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.

Antipsychotic medications and severe sepsis in schizophrenia: A nested case-control study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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.

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.

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.

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.

Incidence of and risk factors for alcohol dependence in bipolar disorder: A population-based cohort and nested case-control study.

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.

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.

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.

Age effect of antipsychotic medications on the risk of sudden cardiac death in patients with schizophrenia: A nationwide case-crossover study.

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.

Mood stabilisers and risk of stroke in bipolar disorder.

BACKGROUND: Research on the risk of stroke following the use of mood stabilisers specific to patients with bipolar disorder is limited.AimsIn this study, we investigated the risk of stroke following the exposure to mood stabilisers in patients with bipolar disorder. METHOD: Data for this nationwide population-based study were derived from the Taiwan National Health Insurance Research Database. Among a retrospective cohort of patients with bipolar disorder (n = 19 433), 609 new-onset cases of stroke were identified from 1999 to 2012. A case-crossover study design utilising 14-day windows was applied to assess the acute exposure effect of individual mood stabilisers on the risk of ischaemic, haemorrhagic and other types of stroke in patients with bipolar disorder. RESULTS: Mood stabilisers as a group were significantly associated with the increased risk of stroke in patients with bipolar disorder (adjusted risk ratio, 1.26; P = 0.041). Among individual mood stabilisers, acute exposure to carbamazepine had the highest risk of stroke (adjusted risk ratio, 1.68; P = 0.018), particularly the ischaemic type (adjusted risk ratio, 1.81; P = 0.037). In addition, acute exposure to valproic acid elevated the risk of haemorrhagic stroke (adjusted risk ratio, 1.76; P = 0.022). In contrast, acute exposure to lithium and lamotrigine did not significantly increase the risk of any type of stroke. CONCLUSIONS: Use of carbamazepine and valproic acid, but not lithium and lamotrigine, is associated with increased risk of stroke in patients with bipolar disorder.Declaration of interestNone.

Estimating the Risk of Pneumonia in Patients With Schizophrenia Newly Receiving Clozapine: A Nationwide Cohort Study.

PURPOSE/BACKGROUND: Patients with schizophrenia are vulnerable to pneumonia. Clozapine is associated with the greatest risk of pneumonia. We investigated the risk factors of pneumonia in patients with schizophrenia who use clozapine. METHODS/PROCEDURES: We used a large cohort of patients with schizophrenia (N = 22,774) who newly use clozapine (baseline). We divided the data set into a training cohort (entry between 1998 and 2008, n = 18,496) and test cohort (entry between 2009 and 2012, n = 4278), where 483 and 168 patients developed pneumonia requiring hospitalization within 1 year after baseline, respectively. For prediction, we developed a static model using Cox proportional hazards regression and a dynamic model using Cox regression with time-dependent modeling. Areas under receiver operating curves (AUCs) for the predictive model were estimated in the training cohort and then in the test cohort for validation. FINDINGS/RESULTS: Based on the baseline characteristics, the static model for predicting pneumonia in 3 periods (90, 180, and 365 days) was unsatisfactory (AUCs, 0.64, 0.64, and 0.65, respectively). The predictors were older age, male sex, history of nonpsychiatric hospitalization, dementia, asthma, and tuberculosis within 1 year before baseline. However, the results were improved (AUCs, 0.83, 0.79, and 0.77, respectively) after control for time-dependent variables, namely, duration of clozapine use and concomitant medications (ie, benzodiazepines, valproic acid, systemic corticosteroids). IMPLICATIONS/CONCLUSIONS: Several risk factors for predicting subsequent pneumonia after initial use of clozapine were explored, including older age, male, history of nonpsychiatric hospitalization, dementia, asthma, tuberculosis, benzodiazepines, valproic acid, systemic corticosteroids, and the use duration of clozapine. Clinical staff can use the risk factors to administer evidence-based treatment.

Excessive mortality and causes of death among patients with personality disorder with comorbid psychiatric disorders.

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.

Antipsychotic drugs and risk of newly diagnosed tuberculosis in schizophrenia.

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.

Excess incidence and risk factors for recurrent pneumonia in bipolar disorder.

AIM: Patients with bipolar disorder (BD) tend to have poorer outcomes after pneumonia and could have a higher risk for recurrence of pneumonia. We aimed to investigate the incidence and risk factors of recurrent pneumonia in patients with BD. METHODS: In a nationwide cohort of BD patients (derived from the National Health Insurance Research Database in Taiwan) who were hospitalized for pneumonia between 1996 and 2012, we identified 188 patients who developed recurrent pneumonia after a baseline pneumonia episode. Applying risk-set sampling at a 1:2 ratio, 353 matched controls were selected from the study cohort. We used multivariate conditional logistic regression analysis to explore the association between recurrent pneumonia and physical illness, concomitant medications, and psychotropic drugs. RESULTS: The findings showed that the incidence of recurrent pneumonia in BD was 6.60 cases per 100 person-years, which was higher than that in the general population. About 10% (9.24%) of cases with recurrent pneumonia died within 30 days of hospitalization. Patients had increased risk of recurrent pneumonia if they had hypertension, diabetes mellitus, cancer, or asthma. Conversely, psychotropic drugs, both first- and second-generation antipsychotics, which are known to increase susceptibility to baseline pneumonia, were not associated with risk of pneumonia recurrence. CONCLUSION: We found an excess incidence of recurring pneumonia in patients with BD, and this risk was associated with pre-existing medical conditions but not psychotropic agents. Physicians should carefully consider the comorbid medical conditions of patients with BD that could lead to recurrent pneumonia.

No association of CYP2E1 genetic polymorphisms with alcohol dependence in Han Taiwanese population.

Cytochrome P450 2E1 (CYP2E1) gene is one of the candidate genes for alcohol dependence (AD). Four single nucleotide polymorphisms (SNPs) of CYP2E1 gene (CYP2E1*1D, *5B, *6 and *1B) have been associated with AD previously in other ethnic populations. To date, only CYP2E1*5B and *6 SNPs have been investigated in relation to AD in our population. The objective of the study was to examine the genetic associations of CYP2E1 covering the four above-noted SNPs conjointly with AD in Han Taiwanese population based on single SNP analysis and haplotype-based approach. We enrolled a total of 340 patients fulfilling DSM-IV-TR diagnostic criteria of AD and 319 healthy controls and genotyped them for the above four SNPs of CYP2E1 gene. By comparing the differences of genotype, allele, and pertinent haplotype frequencies, we did not support a genetic association between CYP2E1 and AD in Han Taiwanese either by single allele tests or haplotype-based analyses.