Association between the mood stabilizing treatment of bipolar disorder and risk of suicide attempts: A self-controlled case series study.

Bipolar disorder (BPD) is associated with high rates of suicide attempts but the anti-suicidal effect of mood stabilizing agents remains unclear. This study aimed to examine the association between mood stabilizing agents (lithium, valproate, lamotrigine, carbamazepine or antipsychotics) and risk of suicide attempts in patients with BPD using self-controlled case series study design. Among 14,087 patients with BPD who received mood stabilizing agents from 2001 to 2020 in Hong Kong, 1316 patients had at least one suicide attempts during the observation period. An increased risk of suicide attempts was observed 14 days before treatment initiation compared to non-exposed period. Following treatment initiation, an increased risk with smaller magnitude was found with the use of mood stabilizing agents. A lower risk was observed with lithium and antiepileptics while the risk remained attenuated with decreasing magnitude with antipsychotics. During 30-day post-treatment period, the risk was elevated. Therefore, this study suggests that use of mood stabilizing agents is not causally associated with an increased risk of suicide attempts. Indeed, there are potential protective effects of lithium and antiepileptics against suicide attempts. Assiduous monitoring of symptoms relapse and warning signs of suicide should be part of the management plan and discussed between clinicians, caregivers and patients.

Association between the pharmacological treatment of bipolar disorder and risk of traumatic injuries: a self-controlled case series study.

BACKGROUND: Patients with bipolar disorder (BPD) are prone to engage in risk-taking behaviours and self-harm, contributing to higher risk of traumatic injuries requiring medical attention at the emergency room (ER).We hypothesize that pharmacological treatment of BPD could reduce the risk of traumatic injuries by alleviating symptoms but evidence remains unclear. This study aimed to examine the association between pharmacological treatment and the risk of ER admissions due to traumatic injuries. METHODS: Individuals with BPD who received mood stabilizers and/or antipsychotics were identified using a population-based electronic healthcare records database in Hong Kong (2001-2019). A self-controlled case series design was applied to control for time-invariant confounders. RESULTS: A total of 5040 out of 14 021 adults with BPD who received pharmacological treatment and had incident ER admissions due to traumatic injuries from 2001 to 2019 were included. An increased risk of traumatic injuries was found 30 days before treatment [incidence rate ratio (IRR) 4.44 (3.71-5.31), p < 0.0001]. After treatment initiation, the risk remained increased with a smaller magnitude, before returning to baseline [IRR 0.97 (0.88-1.06), p = 0.50] during maintenance treatment. The direct comparison of the risk during treatment to that before and after treatment showed a significant decrease. After treatment cessation, the risk was increased [IRR 1.34 (1.09-1.66), p = 0.006]. CONCLUSIONS: This study supports the hypothesis that pharmacological treatment of BPD was associated with a lower risk of ER admissions due to traumatic injuries but an increased risk after treatment cessation. Close monitoring of symptoms relapse is recommended to clinicians and patients if treatment cessation is warranted.

Association between statins and the risk of suicide attempt, depression, anxiety, and seizure: A population-based, self-controlled case series study.

BACKGROUND: Risk of suicide attempt, depression, anxiety and seizure and the association with statins is an ongoing debate. We aim to investigate the association between statins and the above neuropsychological outcomes, in specific pre- and post-exposure time windows. METHODS: We identified patients aged 40-75 years old who were dispensed a statin between January 1, 2003 and December 31, 2012 from the Hong Kong Clinical Data Analysis & Reporting System (CDARS), an electronic medical records database. Patients with new onset of suicide attempt, depression, anxiety and seizure were derived from the original dataset separately, in a self-controlled case series study design. A non-parametric spline-based self-controlled case series model was built to measure continuous changes of risk. RESULTS: We identified 396,614 statin users. The risk of each outcome was elevated prior to statin initiation with incidence rate ratios of 1.38 (95 % CI, 1.09-1.74) for suicide attempt, 1.29 (95 % CI, 1.15-1.45) for depression, 1.35 (95 % CI, 1.19-1.53) for anxiety, and 1.45 (95 % CI, 1.21-1.73) for seizure. The incidence rate ratios remained elevated after the initiation of statins during the first 90 and 91-365 days after statin prescription and decreased to the baseline level after 1 year of continuous prescription. LIMITATIONS: CDARS includes prescription data but not adherence data, which could lead to misclassification of exposure periods. CONCLUSIONS: Our study does not support a direct association between statin use and suicide attempt, depression, anxiety and seizure, whose risks could be explained by cardiovascular events, for which statins were prescribed.

Bipolar disorder prevalence and psychotropic medication utilisation in Hong Kong and the United Kingdom.

PURPOSE: Bipolar disorder (BPD) is often an under-addressed mental disorder. Limited studies have investigated its epidemiology and drug utilisation in Hong Kong (HK) and the United Kingdom (UK) and thus local prescribing practices remain unclear. This study aimed to determine the prevalence of BPD and the prescribing of psychotropic medications as maintenance treatment from 2001-2018 in HK and the UK. METHOD: A retrospective study using the data from Clinical Data Analysis and Reporting System in HK and IQVIA Medical Research Data in the UK. RESULTS: The prevalence of BPD diagnosis in HK and the UK more than doubled during the study period. Some distinct changes in prescribing patterns over time were observed. Lithium use declined by 2.46% and 14.58% in HK and the UK, respectively. By 2018, patients were 4.6 times more likely to receive antidepressant monotherapy in the UK versus HK (15.62% vs. 3.42%). In HK, 38.41% of women of childbearing age were prescribed valproate in 2018 compared with 8.46% in the UK. CONCLUSION: The prevalence of BPD diagnosis has been increasing in HK and the UK. The disparity in prescribing patterns of BPD maintenance treatment in two regions reflected three major issues in clinical practice: (1) under-prescribing of lithium in both regions, (2) antidepressant monotherapy in the UK and (3) overprescribing of valproate to women of childbearing age in HK. A review of current clinical treatment guidelines and regulations of prescribing practice by local clinicians should be immediately implemented to ensure the safe use of medications in patients with BPD.

Understanding the barriers to using oral anticoagulants among long-term aspirin users with atrial fibrillation - a qualitative study.

BACKGROUND: Despite international treatment guidelines currently advocating oral anticoagulants (OACs) as the only appropriate stroke prevention therapy for patients with atrial fibrillation (AF) and evidence that OACs can greatly reduce the risk of stroke with similar risk of bleeding compared with aspirin, the underuse of OACs in patients with AF is common globally, especially in Asia. This study aimed to identify the barriers to prescribing and using OACs among long-term aspirin users with AF. METHOD: Face-to-face interviews were conducted with fourteen eligible patients with AF using a semi-structured interview guide. The interview recordings were transcribed verbatim and data was analyzed according to the principles of thematic analysis. RESULTS: Five themes were developed: awareness of AF symptoms and diagnosis; knowledge and understanding of AF and stroke prevention therapy; role of decision-making in prescribing; willingness to switch from aspirin to OACs; and impact of OAC regimen on daily living. The majority of the patients were not aware of the symptoms and diagnosis of AF and only had a vague understanding of the illness and stroke prevention therapy, leading to their minimal involvement in decisions relating to their treatment. Some patients and their caregivers were particularly concerned about the bleeding complications from OACs and perceived aspirin to be a suitable alternative as they find the adverse effects from aspirin manageable and so preferred to remain on aspirin if switching to OACs was not compulsory. Lastly, the lifestyle modifications required when using warfarin, e.g. alternative dosing regimen, diet restriction, were seen as barriers to some patients and caregivers. CONCLUSION: The findings revealed patients' knowledge gap in AF management which may be targeted using educational interventions to improve patients' understanding of AF and its management and hence encourage active participation in the decision-making of their treatment in the future.

Comparative Outcomes Between Direct Oral Anticoagulants, Warfarin, and Antiplatelet Monotherapy Among Chinese Patients with Atrial Fibrillation: A Population-Based Cohort Study.

INTRODUCTION: Outcomes associated with suboptimal use of antithrombotic treatments (antiplatelets, warfarin, direct oral anticoagulants [DOACs]) are unclear in Chinese patients with atrial fibrillation (AF). OBJECTIVES: Our objective was to assess the prescription patterns, quality, effectiveness, and safety of antithrombotic treatments. METHODS: This was a population-based cohort study using electronic health records in Hong Kong. Patients newly diagnosed with AF during 2010-2016 were followed up until 2017. Patients at high stroke risk (CHA2DS2-VASc score ≥ 2) and receiving antithrombotic treatments were matched using propensity scoring. We used Cox proportional hazards regression to compare the risks of ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between groups. RESULTS: Of the 52,178 high-risk patients with AF, 27,614 (52.9%) received antithrombotic treatment and were included in the analyses. Between 2010 and 2016, prescribing of antiplatelets and warfarin declined and that of DOACs increased dramatically (from 1 to 32%). Two-thirds of warfarin users experienced poor anticoagulation control. Warfarin and DOACs were associated with lower risks of ischemic stroke (warfarin, hazard ratio [HR] 0.51 [95% confidence interval (CI) 0.36-0.71]; DOACs, HR 0.69 [95% CI 0.51-0.94]) and all-cause mortality (warfarin, HR 0.47 [95% CI 0.39-0.57]; DOACs, HR 0.45 [95% CI 0.37-0.55]) than were antiplatelets. DOACs were associated with a lower risk of ICH than was warfarin (HR 0.53 [95% CI 0.34-0.83]). GIB risks were similar among all groups. CONCLUSION: Antiplatelet prescribing and suboptimal warfarin management remain common in Chinese patients with AF at high risk of stroke. DOAC use may be associated with a lower risk of ischemic stroke and all-cause mortality when compared with antiplatelets and with a lower risk of ICH when compared with warfarin.

Evaluation of functional and malignant adrenal incidentalomas.

BACKGROUND: Adrenal incidentalomas are adrenal masses discovered inadvertently. We undertook this study to review the clinical characteristics of patients with adrenal incidentalomas who presented to a tertiary endocrine center in Hong Kong. METHODS: Retrospective review of all 139 cases of adrenal incidentalomas that were referred to the Endocrine Centre of the Prince of Wales Hospital between June 1, 2000, and May 31, 2007. We reviewed detailed patient history, physical examination findings, and symptoms and signs related to hormonal hypersecretion or malignant neoplasm and recorded clinical indications for performing diagnostic radiological imaging. RESULTS: Sixty-one patients (43.9%) had nonfunctional benign adrenal adenomas, 52 (37.4%) had functional lesions, 15 (10.8%) had malignant adrenal lesions, and the remaining 11 (7.9%) had varying adrenal disease. Among those with functional lesions, 27 (19.4%) had lesions that secreted excess cortisol; 12 (8.6%), lesions that secreted aldosterone; 12 (8.6%), lesions that secreted excess catecholamines; and 1 (0.7%), a lesion that demonstrated excess secretion of cortisol and aldosterone. Only 5 of the 27 patients with cortisol-secreting adrenal incidentalomas had symptoms or signs of excess cortisol levels at presentation. CONCLUSIONS: Adrenal incidentaloma is a commonly encountered clinical problem. Functional or primary malignant adrenal incidentalomas can be detected at an earlier stage during hormonal and radiological evaluations, which provides an opportunity for further management.

Use of sulphonylurea and cancer in type 2 diabetes-The Hong Kong Diabetes Registry.

BACKGROUND: Hyperglycaemia is a risk factor for cancer and some sulphonylureas have anti-oxidant properties. This study examined associations between use of sulphonylureas and cancer. METHODS: A consecutive cohort of 6103 Hong Kong Chinese patients with T2DM, free of cancer, was analysed using Cox models. Sulphonylurea usage was defined as use of the drugs at or within 2.5 years before enrolment and/or during follow-up periods. We adjusted for identified risk factors of cancer, use of other drugs, non-linear associations of lipids with cancer and probabilities of use of these drugs at different times and doses where appropriate. RESULTS: During a median of 4.91 years of follow-up, 271 developed cancer. Glibenclamide, gliclazide and glipizide were ever used in 32.5% (n = 1983), 47.8% (n = 2920) and 13.5% (n = 823). After adjustment for covariates, use of gliclazide and glibenclamide was associated with reduced cancer risk in a dose-dependent manner. In addition, there were interactions between metformin and glibenclamide/glipizide use towards lower adjusted cancer risks. CONCLUSIONS: In T2DM, use of glibenclamide and gliclazide may be associated with reduced cancer risk.

BMI and waist circumference in predicting cardiovascular risk factor clustering in Chinese adolescents.

OBJECTIVE: To derive the optimal BMI and waist circumference (WC) cut-off values to predict clustering of cardiovascular risk factors in Hong Kong Chinese adolescents. RESEARCH METHODS AND PROCEDURES: A total of 2102 Hong Kong Chinese 12 to 19 years of age were recruited. Participants were considered to have clustering of risk factors if at least three of the following risk factors were present: 1) high-density lipoprotein cholesterol (HDL-C) < or = 1.03 mM, 2) low-density lipoprotein cholesterol (LDL-C) > or = 2.6 mM, 3) triglyceride (TG) > or = 1.24 mM, 4) fasting plasma glucose (FPG) >/=6.1 mM, and 5) age-, sex-, and height-adjusted systolic or diastolic blood pressure (BP) > or = 90th percentile. Receiver operating characteristics (ROC) curves were generated to identify the optimal age-adjusted BMI and WC cut-off values to predict clustering of risk factors in boys and girls separately. These age-adjusted BMI and WC cut-offs were transformed to percentile values. Cole's lambda-mu-sigma (LMS) method was used to obtain smoothed age-specific BMI and WC at these percentile values. RESULTS: The areas under ROC curves for BMI in girls and boys were 0.85 [95% confidence interval (CI), 0.77 to 0.92] and 0.76 (95% CI, 0.66 to 0.85), respectively. The respective areas under ROC curves for WC in girls and boys were 0.82 (95% CI, 0.74 to 0.91) and 0.78 (95% CI, 0.68 to 0.87). The optimal BMI thresholds were at the 78th percentile for girls and the 72nd percentile for boys. The respective values for WC were at the 77th percentile for girls and the 76th percentile for boys. The sensitivities and specificities of these cut-off values ranged from 72% to 80%. DISCUSSION: Age- and sex-specific BMI and WC cut-off values can be used to identify adolescents with clustering of cardiovascular risk factors.

Effects of treatment targets on subsequent cardiovascular events in Chinese patients with type 2 diabetes.

OBJECTIVE: International guidelines recommend optimal control of risk factors in diabetes to prevent cardiovascular events. We examined risk associations between achieving treatment targets for glycemia, blood pressure and lipid control, and other risk factors on subsequent cardiovascular events in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Between 1995 and 2005, 6,386 Chinese type 2 diabetic patients without a history of coronary heart disease (CHD) or stroke were recruited. They were classified according to the number of treatment targets attained at baseline, and their cardiovascular outcomes were compared. Treatment targets were defined as A1C <7.0%, blood pressure <130/80 mmHg, and LDL cholesterol <2.6 mmol/l. RESULTS: After a median follow-up of 5.7 years, cumulative incidence of CHD or stroke (n = 749) increased with decreasing numbers of treatment targets attained at baseline. Attainment of two or more targets at baseline was associated with reduced risk of CHD compared with those with no target achieved (hazard ratio 0.69 [95% CI 0.50-0.94], P = 0.020). However, the association lost its significance after adjustment for urinary albumin-to-creatinine ratio, estimated glomerular filtration rate, and hemoglobin. CONCLUSIONS: Reaching more treatment targets was associated with reduced risk of new onset of CHD in Chinese patients with type 2 diabetes.