Incidence, prescription patterns and risk factors of antipsychotic initiation in elderly stroke survivors.

OBJECTIVES: Epidemiological data regarding antipsychotic initiation in elderly patients with stroke are limited. We aimed to investigate the incidence, prescription patterns and determinants of antipsychotic initiation in elderly patients with stroke. METHODS: We conducted a retrospective cohort study to identify patients aged above 65 years who had been admitted for stroke from the National Health Insurance Database (NHID). The index date was defined as the discharge date. The incidence and prescription pattern of antipsychotics were estimated using the NHID. To evaluate the determinants of antipsychotic initiation, the cohort identified from the NHID was linked to the Multicenter Stroke Registry (MSR). Demographics, comorbidities and concomitant medications were obtained from the NHID. Information including smoking status, body mass index, stroke severity and disability was retrieved by linking to the MSR. The outcome was antipsychotic initiation after the index date. Hazard ratios for antipsychotic initiation were estimated using the multivariable Cox model. RESULTS: In terms of prognosis, the first 2 months after a stroke was the highest-risk period for antipsychotic use. A high burden of coexisting diseases carried an increased risk of antipsychotic use; in particular, chronic kidney disease (CKD) had the highest adjusted hazard ratio (aHR = 1.73; 95% CI 1.29-2.31) as compared with other risk factors. Furthermore, stroke severity and disability were significant risk factors for antipsychotic initiation. CONCLUSIONS: Our study indicated that elderly stroke patients with chronic medical conditions, particularly CKD, and a higher stroke severity and disability were at greater risk of psychiatric disorders during the first 2 months after a stroke. CLINICAL TRIAL REGISTRATION: NA.

Sex difference in heart failure risk associated with febuxostat and allopurinol in gout patients.

Background: Gout or rapid reduction in serum uric acid level may increase the incidence of heart failure (HF). To compare the risk of HF between febuxostat and allopurinol in gout patients with coexisting cardiovascular (CV) diseases, the varying severity would be likely to confound the risk estimation. Gout and HF are both sex-related diseases, and the risk difference from the urate-lowering agents between women and men remains unknown. Aims: To evaluate the HF hospitalisations risk of febuxostat and allopurinol in gout patients in real-world settings. Methods: A population-based cohort enrolled patients with allopurinol or febuxostat initiation from 2011 to 2018. Participants were grouped into, without (low CV risk group) or with (high CV risk group) a history of recent major CV admission. The primary outcome was HF hospitalization. The secondary outcomes were composite CV events, all-cause mortality, and the cause of CV mortality. We used the 'as-treated' analysis and Cox proportional hazards model after propensity score (PS) matching. Patients were further stratified into men and women to evaluate the gender differences. Results: Febuxostat users had a significantly higher risk of HF hospitalization than allopurinol users in gout patients either with low CV risk [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.25-1.55] or high CV risk [HR 1.36; 95% CI 1.22-1.52]. Particularly, women with gout had a higher risk of HF hospitalization than men. Conclusion: The HF hospitalization risk was highest in gout women with high CV risk and febuxostat use. Monitoring of HF is warranted in these patients.

Comparative safety of antipsychotic medications in elderly stroke survivors: A nationwide claim data and stroke registry linkage cohort study.

BACKGROUND: Antipsychotics remain the first choice of treatment for post-stroke psychosis, despite an increased risk of mortality reported in elderly patients. We aimed to compare the mortality risk among antipsychotics in elderly patients with stroke using the stroke registry for external adjustment. METHODS: We conducted a retrospective cohort study to identify patients aged above 65 years who were admitted for stroke in the National Health Insurance Database (NHID) from 2002 to 2014. The first date of antipsychotic use after the stroke hospitalization was defined as the index date. Covariates including diseases, medications and external information on smoking, BMI, stroke severity and disability, that were unavailable in the NHID were obtained from the linked Multicenter Stroke Registry (MSR) and used for propensity score calibration (PSC). The main outcome was one-year all-cause mortality. RESULTS: Stroke patients in the NHID prescribed with haloperidol, quetiapine and risperidone numbered 22,235, 28,702 and 8 663, respectively. In the PSC-adjusted analyses, haloperidol [adjusted hazard ratio (aHR) = 1.22; 95% CI 1.18-1.27] and risperidone (aHR = 1.31; 95% CI 1.24-1.38) users had a higher mortality risk than quetiapine users. When the dosage was higher than 0.5 defined daily dose (DDD), haloperidol and risperidone users had a significant mortality risk as compared with those taking a lower dose. CONCLUSIONS: In post-stroke elderly patients, quetiapine would pose less mortality risk than risperidone and haloperidol at doses higher than 0.5 DDD. When haloperidol or risperidone is indicated, starting with a lower dose is suggested to avoid excess risk.

Risk of age-related macular degeneration in aspirin users and non-aspirin users: A population-based cohort study in Taiwan.

BACKGROUND: The association between cardioprotective aspirin and risk of age-related macular degeneration (AMD) is still controversial up to date. We aimed to analyze the risk of AMD between aspirin users and non-aspirin users. METHOD: This was a retrospective cohort study by using claims data from the National Health Insurance Research Database. Patients aged more than 45 years old who initiated aspirin during 2002 to 2012 were followed till 2013. We first selected an age and sex-matched cohort, then identified aspirin users and non-aspirin users as propensity score-matched cohort. Cox proportional hazard regression model was applied to compare their hazards and 95% confidence intervals. Incidence of newly developed AMD, neovascular AMD, and other-AMD was calculated. RESULTS: We identified 204 085 regular aspirin users and 478 048 non-aspirin users from our datasets. The univariate HR was 2.85 (95% CI, 2.75-2.96), and the multivariate HR was 2.54 (95% CI, 2.44-2.65). In the PS-matched cohort, the HR was 2.38 (95% CI, 2.25-2.52). The incidence of aspirin users for AMD risk was 11.95 per 1000 person-year, while the incidence of non-aspirin users was only 3.92 per 1000 person-year. CONCLUSION: Patients with regular use of aspirin had higher risk in developing AMD compared to non-aspirin users and suggest to have regular visual acuity and funduscopic examination.

Not all aspirin products have equivalent antiplatelet efficacy-Aspirin formulated with magnesium stearate is less effective in preventing ischemic stroke.

PURPOSE: Magnesium stearate (MgSt) is a widely used excipient in pharmaceutical formulations but should be avoided in aspirin preparations as it hydrolyzes aspirin. We hypothesized that preparations of aspirin-containing MgSt (MgSt-ASA) are less effective in preventing thrombosis in clinical settings. The risk of composite cardiovascular events in patients treated with MgSt-ASA preparations for preventing secondary stroke was evaluated. METHODS: This retrospective cohort study used Taiwan's claims data from 1997 to 2013. Patients who were discharged after ischemic stroke (IS) and administered with only MgSt-ASA or non-MgSt-ASA preparations were enrolled. Composite events including all-cause mortality, IS hospitalization, and myocardial infarction-related hospitalization in the follow-up period under therapy with MgSt-ASA or non-MgSt-ASA preparations were considered primary outcomes. Hazard ratios (HRs) were adjusted with the baseline comorbidities and medications using the Cox model. RESULTS: A total of 19 500 patients with IS (60% males, average age 67 years) were identified, which included 2064 patients receiving MgSt-ASA treatment initially and 17 436 patients receiving non-MgSt-ASA preparation initially. The crude incidence of composite events was 11.65 per 100 person-years, whereas it was 11.45 and 13.90 per 100 person-years for patients receiving non-MgSt-ASA and MgSt-ASA treatments, respectively. The risk of composite events was higher in patients receiving MgSt-ASA preparations than in those receiving non-MgSt-ASA formulations, with the adjusted HR being 1.23 at 95% confidence interval of 1.02 to 1.47. CONCLUSIONS: MgSt-ASA preparation use was associated with a higher risk of composite events than non-MgSt-ASA preparations. Review of aspirin formulations under regulatory intervention is warranted.

Practice Pattern of Hepatitis B Testing in Rheumatoid Arthritis Patients: A Cross-National Comparison Between the US and Taiwan.

OBJECTIVE: The hepatitis B virus (HBV) testing rates and patterns in rheumatoid arthritis (RA) patients starting disease-modifying antirheumatic drugs (DMARDs) have not been well studied. We describe and compare the practice patterns of HBV testing among RA patients in the US and Taiwan. METHODS: We conducted a retrospective cohort study, including RA patients starting a first DMARD in the US or Taiwan. The first date patients newly received any DMARD was defined as the index date, and the 1-year period before the index date was the baseline period. HBV testing was defined as any of the following tests 1 year before or after the index date: hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody, hepatitis B envelope antigen, hepatitis B envelope antibody, or HBV DNA. We calculated the HBV testing rate by year and used Poisson regression to calculate the testing rate ratio. RESULTS: We identified 14,568 RA patients in the US and 46,265 in Taiwan. The overall testing rate was 20.3% in the US and 24.5% in Taiwan, and gradually increased over the study period from 13.1-23.0% in the US and 16.8-30.0% in Taiwan. More than one type of HBV test was used in 43.4% of patients in the US and 16.3% of patients in Taiwan receiving tests. Results of Poisson regression found Taiwan had a 17% higher testing rate over the US during the followup period (crude rate ratio 1.17 [95% confidence interval 1.12-1.22]). CONCLUSION: We found small differences in the HBV testing rates across the US and Taiwan. Although the rate gradually increased in the past decade, it remained low in both countries.

Validation of a novel claims-based stroke severity index in patients with intracerebral hemorrhage.

BACKGROUND: Stroke severity is an important outcome predictor for intracerebral hemorrhage (ICH) but is typically unavailable in administrative claims data. We validated a claims-based stroke severity index (SSI) in patients with ICH in Taiwan. METHODS: Consecutive ICH patients from hospital-based stroke registries were linked with a nationwide claims database. Stroke severity, assessed using the National Institutes of Health Stroke Scale (NIHSS), and functional outcomes, assessed using the modified Rankin Scale (mRS), were obtained from the registries. The SSI was calculated based on billing codes in each patient's claims. We assessed two types of criterion-related validity (concurrent validity and predictive validity) by correlating the SSI with the NIHSS and the mRS. Logistic regression models with or without stroke severity as a continuous covariate were fitted to predict mortality at 3, 6, and 12 months. RESULTS: The concurrent validity of the SSI was established by its significant correlation with the admission NIHSS (r = 0.731; 95% confidence interval [CI], 0.705-0.755), and the predictive validity was verified by its significant correlations with the 3-month (r = 0.696; 95% CI, 0.665-0.724), 6-month (r = 0.685; 95% CI, 0.653-0.715) and 1-year (r = 0.664; 95% CI, 0.622-0.702) mRS. Mortality models with NIHSS had the highest area under the receiver operating characteristic curve, followed by models with SSI and models without any marker of stroke severity. CONCLUSIONS: The SSI appears to be a valid proxy for the NIHSS and an effective adjustment for stroke severity in studies of ICH outcome with administrative claims data.

Comparative persistence of antiepileptic drugs in patients with epilepsy: A STROBE-compliant retrospective cohort study.

We compared persistence of antiepileptic drugs (AEDs) including carbamazepine, oxcarbazepine, gabapentin, lamotrigine, topiramate, valproic acid, and phenytoin in an Asian population with epilepsy.A retrospective cohort study was conducted by analyzing Taiwan's National Health Insurance Research Database (NHIRD). Adult epilepsy patients newly prescribed with AEDs between 2005 and 2009 were included. The primary outcome was persistence, defined as the treatment duration from the date of AED initiation to the date of AED discontinuation, switching, hospitalization due to seizure or disenrollment from databases, whichever came first. Cox proportional hazard models were used to estimate the risk of non-persistence with AEDs.Among the 13,061 new users of AED monotherapy (mean age: 58 years; 60% men), the persistence ranged from 218.8 (gabapentin) to 275.9 (oxcarbazepine) days in the first treatment year. The risks of non-persistence in patients receiving oxcarbazepine (adjusted hazard ratio [HR], 0.78; 95% CI, 0.74-0.83), valproic acid (0.88; 0.85-0.92), lamotrigine (0.72; 0.65-0.81), and topiramate (0.90; 0.82-0.98) were significantly lower than in the carbamazepine group. Compared with carbamazepine users, the non-persistence risk was higher in phenytoin users (1.10; 1.06-1.13), while gabapentin users (1.03; 0.98-1.09) had similar risk. For risk of hospitalization due to seizure and in comparison with carbamazepine users, oxcarbazepine (0.66; 0.58-0.74) and lamotrigine (0.46; 0.35-0.62) users had lower risk, while phenytoin (1.35; 1.26-1.44) users had higher risk. The results remained consistent throughout series of sensitivity and stratification analyses.The persistence varied among AEDs and was better for oxcarbazepine, valproic acid, lamotrigine, and topiramate, but worse for phenytoin when compared with carbamazepine.

Proton pump inhibitors and risk of Clostridium difficile infection: a multi-country study using sequence symmetry analysis.

OBJECTIVE: To determine the association between incident proton pump inhibitor (PPI) use and Clostridium difficile infections across multiple countries Method: National data covering the total population in Australia and Korea, the Canadian population over 65 years and a 3 million person random sample data set from Taiwan were assessed, as were data from a worker insurance population and a hospital inpatient/outpatient population in Japan. Sequence symmetry analysis was used to assess the association with oral vancomycin dispensing as the outcome of interest. RESULTS: 54,957 patients were included. Positive associations were observed in Australia; adjusted sequence ratio (ASR) 2.48 (95% CI 1.90, 3.12), Korea ASR 2.15 (95%CI 2.11, 2.19), Canada ASR 1.45 (95% CI 1.16, 1.79), Japan hospital dataset ASR 3.21 (95%CI 2.12, 4.55) and Japan worker insurance dataset ASR 5.40 (95% CI 2.73, 8.75). The pooled result was ASR 2.40 (95%CI 1.88, 3.05) and 3.16 (95%CI 1.95, 5.10) when limited to Japan, Korean and Taiwan. Results did not vary by individual PPI. The temporal analysis showed effects within the first two weeks of PPI initiation. CONCLUSION: Our study confirms the association between PPI initiation and C. difficile infections across countries in the Asia-Pacific region.

Validation of algorithms to identify stroke risk factors in patients with acute ischemic stroke, transient ischemic attack, or intracerebral hemorrhage in an administrative claims database.

BACKGROUND: Stroke patients have a high risk for recurrence, which is positively correlated with the number of risk factors. The assessment of risk factors is essential in both stroke outcomes research and the surveillance of stroke burden. However, methods for assessment of risk factors using claims data are not well developed. METHODS: We enrolled 6469 patients with acute ischemic stroke, transient ischemic attack, or intracerebral hemorrhage from hospital-based stroke registries, which were linked with Taiwan's National Health Insurance (NHI) claims database. We developed algorithms using diagnosis codes and prescription data to identify stroke risk factors including hypertension, diabetes, hyperlipidemia, atrial fibrillation (AF), and coronary artery disease (CAD) in the claims database using registry data as reference standard. We estimated the kappa statistics to quantify the agreement of information on the risk factors between claims and registry data. RESULTS: The prevalence of risk factors in the registries was hypertension 77.0%, diabetes 39.1%, hyperlipidemia 55.6%, AF 10.1%, and CAD 10.9%. The highest kappa statistics were 0.552 (95% confidence interval 0.528-0.577) for hypertension, 0.861 (0.836-0.885) for diabetes, 0.572 (0.549-0.596) for hyperlipidemia, 0.687 (0.663-0.712) for AF, and 0.480 (0.455-0.504) for CAD. Algorithms based on diagnosis codes alone could achieve moderate to high agreement in identifying the selected risk factors, whereas prescription data helped improve identification of hyperlipidemia. CONCLUSIONS: We tested various claims-based algorithms to ascertain important risk factors in stroke patients. These validated algorithms are useful for assessing stroke risk factors in future studies using Taiwan's NHI claims data.

Hypotension Associated With Intravitreal Bevacizumab Therapy for Retinopathy of Prematurity.

Intravitreal bevacizumab therapy in preterm infants for retinopathy of prematurity (ROP) can be associated with hypotension. We report twin preterm infants who developed hypotension within 1 day after intravitreal bevacizumab therapy for ROP. Before receiving the medication, their clinical statuses were stable and similar. The dose, procedure, and premedication were the same; however, twin B presented with hypotension for 3 days. Although bevacizumab-related hypotension has been described in product information (incidence rate 7%-15%), this is the first case report of intravitreal bevacizumab for ROP inducing hypotension. Physicians should be aware of intravitreal bevacizumab therapy-related hypotension when treating ROP. We suggest conducting a postmarketing active surveillance on the systemic adverse effects of this regimen in preterm infants.

Validity of in-hospital mortality data among patients with acute myocardial infarction or stroke in National Health Insurance Research Database in Taiwan.

OBJECTIVE: The aim of this study was to determine the validity of in-hospital mortality records in the National Health Insurance Research Database (NHIRD) by cross-comparing with death records from the electronic medical records (EMR) of a medical center in southern Taiwan. METHODS: Data on patients admitted to the medical center for acute myocardial infarction (AMI) or stroke during the years 2005 to 2010 were extracted from the two databases and cross-linkages with patients' characteristics (birth date, gender, admission date, and discharge date). While the death record was available in the catastrophic illness registry data files (CIRD), we also estimated the insurance status and death record in the CIRD subset using confirmed death cases. Additionally, agreement in comorbidities between records from the two databases was evaluated. RESULTS: A total of 6197 cases were successfully linked, with a linkage rate of 96.56% of cases in the NHIRD when linked to those from the EMR. Among the linked population, 538 of 682 patients retrieved as expired in the NHIRD were also so recorded in the EMR. This yielded a positive predictive value of 0.79 when the EMR was used as the gold standard. Patients having death records in both the CIRD subset and the EMR totaled 364, which yielded a percentage positive agreement rate of 76%. The consistency in comorbidity diagnoses between the two databases was more than 90% among matched cases. CONCLUSIONS: The accuracy of death records in the NHIRD was high, and appears to be a valid resource for population research in cardiovascular diseases.

Brief Report: Databases in the Asia-Pacific Region: The Potential for a Distributed Network Approach.

BACKGROUND: This study describes the availability and characteristics of databases in Asian-Pacific countries and assesses the feasibility of a distributed network approach in the region. METHODS: A web-based survey was conducted among investigators using healthcare databases in the Asia-Pacific countries. Potential survey participants were identified through the Asian Pharmacoepidemiology Network. RESULTS: Investigators from a total of 11 databases participated in the survey. Database sources included four nationwide claims databases from Japan, South Korea, and Taiwan; two nationwide electronic health records from Hong Kong and Singapore; a regional electronic health record from western China; two electronic health records from Thailand; and cancer and stroke registries from Taiwan. CONCLUSIONS: We identified 11 databases with capabilities for distributed network approaches. Many country-specific coding systems and terminologies have been already converted to international coding systems. The harmonization of health expenditure data is a major obstacle for future investigations attempting to evaluate issues related to medical costs.

Variation in Association Between Thiazolidinediones and Heart Failure Across Ethnic Groups: Retrospective analysis of Large Healthcare Claims Databases in Six Countries.

INTRODUCTION: The prevalence of polymorphisms among the metabolising enzymes and pharmacodynamic receptors relevant for the thiazolidinediones differs by ethnic group, a factor that may modify risk of adverse drug events. OBJECTIVE: The aim of the study was to determine if the risk of oedema or heart failure associated with the thiazolidinediones varies in populations in Australia, Canada, Hong Kong, Japan, Korea and Taiwan. METHODS: Sequence symmetry analyses were undertaken to investigate the risk of peripheral oedema, as measured by incident furosemide dispensing, and risk of hospitalisations for heart failure. Results were pooled, with Australia and Canada representing predominantly Caucasian population and all other countries contributing to Asian population estimates. RESULTS: Pooled estimates of risk for furosemide initiation in the Caucasian populations were significantly increased for pioglitazone [adjusted sequence ratio (ASR) 1.47; 95 % confidence interval (CI) 1.14-1.91] and rosiglitazone (ASR 1.65; 95 % CI 1.58-1.72), while in the Asian populations, the pooled risk estimates were lower (ASR 1.11; 95 % CI 0.93-1.32 and ASR 1.21; 95 % CI 1.01-1.45 for pioglitazone and rosiglitazone, respectively). Results for hospitalisation for heart failure showed a similar trend, with elevated risk in the Australian data (ASR 1.88; 95 % CI 1.01-3.5 and ASR 1.25; 95 % CI 0.76-2.05 for pioglitazone and rosiglitazone, respectively), while no increased risk was found in the pooled results for the Asian populations. CONCLUSION: The risk of both oedema and heart failure with thiazolidinediones was higher in predominantly Caucasian countries than in the Asian countries assessed. Assessment of adverse events by ethnicity may support safer medicine use.

Dementia Increases Severe Sepsis and Mortality in Hospitalized Patients With Chronic Obstructive Pulmonary Disease.

Dementia increases the risk of morbidity and mortality in hospitalized patients. However, information on the potential effects of dementia on the risks of acute organ dysfunction, severe sepsis and in-hospital mortality, specifically among inpatients with chronic obstructive pulmonary disease (COPD), is limited. The observational analytic study was inpatient claims during the period from 2000 to 2010 for 1 million people who were randomly selected from all of the beneficiaries of the Taiwan National Health Insurance in 2000. In total, 1406 patients with COPD and dementia were admitted during the study period. Hospitalized patients with COPD and free from a history of dementia were randomly selected and served as control subjects (n = 5334). The patient groups were matched according to age (±3 years), gender, and the year of admission, with a control/dementia ratio of 4. Only the first-time hospitalization data for each subject was analyzed. Logistic regression models were used to calculate the odds ratio (OR) of outcome measures (acute organ dysfunction, severe sepsis, and mortality), controlling for confounding factors (age, sex, comorbidity, infection site, hospital level, and length of stay). In COPD patients with dementia, the incidence rate of severe sepsis and hospital mortality was 17.1% and 4.8%, respectively, which were higher than the controls (10.6% and 2.3%). After controlling for potential confounding factors, dementia was found to significantly increase the odds of severe sepsis and hospital mortality with an adjusted OR (OR) of 1.38 (95% confidence interval [CI] 1.10-1.72) and 1.69 (95% CI 1.18-2.43), respectively. Dementia was also significantly associated with an increased OR of acute respiratory dysfunction (adjusted OR 1.39, 95% CI 1.09-1.77). In hospitalized COPD patients, the presence of dementia may increase the risks of acute respiratory dysfunction, severe sepsis, and hospital mortality, which warrants the attention of health care professionals.

Utilization of oral antidiabetic medications in Taiwan following strategies to promote access to medicines for chronic diseases in community pharmacies.

OBJECTIVES: Taiwan's National Health Insurance (NHI) has encouraged physicians to use "chronic medication prescriptions" for patients with stable chronic diseases since 1995. Patients are allowed to refill such prescriptions at community pharmacies for a maximum of three months' supply of medications without revisiting the doctor. In 2006, NHI initiated strategies targeting the public, doctors, and healthcare facilities to enhance the overall rate of chronic medication prescriptions, aiming to achieve 30% by 2010. We examined prescribing and dispensing of oral antidiabetic drugs from 2001 to 2010, before and after the start of the promotion strategies for chronic medication prescriptions in 2006. METHODS: Using outpatient care data from the NHI database and the interrupted time series design, we analyzed changes in rate of chronic medication prescriptions, share of prescriptions filled at community pharmacies, and share of reimbursed expenditures accounted by community pharmacies. RESULTS: During 2001-2010, the rate of chronic medication prescriptions for diabetes increased steadily by about 3% per year (from 3.5% to 26.2%). Three years after the promotion strategies, there was a non-significant reduction of 8.7% (95% confidence interval [CI]: -17.35%, 0.05%) in the rate of chronic medication prescriptions but increases in prescription refills at community pharmacies and associated reimbursed expenditures: 12.8% (95% C.I.:1.66%, 23.98%) and 15.8% (95% C.I.: -1.35%, 33.02%) respectively. CONCLUSIONS: While rate of chronic medication prescriptions was not significantly affected by the 2006 promotion strategy, shares of prescriptions refilled at community pharmacies and associated expenditures increased slightly but significantly.