There is growing concern regarding teratogenic effect of antipsychotics. Previous research assessing association between antipsychotics and congenital malformations (CMs) yielded mixed results and were all derived from Western countries. We aimed to examine risk of major and organ/system-specific CMs associated with prenatal antipsychotic exposure in Hong Kong.

This population-based study identified women aged 15–50 years who delivered their first/singleton child between 2003–2018 from public healthcare service database. Propensity score (PS)-weighted logistic-regression analyses were performed to examine risk of CMs following first-trimester exposure to antipsychotic classes (second- and first-generation antipsychotic; SGA and FGA) and six most frequently-prescribed individual antipsychotics.

Of 465,069 women, 419 and 420 redeemed ≥1 prescription of SGA and FGA during first-trimester, respectively. Prevalence of any CMs was 4.9% (95%CI:4.9–5.0%) in unexposed-infants, 9.1% (6.7–12.3%) in SGA-exposed infants, and 6.2% (4.3–9.0%) in FGA-exposed infants. SGA exposure (adjusted-odds-ratio: 2.11 [95%CI:1.19–3.86]) was associated with increased risk of CMs. This finding was consistent with sensitivity analyses addressing exposure misclassification and confounding by treatment indication, but not with PS-matched sensitivity analysis. Elevated risk of CMs was observed in infants exposed to high-dose olanzapine (7.50 [1.65–36.13]) and high-dose quetiapine (15.03 [4.86–56.72]), but with wide-CIs. Organ/system-specific malformations were not associated with SGA, FGA or individual antipsychotics.

We observed a small increased risk of major malformations associated with SGA, but was not consistently affirmed in sensitivity analyses, precluding firm conclusions. Research with large sample size clarifying comparative safety of individual antipsychotics on specific malformations is warranted.

Accumulating studies have assessed mortality risk associated with mood-stabilizers, the mainstay treatment for bipolar disorder (BD). However, existing data were mostly restricted to suicide risk, focused on lithium and valproate and rarely adequately adjusted for potential confounders. This study aimed to assess comparative mortality risk with all, natural and unnatural causes between lithium, valproate and three frequently prescribed second-generation antipsychotics (SGA), with adjustment for important confounders.

This population-based cohort study identified 8137 patients with first-diagnosed BD, who had exposed to lithium (n = 1028), valproate (n = 3580), olanzapine (n = 797), quetiapine (n = 1975) or risperidone (n = 757) between 2002 and 2018. Data were retrieved from territory-wide medical-record database of public healthcare services in Hong Kong. Propensity-score (PS)-weighting method was applied to optimize control for potential confounders including pre-existing chronic physical diseases, substance/alcohol use disorders and other psychotropic medications. PS-weighted Cox proportional-hazards regression was conducted to assess risk of all-, natural- and unnatural-cause mortality related to each mood-stabilizer, compared to lithium. Three sets of sensitivity analyses were conducted by restricting to patients with (i) length of cumulative exposure to specified mood-stabilizer ≥90 days and its medication possession ratio (MPR) ≥90%, (ii) MPR of specified mood-stabilizer ≥80% and MPR of other studied mood-stabilizers <20% and (iii) monotherapy.

Incidence rates of all-cause mortality per 1000 person-years were 5.9 (95% confidence interval [CI]: 4.5–7.6), 8.4 (7.4–9.5), 11.1 (8.3–14.9), 7.4 (6.0–9.2) and 12.0 (9.3–15.6) for lithium-, valproate-, olanzapine-, quetiapine- and risperidone-treated groups, respectively. BD patients treated with olanzapine (PS-weighted hazard ratio = 2.07 [95% CI: 1.33–3.22]) and risperidone (1.66 [1.08–2.55]) had significantly higher all-cause mortality rate than lithium-treated group. Olanzapine was associated with increased risk of natural-cause mortality (3.04 [1.54–6.00]) and risperidone was related to elevated risk of unnatural-cause mortality (3.33 [1.62–6.86]), relative to lithium. The association between olanzapine and increased natural-cause mortality rate was consistently affirmed in sensitivity analyses. Relationship between risperidone and elevated unnatural-cause mortality became non-significant in sensitivity analyses restricted to low MPR in other mood-stabilizers and monotherapy. Valproate- and lithium-treated groups did not show significant differences in all-, natural- or unnatural-cause mortality risk.

Our data showed that olanzapine and risperidone were associated with higher mortality risk than lithium, and further supported the clinical guidelines recommending lithium as the first-line mood-stabilizer for BD. Future research is required to further clarify comparative mortality risk associated with individual SGA agents to facilitate risk-benefit evaluation of alternative mood-stabilizers to minimize avoidable premature mortality in BD.

There is increasing research examining excess mortality in people with bipolar disorder using life expectancy and related measures, which quantify the disease impact on survival. However, there has been no meta-analysis to date summarising existing data on life expectancy in those with bipolar disorder.

To systematically review and quantitatively synthesise estimates of life expectancy and years of potential life lost (YPLL) in people with bipolar disorder.

We searched Embase, Medline, PsycINFO and Web of Science databases up to 31 March 2021. We generated pooled life expectancy using random-effects models, and derived YPLL summary estimate by calculating averaged values weighted by sample size of individual studies. Subgroup analyses were conducted for gender, geographical region, study period, a given age (set-age) for lifespan estimation and causes of death. The study was registered with PROSPERO (CRD42021241705).

Eleven and 13 studies were included in the review for life expectancy (n = 96 601) and YPLL (n = 128 989), respectively. Pooled life expectancy was 66.88 years (95% CI 64.47–69.28; I2 = 99.9%, P < 0.001), was higher in women than men (70.51 (95% CI 68.61–72.41) v. 64.59 (95% CI 61.16–68.03); z = 2.00, P = 0.003) and was lowest in Africa. Weighted average YPLL was 12.89 years (95% CI 12.72–13.07), and was greatest in Africa. More YPLL was observed when lifespan was estimated at birth than at other set-age. YPLLs attributable to natural and unnatural deaths were 5.94 years (95% CI 5.81–6.07) and 5.69 years (95% CI 5.59–5.79), respectively.

Bipolar disorder is associated with substantially shortened life expectancy. Implementation of multilevel, targeted interventions is urgently needed to reduce this mortality gap.

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.

We investigated whether schizophrenia increased the risk of overall mortality, complications and post-complication mortality in people with diabetes.

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.

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.

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.

To assess the association of diagnostic predictors available in the emergency department (ED) with the outcome diagnosis of severe acute respiratory syndrome (SARS).

This retrospective cohort study describes all patients from the Amoy Garden complex who presented to an ED SARS screening clinic during a 2-month outbreak. Clinical and diagnostic predictors were recorded, along with ED diagnoses. Final diagnoses were established independently based on diagnostic tests performed after the ED visit. Associations of key predictors with the final diagnosis of SARS were described.

Of 821 patients, 205 had confirmed SARS, 35 undetermined SARS and 581 non-SARS. Multivariable logistic regression showed that the strongest predictors of SARS were abnormal chest x-ray (odds ratio [OR] = 17.4), subjective fever (OR = 9.7), temperature >38°C (OR = 6.4), myalgias (OR = 5.5), chills and rigors (OR = 4.0) and contact exposure (OR = 2.6). In a subset of 176 patients who had a complete blood cell count performed, the strongest predictors were temperature ≥38ºC (OR = 15.5), lymphocyte count <1000 (OR = 9.3) and abnormal chest x-ray (OR = 5.7). Diarrhea was a powerful negative predictor (OR = 0.03) of SARS.

Two components of the World Health Organization case definition — fever and contact exposure — are helpful for ED decision-making, but respiratory symptoms do not discriminate well between SARS and non-SARS. Emergency physicians should consider the presence of diarrhea, chest x-ray findings, the absolute lymphocyte count and the platelet count as significant modifiers of disease likelihood. Prospective validation of these findings in other clinical settings is desirable.

To compare the diagnostic accuracy of emergency department (ED) physicians with the World Health Organization (WHO) case definition in a large community-based SARS (severe acute respiratory syndrome) cohort.

This was a cohort study of all patients from Hong Kong’s Amoy Garden complex who presented to an ED SARS screening clinic during a 2-month outbreak. Clinical findings and WHO case definition criteria were recorded, along with ED diagnoses. Final diagnoses were established independently based on relevant diagnostic tests performed after the ED visit. Emergency physician diagnostic accuracy was compared with that of the WHO SARS case definition. Sensitivity, specificity, predictive values and likelihood ratios were calculated using standard formulae.

During the study period, 818 patients presented with SARS-like symptoms, including 205 confirmed SARS, 35 undetermined SARS and 578 non-SARS. Sensitivity, specificity and accuracy were 91%, 96% and 94% for ED clinical diagnosis, versus 42%, 86% and 75% for the WHO case definition. Positive likelihood ratios (LR+) were 21.1 for physician judgement and 3.1 for the WHO criteria. Negative likelihood ratios (LR–) were 0.10 for physician judgement and 0.67 for the WHO criteria, indicating that clinician judgement was a much more powerful predictor than the WHO criteria.

Physician clinical judgement was more accurate than the WHO case definition. Reliance on the WHO case definition as a SARS screening tool may lead to an unacceptable rate of misdiagnosis. The SARS case definition must be revised if it is to be used as a screening tool in emergency departments and primary care settings.