Lipid-modifying agents and risk of all-cause, natural and suicide mortality in schizophrenia: nationwide cohort study.

BACKGROUND: Individuals with schizophrenia face high mortality risks. The effects of lipid-modifying agents on this risk remain understudied. AIM: This study was conducted to investigate the effects of lipid-modifying agents on mortality risk in people with schizophrenia. METHOD: This nationwide cohort study collected the data of people with schizophrenia from Taiwan's National Health Insurance Research Database for the period between 1 January 2001 and 31 December 2019. Multivariable Cox proportional hazards regression with a time-dependent model was used to estimate the hazard ratio for mortality associated with each lipid-modifying agent. RESULTS: This study included 110 300 people with schizophrenia. Of them, 22 528 died (19 754 from natural causes and 1606 from suicide) during the study period, as confirmed using data from Taiwan's national mortality database. The use of lipid-modifying agents was associated with reduced risks of all-cause (adjusted hazard ratio [aHR]:0.37; P < 0.001) and natural (aHR:0.37; P < 0.001) mortality during a 5-year period. Among the lipid-modifying agents, statins and fibrates were associated with reduced risks of all-cause mortality (aHRs:0.37 and 0.39, respectively; P < 0.001 for both) and natural mortality (aHRs: 0.37 and 0.42, respectively; P < 0.001 for both). Notably, although our univariate analysis indicated an association between the use of lipid-modifying agents and a reduced risk of suicide mortality, the multivariate analysis revealed no significant association. CONCLUSIONS: Lipid-modifying agents, particularly statins and fibrates, reduce the risk of mortality in people with schizophrenia. Appropriate use of lipid-modifying agents may bridge the mortality gap between these individuals and the general population.

Sex-specific risk profiles for suicide mortality in bipolar disorder: incidence, healthcare utilization and comorbidity.

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.

Healthcare utilization, psychiatric disorders, and physical illnesses shortly before suicide mortality in adolescents in Taiwan.

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.

Unfavorable cancer mortality-to-incidence ratios in patients with schizophrenia: A nationwide cohort study in Taiwan, 2000-2019.

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.

Mood stabilizers and risk of all-cause, natural, and suicide mortality in bipolar disorder: A nationwide cohort study.

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.

Healthcare utilization and comorbidity shortly before suicide mortality in patients with attention-deficit/hyperactivity disorder: a nested case-control study.

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.

I-line photolithographic metalenses enabled by distributed optical proximity correction with a deep-learning model.

High pattern fidelity is paramount to the performance of metalenses and metasurfaces, but is difficult to achieve using economic photolithography technologies due to low resolutions and limited process windows of diverse subwavelength structures. These hurdles can be overcome by photomask sizing or reshaping, also known as optical proximity correction (OPC). However, the lithographic simulators critical to model-based OPC require precise calibration and have not yet been specifically developed for metasurface patterning. Here, we demonstrate an accurate lithographic model based on Hopkin's image formulation and fully convolutional networks (FCN) to control the critical dimension (CD) patterning of a near-infrared (NIR) metalens through a distributed OPC flow using i-line photolithography. The lithographic model achieves an average ΔCD/CD = 1.69% due to process variations. The model-based OPC successfully produces the 260 nm CD in a metalens layout, which corresponds to a lithographic constant k1 of 0.46 and is primarily limited by the resolution of the photoresist. Consequently, our fabricated NIR metalens with a diameter of 1.5 mm and numerical aperture (NA) of 0.45 achieves a measured focusing efficiency of 64%, which is close to the calculated value of 69% and among the highest reported values using i-line photolithography.

Prevalence and 5-year trend of incidence for medical illnesses after the diagnosis of bipolar disorder: A nationwide cohort study.

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.

Increased medical utilization and psychiatric comorbidity following a new diagnosis of methamphetamine use disorder.

Background: Evidence of patterns of medical utilization and distribution of comorbidities among individuals using methamphetamine remains limitedObjective: 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.

Age Effect on Incidence, Physical, and Psychiatric Comorbidity for Sudden Cardiac Death in Schizophrenia: Effet de l'âge sur l'incidence, la comorbidité physique et psychiatrique de la mort cardiaque subite dans la schizophrénie.

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.

Incidence and method of suicide mortality in patients with schizophrenia: a Nationwide Cohort Study.

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.

Nationwide Analysis of Changes in Medical Utilization Before and After a New Panic Disorder Diagnosis.

OBJECTIVE: Panic disorder (PD) is associated with somatization and high medical utilization in primary care settings. Treatment of PD could reduce the frequency of panic attacks and visits to emergency departments, but the associated change in medical utilization is unknown. This study investigated the change in medical utilization before and after a PD diagnosis. METHOD: This study identified 8722 patients with PD enrolled in the National Health Insurance Research Database in Taiwan between January 1, 2000, and December 31, 2012. We used a case-crossover study design to compare medical utilizations with a 1-year time window before and after new PD diagnoses, including medical examinations, specialty visits, and medication used. A conditional logistic regression model was used to estimate changes in comorbidity before and after new PD diagnoses. RESULTS: The utilization of examinations-including electrocardiography, radiography, and sonography-decreased within 1 year after PD diagnosis compared with 1 year before PD diagnosis. Outpatient and emergency department visits to nonpsychiatric departments decreased (risk ratio [RR] = 0.989 [95% confidence interval {CI} = 0.985-0.993] and RR = 0.924 [95% CI = 0.894-0.956], respectively), whereas outpatient visits to psychiatric departments increased (RR = 1.193, 95% CI = 1.171-1.215). PD diagnosis is associated with increased use of antidepressants (RR = 12.65) and benzodiazepines (RR = 11.63), an increased ratio of comorbid depressive disorder (RR = 3.06) and bipolar disorder (RR = 1.77), and a decreased ratio of nonpanic anxiety disorder (RR = 0.69). CONCLUSIONS: New PD diagnoses are associated with decreased laboratory examination and nonpsychiatric service utilization, along with increased psychiatric service utilization. We suggest that PD should be detected earlier for mitigating potentially unnecessary use of nonpsychiatric examinations and services.

Healthcare Utilization, Physical and Psychiatric Comorbidities Before Self-Injurious Behavior in Patients with Asthma: A Nested Case-Control Study.

Background: Patients with asthma experience more physical, psychological, and financial burdens; a link between asthma and suicidality has been reported in research. Purpose: This study analyzed the medical utilization and comorbidity before their self-injurious behavior in patients with asthma. Methods: We enrolled 186,862 patients newly diagnosed with asthma between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 500 case subjects had ever conducted self-injurious behaviors during the study period. Based on a nested case-control study, each case was matched with 10 controls derived from the asthma cohort to analyze differences between them and their medical use models. Results: The results indicated that, compared to the control group, the cases presented higher frequencies of outpatient visits and hospitalizations. Regarding comorbidity, the cases had more cardiovascular diseases (adjusted odds ratio [aOR]=1.58; p<0.001), bipolar disorder (aOR=2.97; p<0.001), depression (aOR=4.44; p<0.001), and sleep disorder (aOR=1.83; p<0.001) than the controls. Conclusion: The evidence-based information serves as a reference for medical staff to reduce the occurrence of self-injurious behavior in patients with asthma.

Clozapine and its protective effect on all-cause, natural, and suicide mortality in patients with schizophrenia: A nationwide cohort study in Taiwan.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Sex-specific incidences and risk profiles of suicide mortality in people with alcohol dependence in Taiwan.

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.

Premature death and causes of death among patients with panic disorder and comorbid psychiatric disorders: A nationwide cohort study.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Healthcare utilization and psychiatric and physical comorbidities before suicide mortality in patients with methamphetamine use disorder: A nationwide case-control study.

BACKGROUND: Since the late 1990s, methamphetamine use has become a considerable public health concern. Despite high suicide rates among methamphetamine users, studies exploring medical utilization and psychiatric and physical comorbidities before suicide are scant. We aim to examine the pattern of medical utilization and distribution of comorbidities shortly before suicide in methamphetamine users who died of suicide and compared these data with those of living methamphetamine users. METHODS: From Taiwan's National Health Insurance Research Database, we identified the cohort with methamphetamine use disorder (n = 23,248) between January 1, 2001, and December 31, 2005. We identified 5972 deceased patients (of whom 745 died of suicide) by linking each patient with the national mortality database during the study period. By conducting a nested case-control study with risk-set sampling, from the methamphetamine cohort, we selected four age- and sex-matched controls for each patient who died of suicide (cases). We applied conditional logistic regression to investigate differences in medical utilization and physical and psychiatric comorbidities between cases and controls. RESULTS: Cases had higher medical utilization within 3 months before suicide, particularly in the departments of psychiatry, internal medicine, emergency, and family practice. Cases had higher risks of physical comorbidities, including pneumonia and renal disease, and psychiatric comorbidities, including depressive disorder, sleep disorder, drug-induced mental disorder, schizophrenia, and bipolar disorder. CONCLUSIONS: The findings of increased medical utilization and the higher risks of physical and psychiatric comorbidities in cases are crucial for developing specific interventions to prevent suicide in this patient population.

All-cause and suicide mortality among people with methamphetamine use disorder: a nation-wide cohort study in Taiwan.

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.

High Risk and Trajectories of Physical Illnesses before the Diagnosis of Bipolar Disorder.

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.

Incidence and risk factors of sudden cardiac death in bipolar disorder across the lifespan.

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.