (rumination of TEs-related anger, injustice, guilt, and insecurity) between TEs and PTSD symptoms., Methods: Community members in Hong Kong who had utilized a screening tool for PTSD and depressive symptoms were invited to complete a survey on exposure to stressful events and event-based rumination., Results: A total of 10,110 individuals completed the survey. Hierarchical regression analysis showed that rumination, TEs, and SLEs were among the significant predictors for PTSD symptoms (all P < 0.001), accounting for 32% of the variance. For depression, rumination, SLEs, and PEs were among the significant predictors (all P < 0.001), explaining 24.9% of the variance. Two-way analysis of variance of different recent and prior TEs showed significant dose-effect relationships. The effect of recent TEs on PTSD symptoms was potentiated by prior TEs ( P = 0.005). COVID-19 PEs and prior TEs additively contributed to PTSD symptoms, with no significant interaction ( P = 0.94). Meanwhile, recent TEs were also potentiated by SLEs ( P = 0.002). The effects of TEs on PTSD symptoms were mediated by rumination (β = 0.38, standard error = 0.01, 95% confidence interval: 0.36 to 0.41), with 40.4% of the total effect explained. All 4 rumination subtypes were significant mediators., Conclusions: Prior and ongoing TEs, PEs, and SLEs cumulatively exacerbated PTSD and depressive symptoms. The role of event-based rumination and their interventions should be prioritized for future research.

Aims: Bipolar disorder is associated with premature mortality, but evidence is mostly derived from Western countries. There has been no research evaluating shortened lifespan in bipolar disorder using life-years lost (LYLs), which is a recently developed mortality metric taking into account illness onset for life expectancy estimation. The current study aimed to examine the extent of premature mortality in bipolar disorder patients relative to the general population in Hong Kong (HK) in terms of standardised mortality ratio (SMR) and excess LYLs, and changes of mortality rate over time., Methods: This population-based cohort study investigated excess mortality in 12 556 bipolar disorder patients between 2008 and 2018, by estimating all-cause and cause-specific SMRs, and LYLs. Trends in annual SMRs over the 11-year study period were assessed. Study data were retrieved from a territory-wide medical-record database of HK public healthcare services., Results: Patients had higher all-cause [SMR: 2.60 (95% CI: 2.45-2.76)], natural-cause [SMR: 1.90 (95% CI: 1.76-2.05)] and unnatural-cause [SMR: 8.63 (95% CI: 7.34-10.03)] mortality rates than the general population. Respiratory diseases, cardiovascular diseases and cancers accounted for the majority of deaths. Men and women with bipolar disorder had 6.78 (95% CI: 6.00-7.84) years and 7.35 (95% CI: 6.75-8.06) years of excess LYLs, respectively. The overall mortality gap remained similar over time, albeit slightly improved in men with bipolar disorder., Conclusions: Bipolar disorder is associated with increased premature mortality and substantially reduced lifespan in a predominantly Chinese population, with excess deaths mainly attributed to natural causes. Persistent mortality gap underscores an urgent need for targeted interventions to improve physical health of patients with bipolar disorder.

Psychotic disorders are associated with premature mortality, but research was primarily based on Western countries and rarely examined non-affective psychoses other than schizophrenia (ONAP). This population-based cohort study investigated excess mortality in 46 896 schizophrenia and 20 651 ONAP patients between January 2006 and December 2016 in Hong Kong (HK), by estimating all-cause and cause-specific standardized mortality ratios (SMRs), and life-years lost (LYLs), a recently developed, more precise reduced life expectancy measure taking into account the illness onset (age at first-recorded diagnosis). Changes in mortality metrics over the study period were assessed. Study data were retrieved from a territory-wide medical-record database of public healthcare services to 7.5 million HK residents. Results showed that schizophrenia and ONAP patients had higher all-cause (schizophrenia: SMR: 2.49 [95% CI: 2.43-2.55]; ONAP: 2.00 [1.92-2.09]), natural-cause (1.80 [1.74-1.85]; 1.47 [1.40-1.54]), and unnatural-cause (6.97 [6.47-7.49]; 8.53 [7.61-9.52]) mortality rates than general population. Respiratory diseases, cardiovascular diseases, and cancers accounted for the majority of deaths in patient cohorts. Men and women with schizophrenia had 9.53 years and 8.07 years of excess LYLs, respectively. For ONAP, excess LYLs was 8.18 years for men and 5.44 years for women. The overall mortality gap remained similar for both patient groups over time despite their improved longevity and declined unnatural-cause mortality rates. Taken together, schizophrenia and ONAP are associated with increased premature mortality and substantially reduced lifespan in a predominantly Chinese population, with excess deaths mainly attributed to a natural cause. Persistent mortality gap highlights an urgent need for targeted interventions to improve the physical health of patients with psychotic disorders., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ideas of reference (IOR) are often implicated in predicting psychosis onset. They have been conceptualized to present on a continuum, from oversensitive psychological reactions to delusional thoughts. It is however unknown to what extent IOR may be triggered by collective environmental stress. We obtained timely data from 9873 individuals to assess IOR in relation to trauma exposure in the 2019-2020 social unrest in Hong Kong. Two levels of IOR are distinguished: attenuated IOR (IOR-A), being the experience of feeling particularly referred to within a group; and exclusive IOR (IOR-E), the experience of feeling exclusively referred to while others are not. Logistic regressions showed that event-based rumination was a shared predictor for IOR-A (OR = 1.07, CI = 1.03-1.10) and IOR-E (OR = 1.09, CI = 1.02-1.17). For IOR-A, three categories of social unrest-related traumatic events (TEs) were significant predictors, including being attacked or having experienced sexual violence (OR = 4.14, CI = 1.93-8.85), being arrested (OR = 4.48, CI = 1.99-10.10), and being verbally abused (OR = 2.66, CI = 1.28-5.53). Being arrested was significant for IOR-E (OR = 3.87, CI = 1.03-14.52), though not when rumination was included. Education level also significantly predicted IOR-E (OR = 0.72, CI = 0.52-0.99). Further analysis revealed that rumination significantly mediated between TEs and IOR severity (β = 0.26, SE = 0.01, CI = 0.24-0.28). The findings are consistent with the hypothesis that IOR-A and IOR-E occur as levels on a continuum, but each has some distinctive correlates. Extrinsic events may play a more prominent role in IOR-A, while intrinsic factors, such as cognitive capacity, may play a more prominent role in IOR-E. The involvement of rumination across the IOR spectrum suggests an opportunity for intervention., Competing Interests: Declaration of competing interest The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article, all outside of the current submitted work: EYHC has received speaker honoraria from Otsuka and DSK BioPharma, research funding from Otsuka, participated in paid advisory boards for Janssen and DSK BioPharma, and received funding to attend conferences from Otsuka and DSK BioPharma. All other authors declare no competing interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.

Background: Better understanding of interplay among symptoms, cognition and functioning in first-episode psychosis (FEP) is crucial to promoting functional recovery. Network analysis is a promising data-driven approach to elucidating complex interactions among psychopathological variables in psychosis, but has not been applied in FEP., Method: This study employed network analysis to examine inter-relationships among a wide array of variables encompassing psychopathology, premorbid and onset characteristics, cognition, subjective quality-of-life and psychosocial functioning in 323 adult FEP patients in Hong Kong. Graphical Least Absolute Shrinkage and Selection Operator (LASSO) combined with extended Bayesian information criterion (BIC) model selection was used for network construction. Importance of individual nodes in a generated network was quantified by centrality analyses., Results: Our results showed that amotivation played the most central role and had the strongest associations with other variables in the network, as indexed by node strength. Amotivation and diminished expression displayed differential relationships with other nodes, supporting the validity of two-factor negative symptom structure. Psychosocial functioning was most strongly connected with amotivation and was weakly linked to several other variables. Within cognitive domain, digit span demonstrated the highest centrality and was connected with most of the other cognitive variables. Exploratory analysis revealed no significant gender differences in network structure and global strength., Conclusion: Our results suggest the pivotal role of amotivation in psychopathology network of FEP and indicate its critical association with psychosocial functioning. Further research is required to verify the clinical significance of diminished motivation on functional outcome in the early course of psychotic illness.

Ischemic heart disease is the leading cause of mortality in psychotic disorders. There is a paucity of research comprehensively evaluating short-term mortality, cardiovascular complications, and treatment inequality after cardiac events in patients with psychotic disorders. This population-based cohort study examined 30-day and 1-year all-cause mortality, cardiovascular complication rates, 30-day and 1-year receipt of invasive cardiac procedures, and 90-day post-discharge cardioprotective medication treatment following admission for first-recorded acute coronary syndrome (ACS) among patients with psychotic disorders (n = 703) compared with patients without psychotic disorders (n = 66 989) between January 2006 and December 2016 in Hong Kong (HK). Study data were retrieved from territory-wide medical record database of public healthcare services to 7.5 million HK residents. Multivariate regression analyses (ORs and 95% CIs), adjusting for demographics and medical comorbidities, were conducted to evaluate associations between psychotic disorders and post-ACS outcomes. Our results showed that patients with psychotic disorders had higher 30-day (OR: 1.99 [95% CI: 1.65-2.39]) and 1-year (2.13 [1.79-2.54]) mortality, and cardiovascular complication rates (1.20 [1.02-1.41]), lower receipt of cardiac catheterization (30-d: 0.54 [0.43-0.68]; 1-y: 0.46 [0.38-0.56]), percutaneous coronary intervention (30-d: 0.55 [0.44-0.70]; 1-y: 0.52 [0.42-0.63]) and reduced β-blockers (0.81 [0.68-0.97]), statins (0.54 [0.44-0.66]), and clopidogrel prescriptions (0.66 [0.55-0.80]). Associations between psychotic disorder and increased mortality remained significant even after complications and treatment receipt were additionally adjusted. Our findings indicate that psychotic disorders are associated with increased risks of short-term post-ACS mortality, cardiovascular complications, and inferior treatment. Excess mortality is not substantially explained by treatment inequality. Further investigation is warranted to clarify factors for suboptimal cardiac-care and elevated mortality in psychotic disorders to enhance post-ACS outcome., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Evidence shows that schizophrenia is associated with increased incidence of stroke. However, relationship between schizophrenia and short-term mortality risk is understudied, and mixed findings were observed. In this retrospective population-based cohort study, we identified individuals admitted for incident ischemic stroke between 2006 and 2016 using a territory-wide electronic medical record database of public healthcare system in Hong Kong to examine 30-day and 1-year mortality rates in 817 schizophrenia patients compared with 8170 patients without psychotic disorder (10:1 matched to schizophrenia patients on demographics, treatment sites and calendar-period for index admission). Multivariate regression analyses adjusting for medical comorbidities revealed that schizophrenia patients experienced elevated 1-year (16.9% vs 12.1%; p < 0.001) and 30-day mortality (7.2% vs 5.3%; p = 0.053) relative to control group. Additional age- and gender-stratified analyses revealed even more pronounced effect of schizophrenia on raised mortality risk, as indicated by higher odds, in younger-age (<65 years) group and men. Our results indicate that schizophrenia is associated with heightened short-term mortality following incident ischemic stroke. Further research is warranted to identify factors contributing to excess post-stroke deaths among schizophrenia patients to facilitate development of effective interventions for mortality risk reduction., (Copyright © 2019. Published by Elsevier B.V.)

This study examined the epidemiology of trauma exposure (TE) and posttraumatic stress disorder (PTSD) among community-dwelling Chinese adults in Hong Kong. Multistage stratification sampling design was used, and 5,377 participants were included. In Phase 1, TE, probable PTSD (p-PTSD), and psychiatric comorbid conditions were examined. In Phase 2, the Structured Clinical Interview for the DSM-IV (SCID-I) was used to determine the weighted diagnostic prevalence of lifetime full PTSD. Disability level and health service utilization were studied. The findings showed that the weighted prevalence of TE was 64.8%, and increased to 88.7% when indirect TE types were included, with transportation accidents (50.8%) reported as the most common TE. The prevalence of current p-PTSD among participants with TE was 2.9%. Results of logistic regression suggested that nine specific trauma types were significantly associated with p-PTSD; among this group, severe human suffering, sexual assault, unwanted or uncomfortable sexual experience, captivity, and sudden and violent death carried the greatest risks for developing PTSD, odds ratio (OR) = 2.32-2.69. The occurrence of p-PTSD was associated with more mental health burdens, including (a) sixfold higher rates for any past-week common mental disorder, OR = 28.4, (b) more mental health service utilization, p < .001, (c) poorer mental health indexes in level of symptomatology, suicide ideation and functioning, p < .001, and (d) more disability, ps < .001-p = .014. The associations found among TE, PTSD, and health service utilization suggest that both TE and PTSD should be considered public health concerns., (© 2019 International Society for Traumatic Stress Studies.)

Negative symptoms are a key treatment target in early psychosis intervention. There is a paucity of research examining longitudinal course of negative symptoms across the initial years of treatment for first-episode psychosis using individual-based trajectory analysis. No study has been conducted investigating differential relationships of early-stage negative symptom trajectories with long-term distal outcomes. This study examined patterns and baseline predictors of negative symptom trajectories over the first 3 years of treatment in 138 patients aged 18-55 years presenting with first-episode nonaffective psychosis, using latent class growth analysis based on symptom ratings measured at 4 different time points (baseline, 1, 2, and 3 years). We further explored prospective relationships of identified trajectory classes with functional and negative symptom outcomes at 13-year follow-up. Our results revealed 3 distinct negative symptom trajectories including minimal-stable (59.6%), mild-stable (29.4%), and high-increasing (11.0%) trajectories. Poorer premorbid adjustment, more severe global cognitive impairment, and depressive symptoms at baseline were found to predict high-increasing trajectory. Among 3 trajectory classes, patients in high-increasing trajectory had the worst functional and negative symptom outcomes at 13-year follow-up, with post hoc analyses demonstrating significant outcome differences between high-increasing and minimal-stable trajectories. Our findings thus affirm a heterogeneous course of negative symptoms in first-episode psychosis and indicate that early-stage negative symptom trajectories are critically associated with long-term outcomes. Patients displaying persistently high negative symptom levels in the initial 3 years of treatment may represent a specific subgroup who necessitates an extended period of early intervention specifically targeting at negative symptoms to promote early functional recovery., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Functional impairment is prevalent in patients with first-episode psychosis (FEP). Longitudinal course of functioning in the early stage of psychotic illness is under-studied. In this report, we aimed to investigate the patterns and baseline predictors of social-occupational functional trajectories over 3 years, utilizing growth mixture modeling (GMM) analysis, in a large representative Chinese young FEP cohort in Hong Kong., Method: Six hundred seventeen consecutive patients aged 15-25 years presenting with first-episode non-affective psychosis to a specialized early intervention service were studied. Data on demographic, pre-treatment and baseline clinical characteristics were collected. Individual class membership of functioning derived from GMM was based on ratings on Social and Occupational Functioning Scale (SOFAS) measured at five different time-points (baseline, 6, 12, 24 and 36 months) across 3-year follow-up., Results: Four distinct functional trajectories were identified including persistently poor (48.1%, n = 320), early improved (31.3%, n = 203), gradually improved (14.8%, n = 69) and improved-deteriorated (5.8%, n = 25) trajectories. Multinomial regression analysis revealed that male gender, lower educational attainment, a diagnosis of schizophrenia-spectrum disorder and a receipt of inpatient treatment upon initial presentation independently predicted persistently poor trajectory membership., Conclusion: The current study reveals a heterogeneous course of social-occupational functioning in FEP. Our finding that approximately half of the patients displaying persistently poor trajectory over 3 years indicates functional impairment as an unmet therapeutic need in early illness phase. Further research applying individual-based trajectory analysis in FEP is warranted to facilitate better characterization of longitudinal patterns of functioning and development of targeted intervention to promote early recovery., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: This systematic review and meta-analysis aimed to examine the effects of repetitive transcranial magnetic stimulation (rTMS) on cognitive function in older patients with cognitive impairment., Methods: A literature search was performed for articles published in English using the 10 databases (MEDLINE, EMBASE, PsycINFO, INSPEC, the Cumulative Index to Nursing and Allied Health Literature Plus, AMED, Biological Sciences, ClinicalTrials.gov, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews) from their inception to May 2016. The primary outcome was cognitive function as measured by the Mini-Mental State Examination or the Alzheimer's Disease Assessment Scale-cognitive subscale., Results: Seven RCTs were included in the meta-analysis, with a sample of 107 active and 87 sham rTMS. Active rTMS was found to be more effective in improving cognition (Hedges' g = 0.48; 95% confidence interval 0.12 to 0.84)., Conclusions: High-frequency rTMS showed a benefit on cognition amongst older patients with mild to moderate Alzheimer's disease. rTMS was shown to have great potential as a safe and well-tolerated alternative intervention for cognition. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Lifetime prevalence of psychotic disorders varies widely across studies. Epidemiological surveys have rarely examined prevalences of specific psychotic disorders other than schizophrenia, and the majority used a single-phase design without employing clinical reappraisal interview for diagnostic verification. The current study investigated lifetime prevalence, correlates and service utilization of schizophrenia-spectrum, affective, and other non-affective psychotic disorders in a representative sample of community-dwelling Chinese adult population aged 16-75 years (N = 5719) based on a territory-wide, population-based household survey for mental disorders in Hong Kong. The survey adopted a 2-phase design comprising first-phase psychosis screening and second-phase diagnostic verification incorporating clinical information from psychiatrist-administered semi-structured interview and medical record review to ascertain DSM-IV lifetime diagnosis for psychotic disorders. Data on sociodemographics, psychosocial characteristics and service utilization were collected. Our results showed that lifetime prevalence was 2.47% for psychotic disorder overall, 1.25% for schizophrenia, 0.15% for delusional disorder, 0.38% for psychotic disorder not otherwise specified, 0.31% for bipolar disorder with psychosis, and 0.33% for depressive disorder with psychosis. Schizophrenia-spectrum disorder was associated with family history of psychosis, cigarette smoking and variables indicating socioeconomic disadvantage. Victimization experiences were significantly related to affective psychoses and other non-affective psychoses. Around 80% of participants with any psychotic disorder sought some kind of professional help for mental health problems in the past year. Using comprehensive diagnostic assessment involving interview and record data, our results indicate that approximately 2.5% of Chinese adult population had lifetime psychotic disorder which represents a major public health concern., (© The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background Evidence indicates that the positive effects of 2-year early intervention services for psychosis are not maintained after service withdrawal. Optimal duration of early intervention in sustaining initial improved outcomes remains to be determined. Aims To examine the sustainability of the positive effects of an extended, 3-year, early intervention programme for patients with first-episode psychosis (FEP) after transition to standard care. Method A total of 160 patients, who had received a 2-year early intervention programme for FEP, were enrolled to a 12-month randomised-controlled trial (ClinicalTrials.gov: NCT01202357) comparing a 1-year extension of the early intervention (3-year specialised treatment) with step-down care (2-year specialised treatment). Participants were followed up and reassessed 2 and 3 years after inclusion to the trial. Results There were no significant differences between the treatment groups in outcomes on functioning, symptom severity and service use during the post-trial follow-up period. Conclusions The therapeutic benefits achieved by the extended, 3-year early intervention were not sustainable after termination of the specialised service., Competing Interests: Declaration of interestE.Y.H.C has been a member of the paid advisory board for Otsuka, and has received educational grant support from Janssen-Cilag, Eli Lilly, Sanofi-Aventis and Otsuka. E.H.M.L has been a member of the paid advisory boards for Eli Lilly and AstraZeneca., (© The Royal College of Psychiatrists 2017.)