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[This corrects the article DOI: 10.1371/journal.pone.0179424.].

BACKGROUND:The association between antipsychotic use and the risk of stroke in schizophrenic patients is controversial. We sought to study the association in a nationwide cohort with schizophrenia. METHODS:Using a retrospective cohort of patients with schizophrenia (N = 31,976) derived from the Taiwan National Health Insurance Research Database, 802 new-onset cases of stroke were identified within 10 years of follow-up (from 2000 through 2010). We designed a case-crossover study using 14-day windows to explore the risk factors of stroke and the association between antipsychotic drugs and the risk of stroke. We analyzed the risks of individual antipsychotics on various subgroups of stroke including ischemic, hemorrhagic, and other strokes, and the risks based on the antipsychotic receptor-binding profile of each drug. RESULTS:Use of any second-generation antipsychotic was associated with an increased risk of stroke (adjusted risk ratio = 1.45, P = .009) within 14 days while the use of any first-generation antipsychotic was not. Intriguingly, the use of any second-generation antipsychotic was associated with ischemic stroke but not hemorrhagic stroke. The antipsychotic receptor-binding profile analysis showed that the antihistamine 1 receptor was significantly associated with ischemic stroke (adjusted risk ratio = 1.72, P = .037), and the sensitivity analysis based on the 7-day window of exposure validated the association (adjusted risk ratio = 1.87, P = .015). CONCLUSIONS:Use of second-generation antipsychotic drugs appeared to be associated with an increased risk of ischemic stroke in the patients studied, possibly mediated by high affinity for histamine-1 receptor blockade. Further research regarding the underlying biological mechanism and drug safety is suggested.

BACKGROUND:This study assessed the risk of developing acute coronary syndrome requiring hospitalization in association with the use of certain antipsychotic medications in schizophrenia patients. METHODS:A nationwide cohort of 31,177 inpatients with schizophrenia between the ages of 18 and 65 years whose records were enrolled in the National Health Insurance Research Database in Taiwan from 2000 to 2008 and were studied after encrypting the identifications. Cases (n = 147) were patients with subsequent acute coronary syndrome requiring hospitalization after their first psychiatric admission. Based on a nested case-control design, each case was matched with 20 controls for age, sex and the year of first psychiatric admission using risk-set sampling. The effects of antipsychotic agents on the development of acute coronary syndrome were assessed using multiple conditional logistic regression and sensitivity analyses to confirm any association. RESULTS:We found that current use of aripiprazole (adjusted risk ratio [RR] = 3.68, 95% CI: 1.27-10.64, p

OBJECTIVES: Taiwanese National Health Insurance (TNHI) provides home healthcare services to patients with skilled nursing needs who were homebound or lived in nursing homes. Studies on potentially inappropriate medications (PIMs) for older home healthcare service recipients (HHSRs) are growing, but comparisons among newer criteria of PIMs have not been applied. The aim of this study was to explore the prevalence and correlates of PIMs based on three different instruments published after 2010 among older HHSRs. MATERIALS AND METHODS: We performed cross-sectional analysis of the TNHI Research Database. A total of 25,187 HHSRs aged more than 65 years in 2009 were included. Medication lists independent of chronic conditions from the 2012 Beers criteria, PIM-Taiwan criteria, and the PRISCUS (Latin for "old and venerable") criteria were used. Analysis was performed separately at patient and clinic-visit level. T-tests, chi-square analysis, and multivariate logistic regressions were used where appropriate. RESULTS: The prevalence of having at least one PIM at patient and clinic-visit level was highest with the Beers (82.67%, 36.14% respectively), followed by the PRISCUS (68.49%, 25.13%) and PIM-Taiwan (63.04%, 19.21%) criteria. At patient level, polypharmacy (odds ratio (OR) 2.53 to 4.90), higher number of clinic (OR 1.15 to 1.41), hospital (OR 1.24 to 1.64), and physician (OR 1.15 to 1.41) visits were associated with PIM use for all 3 sets of criteria. At clinic-visit level, internist/family physicians (OR 1.26 to 1.72) and neurologists/psychiatrists (OR 1.73 to 5.87) were more likely to prescribe PIMs than others. Psychotropic drugs and first generation antihistamines accounted for most of the top ten PIMs. CONCLUSION: The prevalence of PIMs was high among older Taiwanese HHSRs. Polypharmacy and certain medical specialties were associated with a higher likelihood of PIM prescriptions. Provider education and medication review and reconciliation should be considered.

BackgroundTo date there has been no large-scale international study that examined the use of clozapine in older patients with schizophrenia. This study examined the use of clozapine and its demographic and clinical correlates in older patients with schizophrenia in East Asia during the period between 2001 and 2009.MethodInformation on 1,157 hospitalized patients with schizophrenia aged 50 or older in five East Asian countries and territories (China, Hong Kong, Korea, Singapore and Taiwan) was extracted from the database of the Research on Asian Psychotropic Prescription Patterns (REAP) project. Socio-demographic and clinical characteristics and prescription of psychotropic medications were recorded.ResultsClozapine was prescribed for 20.6% of the pooled sample; 19.0% in 2001, 19.4% in 2004 and 22.9% in 2009. Multiple logistic regression analysis of the whole sample revealed that patients taking clozapine had a longer duration of illness, more negative symptoms and were less likely to receive first generation antipsychotic and anticholinergic drugs, but more likely to report weight gain compared to those not receiving clozapine. Compared to those in other sites, older patients in China were more likely to receive clozapine.ConclusionsThe prescription of clozapine for older Asian schizophrenia inpatients has remained at a stable level during the past decade. The appropriateness of use of clozapine in China needs to be further explored.

BACKGROUND: Pneumonia is one of most prevalent infectious diseases worldwide and is associated with considerable mortality. In comparison to general population, schizophrenia patients hospitalized for pneumonia have poorer outcomes. We explored the risk factors of short-term mortality in this population because the information is lacking in the literature. METHODS: In a nationwide schizophrenia cohort, derived from the National Health Insurance Research Database in Taiwan, that was hospitalized for pneumonia between 2000 and 2008 (n = 1,741), we identified 141 subjects who died during their hospitalizations or shortly after their discharges. Based on risk-set sampling in a 1∶4 ratio, 468 matched controls were selected from the study cohort (i.e., schizophrenia cohort with pneumonia). Physical illnesses were categorized as pre-existing and incident illnesses that developed after pneumonia respectively. Exposures to medications were categorized by type, duration, and defined daily dose. We used stepwise conditional logistic regression to explore the risk factors for short-term mortality. RESULTS: Pre-existing arrhythmia was associated with short-term mortality (adjusted risk ratio [RR] = 4.99, p