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Background: Atherosclerosis accounts for cardiovascular diseases (CVDs). This study aimed to explore the association between carotid intima-media thickness (CIMT), psycho-pharmacotherapy, and inflammatory markers along with other molecules related to atherosclerosis in bipolar disorder (BD).Methods: The euthymic patients with bipolar I disorder (BD-I) aged over 20 years were recruited to measure CIMT through ultrasound and the blood levels of lipid profiles, soluble tumor necrosis factor receptor-1 (sTNF-R1), soluble interleukin-6 receptor (sIL-6R), monocyte chemoattractant protein-1, chitinase 3-like 1, endothelial adhesive proteins, and thrombin-antithrombin complex.Results: Participants were 103 BD-I patients with mean 44.3 years old. The ratio of lithium exposure in relation to illness chronicity and the current daily dosage of lithium therapy exhibited an inverse relationship with CIMT in the entire sample. After controlling for age and BMI, multivariate regression indicated that a higher lithium level was significantly associated with decreased CIMT in the entire sample, high-risk (those with CVDs or endocrine diseases, N = 48), middle-risk (those without CVDs and endocrine diseases, N = 55), and low-risk (those aged <45 years in the middle-risk subgroup, N = 43) subgroups. Furthermore, higher levels of sTNF-R1 in the entire sample and high-risk subgroup and sIL-6R in the middle- and low-risk subgroups were statistically associated with greater CIMT.Limitation: The age range was too wide to control for the effect of age on CIMT and medication.Conclusions: Lithium exposure may be a protective factor for atherosclerosis progression in BD-I. The chronic inflammation in BD-I with activated macrophages and monocytes may link with the atherosclerosis development over time. [ABSTRACT FROM AUTHOR]

Background: Many studies have used Taiwan's National Health Insurance Research database (NHIRD) to conduct psychiatric research. However, the accuracy of the diagnostic codes for psychiatric disorders in NHIRD is not validated, and the symptom profiles are not available either. This study aimed to evaluate the accuracy of diagnostic codes and use text mining to extract symptom profile and functional impairment from electronic health records (EHRs) to overcome the above research limitations.Methods: A total of 500 discharge notes were randomly selected from a medical center's database. Three annotators reviewed the notes to establish gold standards. The accuracy of diagnostic codes for major psychiatric illness was evaluated. Text mining approaches were applied to extract depressive symptoms and function profiles and to identify patients with major depressive disorder.Results: The accuracy of the diagnostic code for major depressive disorder, schizophrenia, and dementia was acceptable but that of bipolar disorder and minor depression was less satisfactory. The performance of text mining approach to recognize depressive symptoms is satisfactory; however, the recall for functional impairment is lower resulting in lower F-scores of 0.774-0.753. Using the text mining approach to identify major depressive disorder, the recall was 0.85 but precision was only 0.69.Conclusions: The accuracy of the diagnostic code for major depressive disorder in discharge notes was generally acceptable. This finding supports the utilization of psychiatric diagnoses in claims databases. The application of text mining to EHRs might help in overcoming current limitations in research using claims databases. [ABSTRACT FROM AUTHOR]

Purpose: Excessive mortality has been seen in patients with personality disorder (PD), but it has not been well-studied when patients also have other psychiatric comorbidities. This study investigated the mortality rates and causes of death in an Asian cohort with PD.Method: We enrolled patients ≥ 18 years of age with PD as defined by DSM-IV criteria (N = 1172), who had been admitted to a psychiatric service center in northern Taiwan between 1985 and 2008. By linking with the national mortality database (1985-2008), cases of mortality (n = 156, 13.3%) were obtained. We calculated the standardized mortality ratios (SMRs) to estimate the mortality gap between patients with PD and the general population. Stratified analyses of mortality rates by Axis I psychiatric comorbidity and sex were performed.Results: Borderline PD (n = 391, 33.4%) was the dominant disorder among the subjects. The SMRs for all-cause mortality of PD alone, PD comorbid with non-substance use disorder(non-SUD), and PD comorbid with SUD were 4.46 (95% CI 1.94-6.98), 7.42 (5.99-8.85), and 15.96 (11.07-20.85), respectively. Among the causes of death, the SMR for suicide was the highest (46.92, 95% CI 34.29-59.56). The SMR for suicide in PD patients with comorbid SUD was unusually high (74.23, 95% CI 33.88-114.58). Women had a significant increase in suicide with an SMR of 59.00 (95% CI 37.89-80.11). Men had significant increase in SMRs for cardiovascular disease and gastrointestinal disease.Conclusions: We found significant synergistic effects of PD and SUD on mortality risk. A personality assessment should be mandatory in all clinical settings to prevent premature death and detect SUD early. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper was to analyze medical utilization patterns of female patients with anorexia nervosa before their first inpatient care visit for anorexia nervosa using the National Health Insurance Research Database (NHIRD) of Taiwan.Method: We selected female anorexia nervosa patients (n=239) and control participants hospitalized for peptic ulcers (n=478) or appendectomy (n=478) who were matched by age and incident year from two subsets of the NHIRD. The number of visits, specialists, diagnosis distribution, and selected procedures used in ambulatory services during the 2-year period before the index admission were identified and compared. Healthcare service expenditures were also analyzed.Results: Compared to the control groups, the female anorexia nervosa patients used more outpatient services (anorexia nervosa, 58.6±45.0 visits; peptic ulcers, 45.3±37.3 visits; appendectomy, 32.5±26.0 visits), mainly due to psychiatric visits. Anorexia nervosa patients were more likely to have received a diagnosis of digestive, endocrine/metabolic, and mental disorders than patients in the control groups. Although nearly equal percentages of patients in the three groups had obtained a diagnosis of a digestive disease, anorexia nervosa patients received digestive disease diagnoses with greater frequency.Conclusions: We posit that the various physical symptoms of anorexia nervosa patients and physicians' low level of suspicion of anorexia nervosa led to delayed diagnoses and greater medical utilization than that of the controls groups. Education to raise awareness of anorexia nervosa and other eating disorders among physicians is warranted. [ABSTRACT FROM AUTHOR]

Background: The association between smoking and suicide is still controversial, particular for early life cigarette smoking exposure. Few studies have investigated this association in adolescents using population-based cohorts, and the relationship with second hand smoking (SHS) exposure has not been addressed. Methods and Findings: In this study, we followed a large population-based sample of younger people to investigate the association between smoking, SHS exposure and suicide mortality. Between October 1995 and June 1996, 162,682 junior high school students ages 11 to 16 years old living in a geographic catchment area in Taiwan were enrolled and then followed till December 2007 (1,948,432 person-years) through linkage to the National Death Certification System. Participants who were currently smoking at baseline had a greater than six-fold higher suicide mortality than those who did not smoke (29.5 vs. 4.8 per 100,000 person-years, p<0.001) as well as higher natural mortality (33.7 vs. 10.3 per 100,000 person-years, p<0.001). After controlling for gender, age, parental education, asthma, allergic rhinitis, and alcohol consumption, the adjusted hazard ratios for suicide were 3.69 (95% CI 1.85-7.39) in current smokers, and 1.47 (95% CI 0.94-2.30) and 2.83 (95% CI 1.54-5.20) respectively in adolescents exposed to SHS of 1-20 cigarettes and >20 cigarettes/per day. The estimated depression-adjusted odds ratio did not change substantially. The population attributable fractions for suicide associated with smoking and heavy SHS exposure (>20 cigarettes/per day) were 9.6% and 10.6%, respectively. Conclusions: This study showed evidence of excess suicide mortality among young adults exposed to active or passive early life cigarette smoking. [ABSTRACT FROM AUTHOR]

Introduction and Aims. Methamphetamine use leads to increased likelihood of premature death. The authors investigated the causes of death and risk of mortality in a large cohort of patients with methamphetamine dependence. Design and Methods. A cohort of 1254 subjects with methamphetamine dependence, admitted to a psychiatric centre in Taiwan from January 1990 to December 2007, was retrospectively studied. Diagnostic and sociodemographic data for each subject were extracted from the medical records based on a chart review process. Mortality data were obtained by linking to the National Death Certification System and standardised mortality ratios (SMRs) were estimated. The risk and protective factors for all-cause deaths were explored by means of survival analyses. Results. During the study period, 130 patients died. Of them, 63.1% died unnatural deaths, while the remaining 36.9% died natural deaths. The 1 year cumulative rates for unnatural and natural deaths were 0.018 and 0.006, respectively, and the 5 year rates were 0.046 and 0.023, respectively. The cohort had excessive mortality (SMR = 6.02), and women had a higher SMR for unnatural deaths than men (26.19 vs. 9.82, P = 0.001). For all-cause deaths, comorbidity with other substance use disorders was associated with increased risk of death, despite that being married was associated with a reduced risk. Discussion and Conclusions. A substantial proportion of the deceased died natural deaths, but most died unnatural deaths. The findings show significant evidence to provide valuable insight into premature deaths among methamphetamine-dependent users. This information is valuable for development of prevention and intervention programs.[Kuo C-J, Liao Y-T, Chen WJ, Tsai S-Y, Lin S-K, Chen C-C. Causes of death of patients with methamphetamine dependence: A record-linkage study. Drug Alcohol Rev 2010;30:621-628] [ABSTRACT FROM AUTHOR]

Aims. The causes of death among a series of patients with substance dependence were investigated. Setting. A psychiatric teaching hospital in Taipei, Taiwan (Taipei City Psychiatric Center). Participants. A total of 1698 patients with various diagnostic categories of substance dependence, who had been admitted to TCPC for detoxification were followed-up from 1985 to 1996. Design. A record-linkage study was performed using the patient's national identification number to link between TCPC chart records and the mortality file compiled by the National Department of Health. Risk factor analyses for mortality included socio-demographic data, clinical diagnosis and cause of death. Findings. A total of 141 patients died during the study period. Among them, 83 had a diagnosis of alcohol dependence, 41 of heroin dependence and the remaining 17 cases of sedative, glue or hallucinogen dependence. The annual mortality rate of patients with heroin dependence was 1.94%. Accidental death is the leading cause of death among patients with heroin dependence. However, the patients with alcohol dependence had a higher mortality risk than those with heroin dependence (relative hazard = 1.91, p < 0.001) in this study. The proportion of non-violent death was significantly higher among the patients with alcohol dependence than those with heroin dependence (p < 0.005). Conclusion. The causes of death among patients with substance dependence found in this Taiwanese series were very similar to those reported in the western literature. However, differences included the absence of death among heroin addicts due to HIV-related disease and a markedly high percentage of alcoholic patients who died of liver diseases. [ABSTRACT FROM AUTHOR]

Clozapine is indicated as the last-line agent for the treatment of refractory schizophrenia due to its side effects. This study included an Asian schizophrenia population and investigated the effect of clozapine on the risks of all-cause, natural, and suicide mortality. This study included a large-scale schizophrenia inpatient cohort derived from the National Health Insurance Research Database from January 1, 2001, to December 31, 2019 (n = 43,025). Of them, we selected those who received clozapine (clozapine cohort, n = 5800). From those who never used clozapine, we selected two individuals for each patient in the clozapine cohort by matching by age, sex, and the year of the index date (ratio: 1:2, control cohort, n = 11,583). The clozapine and nonclozapine control cohorts together were defined as the study cohort (n = 17,383). Multivariate Cox proportional-hazards regression with a time-dependent model was performed to investigate the effect of individual antipsychotic agents on mortality. All individual first-generation antipsychotics were not associated with mortality risk. However, most individual second-generation antipsychotics exerted protective effects against all-cause and natural mortality. Furthermore, only clozapine and risperidone were significantly associated with a low risk of suicide mortality. Only clozapine exhibited a dose-dependent relationship with all-cause, natural, and suicide mortality. This study provides robust evidence supporting the strong protective effect of clozapine on all-cause, suicide, and natural mortality risks in an Asian population. Under close monitoring, clozapine use can be advantageous in patients with schizophrenia who are at a high risk of suicide. [ABSTRACT FROM AUTHOR]

A review of the article "Rates, Characteristics and Circumstances of Methamphetamine-related Death in Australia: A National 7-year Study" by D. Darke, S. Kaye, and J. Duflou, which appears in a 2017 issue of the journal, is presented.

Background: Bipolar disorder (BD) is a severe mental disorder related to neurocognitive deficits. Exposure to childhood trauma is associated with worse cognitive performance. Different compositions of childhood trauma in BD and their impacts on cognition are rarely reported. Methods: We used the Brief Assessment of Cognition in Affective Disorders (BAC-A) to assess cognitive performance and the Chinese version of the Short Form of the Childhood Trauma Questionnaire (C-CTQ-SF) to assess childhood trauma experience among 55 euthymic BD patients. Cluster analysis was applied to dissect their childhood trauma experiences, which revealed three distinct clusters: a low trauma group, neglect-focus group, and multiple-trauma-experience group. We compared the cognitive function between the three clusters and used a generalized linear model to evaluate the impact of childhood neglect on cognitive domains. Results: The neglect-focus cluster showed prominent exposures to physical and emotional neglect (41.8%). BD patients in this cluster performed worse in BAC-A compared with patients in the multiple trauma cluster, especially in working memory and processing speed. The neglect-focus group revealed a significant negative effect on the composite score (ß = -0.904, p = 0.025) and working memory (ß = -1.150, p = 0.002) after adjusting sex, age, education year, BMI and total psychotropic defined daily dose. Conclusions: Distinct patterns of childhood trauma experience are seen in BD patients and are related with different cognitive profiles. Early exposure of neglect-focus trauma was associated with the worst cognitive performance in current study. Further studies investigating the intensity of the neglect, as well as individual resilience and coping mechanisms in BD, are warranted. [ABSTRACT FROM AUTHOR]

Background: Examining patients with first-episode psychosis (FEP) provides opportunities to better understand the mechanism underlying these illnesses. By incorporating quantitative measures in FEP patients, we aimed to (1) determine the baseline distribution of clinical features; (2) examine the impairment magnitude of the quantitative measures by comparing with external controls and then the counterparts of schizophrenia patients of different familial loadings; and (3) evaluate whether these quantitative measures were associated with the baseline clinical features. Methods: Patients with FEP were recruited from one medical center, two regional psychiatric centers, and two private clinics in northern Taiwan with clinical features rated using the Positive and Negative Syndrome Scale (PANSS) and Personal and Social Performance (PSP) scale. Quantitative measurements included the Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), niacin response abnormality (NRA), and minor physical anomalies and craniofacial features (MPAs). To evaluate the relative performance of the quantitative measures in our FEP patients, four external comparison groups from previous studies were used, including three independent healthy controls for the CPT, WCST, and NRA, respectively, and one group of treatment-resistant schizophrenia patients for the MPAs. Additionally, patients from simplex families and patients from multiplex families were used to assess the magnitude of FEP patients’ impairment on the CPT, WCST, and NRA. Results: Among the 80 patients with FEP recruited in this study (58% female, mean age = 25.6 years, mean duration of untreated psychosis = 132 days), the clinical severity was mild to moderate (mean PANSS score = 67.3; mean PSP score = 61.8). Patients exhibited both neurocognitive and niacin response impairments (mean Z-scores: −1.24 for NRA, − 1.06 for undegraded d', − 0.70 for degraded d', − 0.32 for categories achieved, and 0.44 for perseverative errors) but did not show MPAs indicative of treatment resistance. Among these quantitative measures, three of the four neurocognitive indices were correlated with the baseline clinical features, whereas NRA did not show such correlation. Conclusions: This FEP study of Taiwanese patients revealed the presence of neurocognitive performance and niacin response and their different relationships with clinical features, rendering this sample useful for future follow-up and incorporation of multiomics investigation. [ABSTRACT FROM AUTHOR]

People with schizophrenia are at a greater risk of poor physical health than the general population. This study investigated the annual incidence of physical illnesses after a new schizophrenia diagnosis, which has rarely been investigated in the literature. The authors collected data from Taiwan's National Health Insurance Research Database from January 1, 1996, to December 31, 2013, and enrolled 1910 patients with newly diagnosed schizophrenia cases aged 10–40 years and 7640 age- and sex-matched controls from the general population. They estimated the 1-year prevalence and annual incidence rate ratio (IRR) of specified physical diseases across 3 years in the schizophrenia group compared with the controls. Several physical illnesses were prevalent within 1 year of schizophrenia diagnosis. Regarding incident physical illnesses, patients had a moderate to strong risk of numerous physical illnesses (IRR > 3.0: ischemic heart disease, cerebrovascular disease, diabetes mellitus, and cancer; IRR 1.8–3.0: other forms of heart disease, vein and lymphatic diseases, pneumonia, chronic hepatic disease, and ulcer disease) within the first year after schizophrenia diagnosis. The IRRs of most physical illnesses declined over 3 years, except for that of cerebrovascular disease, which significantly increased (IRR > 3.0) over the 3 years after schizophrenia diagnosis. Cerebrovascular disease had a significant incidence risk (IRR > 3) persistently across the 3 years. Various comorbid physical illnesses can occur in the early stages of schizophrenia. Clinicians should consider these vulnerabilities to physical illnesses during the evaluation of patients with newly diagnosed schizophrenia by attempting to prevent, screen for, and manage them. [ABSTRACT FROM AUTHOR]

Objectives: Patients with bipolar disorder are at high risk of cardiovascular diseases. Among cardiovascular diseases, coronary heart disease and stroke are the leading causes of premature death and both share the pathogenesis of arterial atherosclerosis. Increased carotid intima-media thickness is sensitive for detecting early atherosclerosis and a practical index for predicting cardiovascular diseases. However, few studies investigated carotid intima-media thickness in adults with bipolar disorder. We attempted to determine the factors associated with carotid intima-media thickness in adults with bipolar disorder. Methods: The euthymic out-patients with bipolar I disorder aged over 20 years were recruited to measure the carotid intima-media thickness value through B-mode carotid ultrasound. Those with any psychiatric disorder, acute or life-threatening medical condition were excluded. All clinical information was obtained by reviewing medical records and directly interviewing patients with reliable others. Results: Of the 106 participants with a mean age of 44.5 years, 40.6% (N = 43) had concurrent cardiovascular/endocrine/metabolic diseases. A multivariate regression indicated that higher assumed daily lithium dosage was significantly associated with a decreased carotid intima-media thickness in the whole sample. In the young subgroup (⩽45 years old, N = 63), higher current daily lithium dosage and lower body mass index were associated with lower carotid intima-media thickness. In those without concurrent cardiovascular/endocrine/metabolic diseases, higher ratio of first-generation antipsychotics exposure in relation to illness chronicity was associated with higher carotid intima-media thickness, after controlling for body mass index or age. Conclusion: Lithium treatment may be associated with less progression in carotid intima-media thickness and the reduced risk for atherosclerosis in adults with bipolar disorder, including those with high cardiovascular disease risk. In addition to age and body mass index, antipsychotics may increase carotid intima-media thickness even in the low cardiovascular disease-risk patients. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a debilitating mental illness that causes significant disability. However, the lack of evidence for functional decline yields difficulty in distinguishing patients with schizophrenia from healthy adults. Since patients with schizophrenia demonstrate severe facial emotion recognition deficit (FERD), FERD measurement appears to be a promising solution for the aforementioned challenge.We aimed to develop a FERD-based screening tool to differentiates patients with schizophrenia from healthy adults.Methods: Patients' responses were extracted from a previous study. The most discriminative index was determined by comparing the area under the receiver operating characteristic curve (AUC) of patients' FER scores in 7 domains individually and collectively. The best cut-off score was selected only for the most discriminative index to provide both high sensitivity and specificity (≥ 0.90).Results: The "number of domains failed" showed the highest discriminative value (AUC = 0.92). Since high sensitivity and specificity could not be achieved simultaneously, two sub-optimal cut-off scores were recommended for prospective users. For users prioritizing sensitivity, the "≥ 2 domains failed" index yields high sensitivity (0.96) with modest specificity (0.66). For users targeting specificity, the "≥ 4 domains failed" indexachieves high specificity (0.92) with acceptable sensitivity (0.72).Limitations: Convenience sampling with mild clinical severity and younger healthy adults (< 20 years old) may limit the generalizability.Conclusion: The FERD screener seems to be a discriminative tool with changeable cut-off scores achieving high sensitivity or specificity. Therefore, it may be useful in detecting patients and ruling out adults erroneously suspected of having schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Difficulties in prognostication are common deterrents to palliative care among dementia patients. This study aimed to evaluate the effectiveness of palliative care in reducing the extent of utilization of medical services and the potential risk factors of mortality among dementia patients receiving palliative care. Methods: We surveyed dementia patients involved in a palliative care program at a long-term care facility in Taipei, Taiwan. We enrolled 57 patients with advanced dementia (clinical dementia rating ≥ 5 or functional assessment staging test stage 7b). We then compared the extent of their utilization of medical services before and after the provision of palliative care. Based on multivariable logistic regression, we identified potential risk factors before and after the provision of palliative care associated with 6-month mortality. Results: The utilization of medical services was significantly lower among dementia patients after the provision of palliative care than before, including visits to medical departments (p < 0.001), medications prescribed (p < 0.001), frequency of hospitalization (p < 0.001), and visits to the emergency room (p < 0.001). Moreover, patients dying within 6 months after the palliative care program had a slightly but not significantly higher number of admissions before receiving hospice care (p = 0.058) on univariate analysis. However, no significant differences were observed in multivariate analysis. Conclusions: The provision of palliative care to dementia patients reduces the extent of utilization of medical services. However, further studies with larger patient cohorts are required to stratify the potential risk factors of mortality in this patient group. [ABSTRACT FROM AUTHOR]

Methamphetamine is a prevalent recreational drug among men who have sex with men (MSM) living with HIV and could cause the cognitive impairment and memory loss. However, studies on the association between methamphetamine use and adherence to antiretroviral treatment (ART) are limited and had inconsistent findings. This study aimed to determine the impact of methamphetamine use on adherence to ART among MSM living with HIV. From December 2018 to October 2019, MSM living with HIV were recruited (N = 351) and non-adherence to ART was defined as a Medication Adherence Report Scale score of <23. Overall, 16.0% of the participants reported methamphetamine use in the prior three months and 13.4% of the participants had non-adherence to ART. The proportion of non-adherence to ART among HIV-positive MSM were 28.6% and 10.5% with and without methamphetamine use, respectively. After controlling for demographics, illicit drug use, and co-morbidities, methamphetamine use during the prior three months was associated with a higher risk of non-adherence to ART (adjusted odds ratio = 3.08; 95% confidence intervals: 1.24–7.69). Compared with HIV-positive MSM with non-adherence to ART, HIV-positive MSM with good adherence to ART had a higher CD4 counts and were more likely to achieve an undetectable viral load. Since poor adherence to ART is associated with an increased HIV viral load and the risk of HIV transmission to others, our study suggests that it is imperative to screen HIV-positive patients for methamphetamine use and to provide effective therapy to reduce methamphetamine use and the associated non-adherence to ART. [ABSTRACT FROM AUTHOR]

Background: Few studies have analyzed healthcare utilization before suicide among individuals with attention-deficit/hyperactivity disorder (ADHD). This study examined the pattern of healthcare utilization and comorbidities shortly before death among patients with ADHD who died by suicide and compared these data with those of living controls. This study used Taiwan's National Health Insurance Research Database to identify patients with ADHD (N = 379,440) between January 1, 2001, and December 31, 2016. Subsequently, the researchers identified 159 suicide decedents by linking each patient with the National Mortality Database. By conducting a nested case–control study with risk-set sampling from the ADHD cohort, the researchers selected 20 age- and sex-matched controls (n = 3180) for each patient who died by suicide (cases). The researchers then applied conditional logistic regression to investigate differences in healthcare utilization as well as psychiatric and physical comorbidities between case patients and controls. Case patients had higher healthcare utilization within 3 months before suicide, particularly in the psychiatry, emergency, internal medicine, neurosurgery, and plastic surgery departments. These patients also had higher risks of psychiatric comorbidities, including schizophrenia, bipolar disorder, depressive disorder, and sleep disorder, as well as physical comorbidities such as hypertension and other forms of heart disease. Among patients with ADHD, suicide decedents had increased healthcare utilization and higher risks of specific psychiatric and physical comorbidities than living controls. Thus, for suicide prevention among individuals with ADHD, suicide risk must be detected early and comorbidities should be adequately managed. [ABSTRACT FROM AUTHOR]

Objectives: Studies on cancer incidence and mortality in patients with schizophrenia have reported inconsistent findings. In this study, we simultaneously investigated cancer incidence and mortality in patients with schizophrenia and evaluated the cancer mortality‐to‐incidence ratio (MIR), which is rare in the literature. Methods: From the Taiwan National Health Insurance Database, we collected the data of 107,489 patients who received a diagnosis of schizophrenia between 2000 and 2019. Data regarding cancer incidence and mortality were obtained from the Taiwan Cancer Registry and National Mortality Database, respectively. In total, 3881 incident cancer cases and 2288 cancer mortality cases were identified. Standardized incidence ratios (SIRs), mortality rate ratios (MRRs), and MIRs were compared between patients with schizophrenia and the general population. Results: The overall rate of cancer incidence was slightly lower (SIR: 0.95; 95% confidence interval [CI]: 0.92–0.98; p < 0.001) and that of cancer mortality was higher (MRR: 1.29; 95% CI: 1.23–1.3; p < 0.001) in patients with schizophrenia than in the general population. The MIR for overall cancer was significantly higher in the patients with schizophrenia. The relative MIR (MIR of patients with schizophrenia divided by that of the general population) was 1.36 (95% CI: 1.30–1.42). Conclusion: The MIR was significantly higher in the patients with schizophrenia than in the general population, indicating the possible presence of healthcare disparities. Additional studies are required to investigate the potential association between the significantly higher MIR in patients with schizophrenia and healthcare disparities. [ABSTRACT FROM AUTHOR]

Highlights • We found non-traditional CVD risk factors for early circulatory mortality in patients with schizophrenia. • Longer duration of antipsychotic treatment was associated with a lower circulatory mortality risk. • Higher leukocyte counts at acute hospitalization were associated with a higher circulatory mortality risk. • Our findings suggest systemic inflammation and inadequate treatment might be related to early circulatory mortality. Abstract Patients with schizophrenia have higher mortality and shortened life expectancy than the general population, and cardiovascular disease (CVD) accounts for up to 50% cases of early mortality in schizophrenia. We determined risk factors, particularly pathophysiological changes, for early circulatory mortality in schizophrenia. In this multi-institutional, nested, case–control study, we enrolled consecutive inpatients with schizophrenia admitted to three psychiatric hospitals in the northern Taiwan. Seventy-nine patients who died of CVD before 65 years of age were identified as cases through record linkage, and 158 controls were randomly selected in a 2:1 ratio through risk-set density sampling, after matching for age (±2 years), sex, and index admission (±3 years). Data were obtained through medical record reviews. At the time of death, the mean age of the patients was 47.5 years (standard deviation = 10.3). Conditional logistic regression revealed that the duration of antipsychotic treatment was significantly associated with a lower risk of early circulatory mortality, and leukocyte counts at index hospitalization were significantly associated with a higher risk. Systemic inflammation may be a risk factor for early circulatory mortality in schizophrenia, but antipsychotic treatment, in particular typical antipsychotic treatment, could be a protective factor. [ABSTRACT FROM AUTHOR]

Objectives: Although alcohol dependence is highly prevalent in patients with bipolar disorder, the causal relationship is not yet well-established. This study estimated the incidence of alcohol dependence in a nationwide bipolar disorder cohort and examined risk factors for alcohol dependence. Methods: Patients aged 15–65 years with consistent bipolar disorder who had their first psychiatric admission between 1999 and 2012 (n = 21,791) were enrolled from the National Health Insurance Research Database in Taiwan. We calculated the adjusted incidence rate ratio of alcohol dependence in the bipolar cohort relative to the general population after stratification by age and sex. In the nested case–control study, we included patients with incident alcohol dependence as cases and four age- and sex-matched controls for each case to analyze health care utilization, comorbidities and concomitant medications between them. Results: We identified 1261 patients with bipolar disorder with incident alcohol dependence. Relative to the general population, the adjusted incidence rate ratio of alcohol dependence was 9.20 in the bipolar cohort. All adjusted incidence rate ratios were high across all age subgroups. Cases had higher psychiatric and nonpsychiatric health care utilization than did controls. Multivariate analysis revealed that cases tended to have cardiovascular disease, diabetes mellitus, chronic hepatic disease, pneumonia and delirium before alcohol dependence diagnosis. Cases had higher psychiatric comorbidities, namely drug-induced mental disorders, anxiety disorder, personality disorder, adjustment disorder and sleep disorder. Conclusion: The bipolar cohort had a higher incidence of alcohol dependence. We identified specific groups with a high risk of alcohol dependence. Additional strategies for early detection, treatment and intervention for alcohol dependence should be developed. [ABSTRACT FROM AUTHOR]

Background: This study examined the pattern of medical utilization and the distribution of comorbidities shortly before death among adolescents who died from suicide and compared these data with those of living controls. Methods: From Taiwan's National Health Insurance Research Database, this study identified adolescents aged 10–19 years who died from suicide (n = 935) between 1 January 2000, and 31 December 2016, by linking each patient with the national mortality database. The researchers conducted a nested case–control study through risk set sampling, and for each case, 20 age- and sex-matched controls (n = 18 700) were selected from the general population. The researchers applied conditional logistic regression to investigate differences in medical utilization and physical and psychiatric comorbidities between cases and controls. Results: Cases had a higher proportion of contact with the psychiatric department but a similar proportion of contact with any non-psychiatric medical department within 1 year before suicide compared with controls. There were 18.6% of adolescent suicide victims who only had contacted with a psychiatric department 3 months before suicide. Moreover, cases had a higher proportion of contact with non-psychiatric services within 3 months before suicide, particularly with emergency, surgery, and internal medicine departments. Cases had higher risks of several psychiatric disorders and physical illnesses, including heart diseases, pneumonia, and ulcer disease, than did controls. Conclusions: The findings of increased medical utilization and higher risks of physical and psychiatric comorbidities in adolescent suicide victims are crucial for developing specific interventions to prevent suicide in this population. [ABSTRACT FROM AUTHOR]

Aim: The change in psychiatric diagnoses in clinical practice is not an unusual phenomenon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders is a major clinical issue because of the differences in treatment regimens and long‐term prognoses. In this study, we used a nationwide population‐based sample to compare the diagnostic consistency and interchange rate between schizophrenic disorders and bipolar disorders. Methods: In total, 25 711 and 11 261 patients newly diagnosed as having schizophrenic disorder and bipolar disorder, respectively, were retrospectively enrolled from the Psychiatric Inpatient Medical Claims database between 2001 and 2005. We followed these two cohorts for 7 years to determine whether their diagnoses were consistent throughout subsequent hospitalizations. The interchange between the two diagnoses was analyzed. Results: In the schizophrenic disorder cohort, the overall diagnostic consistency rate was 87.3% and the rate of change to bipolar disorder was 3.0% during the 7‐year follow‐up. Additional analyses of subtypes revealed that the change rate from schizoaffective disorder to bipolar disorder was 12.0%. In the bipolar disorder cohort, the overall diagnostic consistency rate was 71.9% and the rate of change to schizophrenic disorder was 8.3%. Conclusion: Changes in the diagnosis of a major psychosis are not uncommon. The interchange between the diagnoses of schizophrenic disorders and bipolar disorders might be attributed to the evolution of clinical symptoms and the observation of preserved social functions that contradict the original diagnosis. While making a psychotic diagnosis, clinicians should be aware of the possibility of the change in diagnosis in the future. [ABSTRACT FROM AUTHOR]

Background: Evidence on sex-specific incidence and comorbidity risk factors of suicide among patients with bipolar disorder is scarce. This study investigated the sex-specific risk profiles for suicide among the bipolar disorder population in terms of incidence, healthcare utilization and comorbidity. Methods: Using data from the Taiwan National Health Insurance Research Database between 1 January 2000 and 31 December 2016, this nationwide cohort study included patients with bipolar disorder (N = 46 490) and individuals representative of the general population (N = 185 960) matched by age and sex at a 1:4 ratio. Mortality rate ratios (MRRs) of suicide were calculated between suicide rates of bipolar disorder cohort and general population. In addition, a nested case–control study (1428 cases died by suicide and 5710 living controls) was conducted in the bipolar disorder cohort to examine the sex-specific risk of healthcare utilization and comorbidities. Results: Suicide risk was considerably higher in the cohort (MRR = 21.9) than in the general population, especially among women (MRR = 35.6). Sex-stratified analyses revealed distinct healthcare utilization patterns and physical comorbidity risk profiles between the sexes. Although female patients who died by suicide had higher risks of nonhypertensive cardiovascular disease, pneumonia, chronic kidney disease, peptic ulcer, irritable bowel syndrome, and sepsis compared to their living counterparts, male patients who died by suicide had higher risks of chronic kidney disease and sepsis compared to the living controls. Conclusions: Patients with bipolar disorder who died by suicide had sex-specific risk profiles in incidence and physical comorbidities. Identifying these modifiable risk factors may guide interventions for suicide risk reduction. [ABSTRACT FROM AUTHOR]

Objectives: People with bipolar disorder have an elevated risk of mortality. This study evaluated associations between the use of mood stabilizers and the risks of all‐cause mortality, suicide, and natural mortality in a national cohort of people with bipolar disorder. Methods: In this nationwide cohort study, we used data from January 1, 2000, to December 31, 2016, collected from Taiwan's National Health Insurance Research Database and included 25,787 patients with bipolar disorder. Of these patients, 4000 died during the study period (including 760 and 2947 from suicide and natural causes, respectively). Each standardized mortality ratio (SMR) was calculated as the ratio of observed mortality in the bipolar cohort to the number of expected deaths in the general population. Multivariable Cox proportional hazards regression with a time‐dependent model was performed to estimate the hazard ratio (HR) of each mood stabilizer with each mortality outcome. Results: The SMRs of all‐cause mortality, suicide, and natural mortality in the bipolar disorder cohort were 5.26, 26.02, and 4.68, respectively. The use of mood stabilizers was significantly associated with decreased risks of all‐cause mortality (adjusted HR [aHR] = 0.58, p< 0.001), suicide (aHR = 0.60, p < 0.001), and natural mortality (aHR = 0.55, p < 0.001) within a 5‐year follow‐up period after index admission. Among the individual mood stabilizers, lithium was associated with the lowest risks of all‐cause mortality (aHR = 0.38, p < 0.001), suicide (aHR = 0.39, p < 0.001), and natural mortality (aHR = 0.37, p < 0.001). Conclusion: In addition to having protective effects against suicide and all‐cause mortality, mood stabilizers also exert a substantial protective effect against natural mortality, with lithium associated with the lowest risk of mortality. [ABSTRACT FROM AUTHOR]

Introduction Patients with schizophrenia before reaching geriatric age are at high risk of circulatory mortality. However, investigations are lacking on the characteristics of physiological measurement among these at-risk patients. Methods In this study, we followed acutely inpatients with schizophrenia disorder for cause of death through record linkage to the Death Certification System in Taiwan. Cases of patients who died because of circulatory morbidity ( ICD-9 401-443) before turning 65 years old were used. Each schizophrenia case was then matched with two mentally healthy controls for the age and sex, and date of laboratory examination. Clinical data of all subjects were obtained by reviewing medical records. Results Totally, 81 patients with schizophrenia who died from circulatory diseases at mean ages of 48.0 ± 10.7 years were investigated. The mean age at the final acute psychiatric hospitalization was 43.0 ± 10.9 years. Multivariate analysis showed that elevated fasting serum glucose levels (95% confidence interval [ CI] for odds ratio ( OR) = 1.00-1.03), blood leukocyte counts (95% CI for odds ratio ( OR) = 1.07-1.55), and heart rates on electrocardiogram (95% CI for OR = 1.04-1.10) in the final psychiatric hospitalization collectively provided the predictive validity for premature circulatory death. Conclusion Systemic inflammatory activation and autonomic nervous system dysfunction along with dysregulation of glucose metabolism rather than lipids could be the physiological characteristics of schizophrenia patients at risk of premature circulatory mortality. [ABSTRACT FROM AUTHOR]

Background and aims: Alcohol‐related mental health burden and suicidality impose heavy burdens on global public health. This study measured the sex‐specific incidence and risk profiles of suicide mortality in individuals with alcohol dependence in a non‐western context. Design: In this prospective cohort study, individuals with alcohol dependence who were enrollees in Taiwan's National Health Insurance Research database were followed‐up over an almost 15‐year period. Their data were linked to the national mortality registration database. Setting: Taiwan. Participants: In total, 278 345 patients with alcohol dependence were enrolled and followed‐up from 1 January 2001 to 31 December 2016. Measurements We calculated the incidence and standardized mortality ratio (SMR) of suicide in the cohort and stratified the suicide methods by sex. Sex‐specific risk profiles (based on demographic characteristics and physical and psychiatric comorbidities) were generated through Cox proportional hazards regression. Findings The suicide rates of men and women were 173.5 and 158.9 per 100 000 person‐years, respectively (P = 0.097). The SMR of suicide mortality was more than two times higher in women than in men (6.6 versus 15.0). Women and men adopted different suicide methods. A multivariable Cox proportional hazards regression with a time‐varying model revealed that depressive disorder was a common risk factor for suicide in both men and women [adjusted hazard ratio (aHR) = 3.03, 95% confidence interval (CI) = 2.77‐3.31 versus aHR = 5.46, 95% CI = 4.65‐6.40]. For men, receiving a diagnosis of alcohol dependence between the ages of 25 and 44 years, being unemployed and having schizophrenia, drug‐induced mental disorder or sleep disorder were risk factors for suicide. Conclusion: In Taiwan, the incidence of suicide in patients with alcohol dependence is substantially higher than that of the general population. The standardized mortality ratio of suicide in women with alcohol dependence is more than twice that of men with alcohol dependence. [ABSTRACT FROM AUTHOR]

Objective: Medical comorbidities are prevalent in patients with bipolar disorder. Evaluating longitudinal trends of the incidence of medical illnesses enables implementation of early prevention strategies to reduce the high mortality rate in this at-risk population. However, the incidence risks of medical illnesses in the early stages of bipolar disorder remain unclear. This study investigated the incidence and 5-year trend of medical illnesses following bipolar disorder diagnosis. Methods: We identified 11,884 patients aged 13–40 years who were newly diagnosed as having bipolar disorder during 1996–2012 and 47,536 age- and sex-matched controls (1:4 ratio) who represented the general population from Taiwan's National Health Insurance Research Database. We estimated the prevalence and incidence of individual medical illnesses yearly across the first 5 years after the index date. The adjusted incidence rate ratio was calculated to compare the occurrence of specific medical illnesses each year between the bipolar disorder group and control group using the Poisson regression model. Results: Apart from the prevalence, the adjusted incidence rate ratios of most medical illnesses were >1.00 across the first 5-year period after bipolar disorder diagnosis. Cerebrovascular diseases, ischaemic heart disease, congestive heart failure, other forms of heart disease, renal disease and human immunodeficiency virus infection exhibited the highest adjusted incidence rate ratios during the first year. Except for that of renal disease, the 5-year trends of the adjusted incidence rate ratios decreased for cerebrovascular diseases, cardiovascular diseases (e.g. ischaemic heart disease, other forms of heart disease, and vein and lymphatic disease), gastrointestinal diseases (e.g. chronic hepatic disease and ulcer disease) and communicable diseases (e.g. human immunodeficiency virus infection, upper respiratory tract infection and pneumonia). Conclusion: Incidence risks of medical illnesses are increased in the first year after bipolar disorder diagnosis. Clinicians must carefully evaluate medical illnesses during this period because the mortality rates from medical illnesses are particularly high in people with bipolar disorder. [ABSTRACT FROM AUTHOR]

A performance-based measure for assessing executive functions (EF) is useful to understand patients’ real life performance of EF. This study aimed to develop a performance-based measure of executive functions (PEF) based on the Lezak model and to examine psychometric properties (i.e., unidimensionality and reliability) of the PEF using Rasch analysis in patients with schizophrenia. We developed the PEF in three phases: (1) designing the preliminary version of PEF; (2) consultation with experts, cognitive interviews with patients, and pilot tests on patients to revise the preliminary PEF; (3) establishment of the final version of the PEF and examination of unidimensionality and Rasch reliability. Two hundred patients were assessed using the revised PEF. After deleting items which did not satisfy the Rasch model’s expectations, the final version of the PEF contained 1 practice item and 13 test items for assessing the four domains of EF (i.e., volition, planning, purposive action, and effective performance). For unidimensional and multidimensional Rasch analyses, the 4 domains showed good reliability (i.e., 0.77–0.85 and 0.87–0.90, respectively). Our results showed that the PEF had satisfactory unidimensionality and Rasch reliability. Therefore, clinicians and researchers could use the PEF to assess the four domains of EF in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Sepsis constitutes a condition that involves life-threatening organ dysfunction induced by severe infection. This nested case–control study investigated risk factors for severe sepsis and whether antipsychotic use is associated with severe sepsis risk in patients with schizophrenia, a topic that has not been comprehensively explored in previous studies.We selected 39,432 patients with schizophrenia aged between 15 and 65 years from Taiwan’s Psychiatric Inpatient Medical Claims database for the period 2000–2012. The case group comprised patients with severe sepsis after their first psychiatric admission (n = 1382). The case and control groups were randomly matched (1:4) by age, sex and first psychiatric admission (year) and finally comprised 1382 and 5528 individuals, respectively. We employed multivariable conditional logistic regression to identify (1) risk factors (physical illnesses and nonpsychiatric medications) and (2) antipsychotic–severe sepsis associations.Higher numbers of psychiatric admissions and physical illnesses such as delirium, cerebrovascular disease and cancer were significantly associated with a higher risk of severe sepsis. Furthermore, severe sepsis was associated with the use of antithrombotic agents, systemic corticosteroids and agents targeting the renin–angiotensin system. Clozapine (adjusted risk ratio = 1.65) and quetiapine (adjusted risk ratio = 1.59) use were associated with an increased risk of severe sepsis. The use of more than one antipsychotic drug could further increase this risk.Several physical illnesses and nonpsychiatric medications increase the risk of severe sepsis in patients with schizophrenia. Specifically, clozapine or quetiapine use significantly increased the risk of severe sepsis in these patients. [ABSTRACT FROM AUTHOR]

Panic disorder (PD) is associated with high psychiatric and physical comorbidity, but the cause of mortality has not been well studied. This study investigated mortality rates and causes of death in an Asian cohort with PD. We enrolled a nationwide retrospective cohort of 298,466 persons diagnosed with PD from January 1, 2001, to December 31, 2016. Each cohort member was matched with a comparison one randomly selected from the general population with the same sex, age at entry, and birth year. The data of both the PD cohort and the comparison group were linked with the national mortality database to obtain each individual's mortality status. We used mortality rate ratios (MRRs) to compare mortality risks between the patients with PD and the general population. Stratified analysis of mortality risks was performed based on sex and psychiatric comorbidities. PD was associated with a slightly increased mortality risk (MRR, 1.14 [99% CI, 1.11–1.17]). The risk of unnatural death (MRR, 2.83 [99% CI, 2.59–3.10]) was significantly higher among the individuals with PD than among the general population, whereas the risk of overall natural death across all categories was not (MRR, 1.01 [99% CI, 0.98–1.04]). The mortality risk was the highest for suicide (MRR, 4.94 [99% CI, 4.32–5.72]) and was higher in women (MRR, 6.37 [99% CI, 5.25–7.96]) than in men (MRR, 3.77 [99% CI, 3.14–4.64]). Comorbid substance use disorders increased the risk of mortality from natural (MRR, 3.23 [99% CI, 2.59–4.14]) and unnatural (MRR, 9.45 [99% CI, 6.29–17.85]) causes. PD was associated with increased all-cause mortality, especially suicide. Substance use further increased mortality risk in persons with PD. Targeted treatment for substance use and suicide prevention are essential among persons with PD. [ABSTRACT FROM AUTHOR]

Affective switch is an important clinical issue when treating bipolar disorder. Though commonly seen in clinical practice, the benefits of prescribing antidepressants for bipolar depression are still controversial. To date, there have been few genetic studies and no genome-wide association study (GWAS), focusing on manic switch following bipolar depression. This study aims to investigate the effects of individual genomics and antidepressant medication on the risk of manic switch in bipolar I disorder (BPI). A total of 1004 patients with BPI who had at least one depressive episode with complete data on antidepressant treatment and outcome were included. Clinical assessment of mania and depression was performed by trained psychiatric nurses and psychiatrists using the Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), and the diagnosis of BPI was made according to DSM-IV criteria. Manic switch was defined as a manic episode occurring within eight weeks of remission from an acute depressive episode. The age at first depressive episode of the study patients was 30.7 years (SD 12.5) and 56% of all patients were female. GWAS was carried out in a discovery group of 746 patients, followed by replication in an independent group of 255 patients. The top SNP rs10262219 on chromosome 7 showed the strongest allelic association with manic switch (p = 2.21 × 10−7) in GWAS, which was however not significantly replicated. Antidepressant treatment significantly (odds ratio 1.7; 95% CI 1.3–2.2; p < 0.001) increased the risk of manic switch. In logistic regression analysis, the CC genotype of rs10262219 (odds ratio 3.0; 95% CI 1.7–5.2) and antidepressant treatment (odds ratio 2.3; 95% CI 1.4–3.7) significantly increased the risk of manic switch with a joint effect (odds ratio 5.9; 95% CI 3.7–9.4). In conclusion, antidepressant medication and rs10262219 variants jointly increased the risk of manic switch after bipolar depression. [ABSTRACT FROM AUTHOR]

Background: Evidence of patterns of medical utilization and distribution of comorbidities among individuals using methamphetamine remains limited Objective: This study aims to investigate changes in medical utilization and comorbidities before and after a diagnosis of methamphetamine use disorder. Methods: A total of 3321 cases (79% were male) of methamphetamine use disorder between January 1, 1996, and December 31, 2012, were identified from Psychiatric Inpatient Medical Claims database in Taiwan. Information was collected on demographics, diagnoses, and medical utilizations. The date of newly diagnosed with methamphetamine use disorder was defined as the baseline. Mirror-image study design was used to compare changes in medical utilization and comorbidities between the pre-baseline period (within 1 year before diagnosis) and the post-baseline period (within 1 year after diagnosis). Conditional logistic regression was used to estimate changes in medical utilization and comorbidities. Results: Most cases (77%) were first identified in a psychiatric department. There is a significant increase (P <.001) in psychiatric admission (odds ratio[OR] = 2.19), psychiatric emergency visits (OR = 1.31), and psychiatric outpatient visits (OR = 1.15) after diagnosis. Multivariable analysis revealed significantly increased risks (P <.001) of non-methamphetamine drug induced mental disorders (adjusted OR[aOR] = 29.47), schizophrenia (aOR = 2.62), bipolar disorder (aOR = 2.14), organic mental disorder (aOR = 1.82), and upper respiratory tract infection (aOR = 2.03) after diagnosis. Conclusions: We found significant increases of medical utilization and psychiatric comorbidities after diagnosed with methamphetamine use disorder. These findings may reflect the problem of delayed diagnosis and treatment. Enhancement of early identification of methamphetamine use disorder in general practice is required for early intervention and decreased subsequent morbidities. [ABSTRACT FROM AUTHOR]

• An error-based detectability index was proposed for unbiased error patterns. • Four error patterns were found in patients with schizophrenia. • Corresponding interventions may be provided based on the four error patterns. • The newly proposed detectability may be an indicator of treatment outcome. • Cross-validations are warranted for the suitability as an outcome measurement. Error patterns of facial emotion recognition (FER) indicate how individuals misinterpret others' facial expressions, which helps clinicians to manage related deficits. However, previous investigations are limited and may have been biased due to methodological issues (e.g., no consideration of response bias). This study aimed to propose a detectability index (d') for adjusting response bias and examine the error patterns of FER in patients with schizophrenia. Responses to 168 photos showing seven basic emotions, obtained from 351 patients with schizophrenia and 101 healthy adults, were extracted from a previous study. The differences in the d' s between the two groups (Δ d') were calculated to examine the error patterns of FER among the seven emotions. The findings were generally overlapped with those identified by the traditional confusion matrix. Four error patterns were found. First, the patients were insensitive to some negative emotions (i.e., sadness [ Δ d' = 0.83] and fear [ Δ d' = 0.72]). Second, they misrecognized happy faces as showing negative emotions (e.g., disgust [ Δ d' = 0.43] and sadness [ Δ d' = 0.37]). Third, they misinterpreted surprised faces as all the other emotions (Δ d' = 0.41–0.87), except neutral. Fourth, they confused some negative emotions (e.g., misrecognizing fear as anger [ Δ d' = 0.87]). Our findings suggest that patients with schizophrenia show four error patterns of FER compared to healthy adults. Accordingly, interventions could be selected to improve their sensitivity to faces with negative emotions, differentiation of faces among positive and negative emotions, understanding of surprised faces, and discrimination of faces with negative emotions. [ABSTRACT FROM AUTHOR]

Error patterns of facial emotion recognition (FER) indicate how individuals misinterpret others' facial expressions, which helps clinicians to manage related deficits. However, previous investigations are limited and may have been biased due to methodological issues (e.g., no consideration of response bias). This study aimed to propose a detectability index (d') for adjusting response bias and examine the error patterns of FER in patients with schizophrenia. Responses to 168 photos showing seven basic emotions, obtained from 351 patients with schizophrenia and 101 healthy adults, were extracted from a previous study. The differences in the d's between the two groups (Δd') were calculated to examine the error patterns of FER among the seven emotions. The findings were generally overlapped with those identified by the traditional confusion matrix. Four error patterns were found. First, the patients were insensitive to some negative emotions (i.e., sadness [Δd' = 0.83] and fear [Δd' = 0.72]). Second, they misrecognized happy faces as showing negative emotions (e.g., disgust [Δd' = 0.43] and sadness [Δd' = 0.37]). Third, they misinterpreted surprised faces as all the other emotions (Δd' = 0.41-0.87), except neutral. Fourth, they confused some negative emotions (e.g., misrecognizing fear as anger [Δd' = 0.87]). Our findings suggest that patients with schizophrenia show four error patterns of FER compared to healthy adults. Accordingly, interventions could be selected to improve their sensitivity to faces with negative emotions, differentiation of faces among positive and negative emotions, understanding of surprised faces, and discrimination of faces with negative emotions. [ABSTRACT FROM AUTHOR]

Background and aims: Although methamphetamine use is a serious public health problem, large‐scale cohort studies assessing methamphetamine‐related mortality are scant. This study investigated all‐cause mortality and suicide methods in people with methamphetamine use disorder. Design A cohort record‐linkage study using data from Taiwan's National Health Research Institute Database (NHIRD) linked to Taiwan's National Death Certification System. Setting: Taiwan. Participants: A total of 23 248 individuals with methamphetamine use disorder between 1 January 2001 and 31 December 2005. Measurements The outcome variables included mortality rates and standardized mortality ratios (SMRs) for all causes of death and for each suicide method. Findings Compared with the general population, the current cohort had an increased all‐cause mortality (SMR = 5.4), with the SMR for unnatural causes (14.8) higher than that for natural causes (7.5). Among all causes of death, suicide had the highest SMR (16.3), followed by neurological diseases (9.7). Among the methods of choice for suicide, drug overdose had the highest SMR (24.9). The incidence of charcoal burning and hanging was significantly higher in men and that of jumping from a high place was significantly higher in women. Conclusion: People in Taiwan with methamphetamine use disorder appear to have a significantly increased all‐cause mortality rate compared with the general population, with suicide having the highest contribution, particularly suicide via drug overdose. The methods of choice for suicide revealed distinct patterns between men and women. [ABSTRACT FROM AUTHOR]

Background Facial emotion recognition deficit (FERD) seems to be an obvious feature of patients with schizophrenia and has great potential for classifying patients and non-patients. The FERD screener was previously developed to classify patients from healthy adults. However, an obvious drawback of this screener is that the recommended cut-off scores could enhance either sensitivity or specificity (about 0.92) only, while the other one is at an only acceptable level (about 0.66). Machine learning (ML) algorithms are famous for their feature extraction and data classification abilities, which are promising for improving the discriminative power of screeners. This study aimed to improve the discriminative power of the FERD screener using an ML algorithm. Methods The data were extracted from a previous study. Artificial neural networks were generated to estimate the probability of being a patient with schizophrenia or a healthy adult based on the examinee's responses on the FERD screener (168 items). The performances of the ML-FERD screener were examined using a stratified five-fold cross-validation method. Results Across the five subsets of data, the ML-FERD screener showed extremely high areas under the receiver operating characteristic curve of 0.97-0.99. With the optimized cut-off scores, the average sensitivity and specificity of the ML-FERD screener were 0.90 (0.85-0.93) and 0.93 (0.86-1.00), respectively. Limitations The characteristics of patients were not representative, and the age was mismatched to control group. Conclusion The ML-FERD screener appears to have a better discriminative power to classify patients with schizophrenia and healthy adults than does the FERD screener. [ABSTRACT FROM AUTHOR]

Purpose: Suicide is a leading cause of death in patients with schizophrenia. This nationwide cohort study investigated the incidence of each suicide method in patients with schizophrenia compared with the general population. Methods: In total, records of 174,039 patients with schizophrenia were obtained from the National Health Insurance Research Database in Taiwan from 2001 to 2016. This schizophrenia cohort was linked with the national mortality database, and 26,926 patients died during this follow-up period. Of the deceased, 3033 had died by suicide. Univariate Cox regression was used to estimate the demographic variables associated with suicide. We estimated the difference in the proportion of each suicide method used in patients with schizophrenia compared with the general population. The incidence and standardized mortality ratio (SMR) of each suicide method were calculated and stratified based on sex. Results: Patients aged 25–34 years exhibited the highest suicide risk. Compared with the general population, patients with schizophrenia were more likely to commit suicide by jumping and drowning and less likely to use charcoal-burning and hanging. Women showed a higher incidence of suicide by drowning and jumping than did men. Comorbidity with substance use disorders (SUDs) was associated with a high suicide SMR (26.9, 95% confidence interval [CI] = 23.4–28.9), particularly for suicide by jumping (61.2, 95% CI = 48.3–76.3). Conclusions: Patients with schizophrenia had higher suicide rates for all methods than did the general population. Suicide method differed based on sex. Patients with SUDs exhibit a high SMR for each suicide method and warrant intensive clinical attention. [ABSTRACT FROM AUTHOR]

Objective: The pathogenesis of sudden cardiac death may differ between younger and older adults in schizophrenia, but evidence remains scant. This study investigated the age effect on the incidence and risk of the physical and psychiatric comorbidity for sudden cardiac death.Methods: Using 2000 to 2016 data from the Taiwan National Health Insurance Research Database and Department of Health Death Certification System, we identified a national cohort of 170,322 patients with schizophrenia, 1,836 of whom had a sudden cardiac death. Standardized mortality ratios (SMRs) were estimated. Hazard ratios and population attributable fractions of distinctive comorbidities for sudden cardiac death were assessed.Results: The SMRs of sudden cardiac death were all >1.00 across each age group for both sexes, with the highest SMR in male patients aged <35 years (30.88, 95% CI: 26.18-36.18). The fractions of sudden cardiac death attributable to hypertension and congestive heart failure noticeably increased with age. By contrast, the fraction attributable to drug-induced mental disorder decreased with age. Additionally, chronic hepatic disease and sleep disorder increased the risk of sudden cardiac death in patients aged <35 years. Dementia and organic mental disorder elevated the risk in patients aged between 35-54 years. Ischemic heart disease raised the risk in patients aged ≥55 years.Conclusions: The risk is increased across the lifespan in schizophrenia, particularly for younger male patients. Furthermore, physical and psychiatric comorbidities have age-dependent risks. The findings suggest that prevention strategies targeted toward sudden cardiac death in patients with schizophrenia must consider the age effect. [ABSTRACT FROM AUTHOR]

Objective: The authors investigated the distributions and trajectories of physical illnesses preceding the diagnosis of bipolar disorder with comparison to schizophrenia and general populations.Methods: Using data from the Taiwan National Health Insurance Research Database entered from 1996 to end of 2012, we identified 13,079 patients newly diagnosed as having bipolar disorder between the age of 13 and 40 years (ie, cases). For each case with bipolar disorder, two age- and sex- and diagnosis year- schizophrenia comparisons (n=26,158)(n=26,158) and four age- and sex-matched comparisons representing the general population (n=52,316)(n=52,316) were randomly selected from the cohort. Multivariate conditional logistic regression analyses were conducted to estimate the risk of physical illness before the diagnosis (index date). Variables exhibiting a powerful association (p<0·001) were retained in the final model.Results: During the year before diagnosis, patients with newly diagnosed bipolar disorder had a higher risk of numerous physical illnesses across the cardiovascular, respiratory, gastrointestinal, endocrine/metabolic, and musculoskeletal/integument systems compared with those with schizophrenia and the general population. Trends in the risk of specific physical illnesses, mainly hypertension, heart disease, asthma, ulcer disease, hyperlipidemia, and connective tissue disease, were increased across the 3-year prodromal phase of bipolar disorder relative to schizophrenia.Conclusions: Intriguingly, physical illnesses before the diagnosis of bipolar disorder are pervasive with higher risk. Moreover, the trajectories of physical illnesses markedly differ from those of schizophrenia before full manifestation. [ABSTRACT FROM AUTHOR]

Home care case management (CM) is the main intervention for patients with severe mental disorders (SMDs) requiring outreach care. This study investigated the long-term mortality outcome and associated risk factors in patients who received home care CM. This nationwide study enrolled patients who received home care CM (n = 10,255) between 1 January 1999 and 31 December 2010. Each patient was followed up from the baseline (when patients underwent home case CM for the first time during the study period) to the censor (i.e. mortality or the end of the study). We calculated the standardized mortality ratio (SMR) and presented by age and diagnosis. Multivariate regression was performed to assess independent risk factors for mortality. Among 10,255 patients who received home care CM, 1409 died during the study period; the overall SMR was 3.13. Specifically, patients with organic mental disorder had the highest SMR (4.98), followed by those with schizophrenia (3.89), major depression (2.98), and bipolar disorder (1.97). In the multivariate analysis, patients with organic mental disorder or dementia had the highest risk, whereas the mortality risk in patients with schizophrenia was comparable to that in patients with bipolar disorder or major depression. Deceased patients had a significantly higher proportion of acute or chronic physical illnesses, including cancer, chronic hepatic disease, pneumonia, diabetes mellitus, cardiovascular disease, and asthma. This study presented the gap of mortality in patients with SMDs receiving home care CM in Taiwan. We highlight the need for effective strategies to improve medical care for this specified population. [ABSTRACT FROM AUTHOR]

Aim: Research regarding the effects of age in patients with schizophrenia taking antipsychotics on the risk of sudden cardiac death is lacking. We determined the effect of patient age on the association between exposure to antipsychotics and the risk of sudden cardiac death in a nationwide schizophrenia cohort. Methods: From the Taiwan National Health Insurance Research Database and Department of Health Death Certification System, data of 1836 patients with schizophrenia who had experienced sudden cardiac death between 2000 and 2016 were included. A case–crossover design by using a 14‐day window was applied, and subgroup analyses were performed by stratifying patients into three age subgroups (<45, 45–65, and >65 years) to assess the effect of age on the risk of sudden cardiac death in patients taking antipsychotics. Results: No association between exposure to antipsychotic agents and sudden cardiac death risk was found in patients aged >65 years who were characterized by a high burden of medical illnesses. However, zotepine significantly increased the risk of sudden cardiac death in patients aged <45 years (adjusted relative risk [RR] = 2.68, P = 0.046). Flupentixol (adjusted RR = 5.30, P = 0.004) and risperidone (adjusted RR = 1.68, P = 0.01) significantly elevated the risk of sudden cardiac death in patients aged 45–65 years. Conclusion: This study suggests that individual antipsychotics pose different risks of sudden cardiac death in patients with schizophrenia across their lifespan. Clinicians should consider patient age when evaluating the risks and benefits of antipsychotic treatment. [ABSTRACT FROM AUTHOR]

Objective: Data on the incidence and risk factors of sudden cardiac death in patients with bipolar disorder are lacking in the literature.Methods: By using data from the Taiwan National Health Insurance Research Database and Department of Health Death Certification System between 2000 and 2016, we conducted a prospective national cohort study to determine the incidence and risk factors of sudden cardiac death in bipolar disorder patients. The study cohort included 46,490 patients with bipolar disorder, 467 of whom experienced sudden cardiac death.Results: Stratified analyses showed that the standardized mortality ratios (SMRs) of sudden cardiac death were all above 1.00 across each age interval, with the highest SMR in patients aged <30 years (31.96, 95% CI: 20.47-47.55). Notably, hypertension raised the risk of sudden cardiac death in both patients aged <50 years (1.85, 95% CI: 1.23-2.79) and aged ≥50 years (1.44, 95% CI: 1.14-1.83). In addition, venous and lymphatic disorders (1.97, 95% CI: 1.23-3.16), and alcohol use-related disorder (2.34, 95% CI: 1.62-3.38) elevated the risk of sudden cardiac death in patients aged <50 years. Congestive heart failure (1.59, 95% CI: 1.13-2.23) and dementia (1.75, 95% CI: 1.30-2.35) increased the risk of sudden cardiac death in patients aged ≥50 years.Conclusions: The risk of sudden cardiac death is remarkably high in bipolar disorder patients across the lifespan. Prevention strategies specific to individuals with bipolar disorder are urgently required. [ABSTRACT FROM AUTHOR]

Aim Research regarding the effect of antipsychotic medications on the risk of upper respiratory infection (URI) progression to pneumonia in patients with schizophrenia is rare. This study investigated the effect of antipsychotic use on the risk of URI progression to pneumonia in patients with schizophrenia.Methods: This cohort study used the Taiwan's Nationwide Psychiatric Inpatient Medical Claims Database. From January 1, 1996 to December 31, 2012, 22,771 patients with schizophrenia were diagnosed as having the first URI episode after their first psychiatric admission and 135 of them developed pneumonia within 30 days. The duration and dosage of antipsychotics were assessed before and after URI. Cox regression with time-dependent model was used to assess the risk of antipsychotic use on the progression of URI to pneumonia.Results: Among first- and second-generation antipsychotics, clozapine was the only medication associated with an increased risk of developing pneumonia before URI (adjusted hazard ratio [aHR] = 2.05, P = .024). Clozapine was also the only drug significantly associated with an increased risk after URI (aHR = 1.92, P = .027). Regarding medication use after URI, the dosage of clozapine was significantly associated with an increased risk based on Cox regression with a time-dependent model (aHR = 1.95, P = .003).Conclusions: The use of clozapine was associated with URI progression to pneumonia in patients with schizophrenia. The dosage of clozapine used in the post-URI period was also associated with an increased risk. Clinicians should consider lowering clozapine dosage in patients with URI to prevent them developing pneumonia. [ABSTRACT FROM AUTHOR]

Aim: Older community‐dwelling patients with severe mental illness (SMI), particularly those with illness onset at young age, constitute a group of survivors with unique long‐term care needs. Using an Asian sample in Taiwan, we attempted to find out the differences in outcomes related to physical health, cognition, and social functioning between older community‐dwelling adults with bipolar disorder and schizophrenia with early age onset. Methods: Community‐dwelling patients aged >50 years with bipolar I disorder or schizophrenia whose illness developed before the age of 40 years were recruited. Clinical data were obtained by reviewing all available medical records and by interviewing the patients and their reliable family members. Medical morbidities, Mini‐Mental State Examination (MMSE), Cumulative Illness Rating Scale for Geriatrics (CIRS‐G), and Global Assessment of Functioning (GAF) scores were compared between the two groups. Results: In total, 113 bipolar patients and 104 schizophrenic ones (mean ages = 59.8 and 59.2 years, respectively) became the final subjects. The rates of cognitive impairment (MMSE score <24) were comparable in bipolar disorder (26.5%) and schizophrenia (24.0%) and the mean MMSE scores did not significantly differ from each other. The concurrence (54.9%) of cardiovascular disease (CVD) in the bipolar group was also similar to 51.0% in the schizophrenic one. In a multiple logistic regression analysis, the bipolar group exhibited significantly higher CIRS‐G total scores (95% confidence interval (CI) for odds ratio (OR) = 1.01–1.27), body mass index (95% CI for OR = 1.02–1.21), and GAF scores (95% CI for OR = 1.04–1.14). Conclusion: Given better social functioning and the same cognitive function in older community‐dwelling patients with bipolar disorder, they may remain at higher risk for obesity and medical morbidity than schizophrenic patients. Treatments targeting cognitive impairment and CVDs across their life span are both necessary to promote the health of community‐dwellers with SMI. [ABSTRACT FROM AUTHOR]

Aim: This nationwide study investigated the change in medical utilization of psychiatric home care case management (CM).Methods: This nationwide study enrolled patients receiving CM (N = 10,274) from January 1, 1999 to December 31, 2010, from Taiwan's National Health Insurance Research Database. Through a 2-year mirror-image comparison weighted by the contributed person-time for each subject, we evaluated changes in medical utilization. Furthermore, a case-crossover analysis was used to verify the independent effect of CM in changing medical utilization by adjusting the time-variant variables between the pre-2-year (within 2 years before receiving CM) and post-2-year (within years after receiving CM) periods. The same methodology was applied for the subsequent 2-year comparison to assess the maintenance effect.Results: Of the 10,274 patients receiving CM, 69.7% had schizophrenia. The results showed a chronological trend for the intervention of CM. The adjusted mirror-image analysis revealed a significant decrement of psychiatric and involuntary admissions after the intervention, and the utilization shifted toward psychiatric outpatient service. The case-crossover analysis with the adjustment of time-variant covariates confirmed the independent effect of CM on the changes of medical utilization. The comparable effect persisted after the next 2 years of intervention. However, CM showed no impact on lowering the admission rate for comorbid physical illnesses after the intervention.Conclusions: The CM model can effectively reduce psychiatric hospitalization and involuntary admission frequency but has no effect on comorbid physical illnesses. Care models aimed at ameliorating physical problems in such patients are needed. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the relationship between benzodiazepine and risk of developing pneumonia in patients with schizophrenia, whose benzodiazepine dosage and usage frequency was higher than that of the general population.Methods: We conducted a nested case-control study to assess the association between benzodiazepine use and pneumonia among patients with schizophrenia. By using the Taiwan National Health Insurance Research Database, we identified a schizophrenia cohort comprising 34,929 patients during 2000-2010. Within the schizophrenia cohort, 2501 cases of pneumonia and 9961 matched control patients (1:4 ratio) were identified. Benzodiazepine exposure was categorized by drug, treatment duration, and daily dose. Conditional logistic regression models were used to examine the association between benzodiazepine exposure and the risk of pneumonia.Results: The current use (within 30 days) of midazolam led to the highest pneumonia risk (adjusted risk ratio = 6.56, P < 0.001), followed by diazepam (3.43, P < 0.001), lorazepam (2.16, P < 0.001), and triazolam (1.80, P = 0.019). Furthermore, nearly all the benzodiazepines under current use had a dose-dependent effect on pneumonia risk. The risk of pneumonia was correlated with the affinities of γ-aminobutyric acid A α1, α2, and α3 receptors.Conclusions: Benzodiazepines had a dose-dependent relationship with pneumonia in patients with schizophrenia. The differences in risk and mechanism of action of the individual drugs require further investigation. Clinicians should be aware of the early signs of pneumonia in patients with schizophrenia receiving benzodiazepines. [ABSTRACT FROM AUTHOR]

Aim: Patients with schizophrenia have a higher incidence of tuberculosis than do people in the general population. Information is limited regarding the association between antipsychotic agents and the risk of tuberculosis in patients with schizophrenia. This exploratory study assessed the risk of tuberculosis among patients with schizophrenia on antipsychotic therapy. Methods: Among a nationwide schizophrenia cohort derived from the National Health Insurance Research Database in Taiwan (n = 32 399), we identified 284 patients who had developed newly diagnosed tuberculosis after their first psychiatric admission. Ten or fewer matched controls were selected randomly from the cohort for each patient based on risk‐set sampling. We categorized exposure to antipsychotic medications by type and defined daily dose. Using multivariate methods, we explored individual antipsychotic agents for the risk of tuberculosis and employed a propensity‐scoring method in sensitivity analyses to validate any associations. Results: Among the antipsychotic agents studied and after adjustment for covariates, current use of clozapine was the only antipsychotic agent associated with a 63% increased risk of tuberculosis (adjusted risk ratio = 1.63, P = 0.014). In addition, the association did not show a clear dose‐dependent relationship. Clozapine combined with other antipsychotic agents showed a potential synergistic risk for tuberculosis (adjusted risk ratio = 2.30, P = 0.044). Conclusion: This exploratory study suggests the potential risk of clozapine on the risk of tuberculosis, especially for those on clozapine in combination with other antipsychotics. Future studies are needed to verify the association. [ABSTRACT FROM AUTHOR]

Background: Patients with alcohol dependence (AD) often seek help from medical professionals due to alcohol-related diseases, but the overall distribution of medical specialties identifying new AD cases is unclear. We investigated how such cases were identified and how medical resources were utilized before the identification of AD in a nationwide cohort.Methods: We enrolled a population-based cohort (N = 1,000,000) using the National Health Insurance Research Database of Taiwan; 8181 cases with incident AD were retrieved between January 1, 2000, and December 31, 2010. For this nested case-control study, four controls were matched for age and sex with each case based on risk-set sampling. We measured various dimensions of medical utilization before AD was diagnosed, including department visited, physical comorbidity, and medication used. Conditional logistic regression was used for estimating the variables associated with AD.Results: Patients living in less urbanized areas who were unemployed were more likely to develop AD. The highest proportions (34.2%) of AD cases were identified in the internal medicine department, followed by the emergency (22.3%) and psychiatry (18.7%) departments. AD patients had a higher risk of comorbid chronic hepatic disease (adjusted RR = 2.72, p < 0.001) before identification of AD than controls. AD patients also had greater numbers of hospital admissions than controls, including non-psychiatric and psychiatric hospitalizations. Outpatient visit numbers were similar for AD patients and controls.Conclusions: The findings indicate that clinicians providing care in diverse medical settings should be prepared to screen for unhealthy alcohol use and to mitigate its detrimental effects. [ABSTRACT FROM AUTHOR]