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.

Use of spatial panel-data models to investigate factors related to incidence of end-stage renal disease: a nationwide longitudinal study in Taiwan.

BACKGROUND: The assumptions of conventional spatial models cannot estimate the responses across space and over time. Here we propose new spatial panel data models to investigate the association between the risk factors and incidence of end-stage renal disease (ESRD). METHODS: A longitudinal (panel data) study was conducted using data from the National Health Insurance Database in Taiwan. We developed an algorithm to identify the patient's residence and estimate the ESRD rate in each township. Corresponding covariates, including patient comorbidities, history of medication use, and socio-environmental factors, were collected. Local Indicators of Spatial Association were used to describe local spatial clustering around an individual location. Moreover, a spatial panel data model was proposed to investigate the association between ESRD incidence and risk factors. RESULTS: In total, 73,995 patients with ESRD were included in this study. The western region had a higher proportion of high incidence rates than the eastern region. The proportion of high incidence rates in the eastern areas increased over the years. We found that most "social environmental factors," except average income and air pollution (PM 2.5 and PM10), had a significant influence on the incidence rate of ESRD when considering spatial dependences of response and explanatory variables. Receiving non-steroidal anti-inflammatory drugs and aminoglycosides within 90 days prior to ESRD had a significant positive effect on the ESRD incidence rate. CONCLUSION: Future comprehensive studies on townships located in higher-risk clusters of ESRD will help in designing healthcare policies for suitable action.

Reducing Medication Errors by Adopting Automatic Dispensing Cabinets in Critical Care Units.

Medication errors can have severe consequences and threaten patient safety. The patient safety-related benefits of automated dispensing cabinets (ADCs) have been reported by several previous studies, including a reduction in medication errors in intensive care units (ICUs) and emergency departments. However, the benefits of ADCs need to be assessed, given the different healthcare practice models. This study aimed to compare the rates of medication errors, including prescription, dispensing, and administrative, before and after using ADCs in intensive care units. The prescription, dispensing, and administrative error data before and after the adoption of ADCs were retrospectively collected from the medication error report system. The severity of medication errors was classified according to the National Coordinating Council for Medication Error Reporting and Prevention guidelines. The study outcome was the rate of medication errors. After the adoption of ADCs in the intensive care units, the rates of prescription and dispensing errors reduced from 3.03 to 1.75 per 100,000 prescriptions and 3.87 to 0 per 100,000 dispensations, respectively. The administrative error rate decreased from 0.046 to 0.026%. The ADCs decreased National Coordinating Council for Medication Error Reporting and Prevention category B and D errors by 75% and category C errors by 43%. To improve medication safety, multidisciplinary collaboration and strategies, such as the use of automated dispensing cabinets, education, and training programs from a systems perspective, are warranted.

The Impact of Sildenafil on Ischemic Outcomes in Patients with Pulmonary Hypertension - A Nationwide Cohort Study.

Background: Sildenafil, a phosphodiesterase-5 inhibitor, has been approved for the treatment of pulmonary hypertension (PH). It improves exercise capacity, symptoms and hemodynamics in patients with PH by lowering pulmonary pressures. Preclinical studies have indicated a possible protective effect of sildenafil on ischemia/reperfusion injury. Nevertheless, evidence showing the impact of sildenafil on ischemic disorders in patients with PH is lacking. Methods: Using the Taiwanese National Health Insurance Research Database and Cause of Death databases, we conducted a retrospective cohort study to investigate the hazard ratio (HR) with inverse probability of treatment weighting (IPTW) of sildenafil for the development of major adverse cardiovascular and cerebrovascular events (MACCEs), including new-onset acute myocardial infarction (AMI) and ischemic stroke in patients with PH. The follow-up period was 7 years. In addition, we performed sensitivity analysis by limiting the studied population to those who received right heart catheterization and excluding those with a history of coronary arterial disease. Results: After adjusting for age, sex and comorbidities, the patients receiving sildenafil had a significantly lower risk of subsequent AMI [adjusted HR with IPTW: 0.42; confidence interval (CI): 0.20-0.86] and a trend of less ischemic stroke (adjusted HR with IPTW: 0.72; CI: 0.51-1.02). Interestingly, among the sildenafil users, those who were older, had chronic kidney disease, and took cardiovascular medications showed the most significant reductions in the risk of MACCEs. The sensitivity analysis showed similar results. Conclusions: The use of sildenafil in patients with PH was associated with a lower risk of long-term MACCEs. More evidence is needed to validate our findings.

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.

Detecting Potential Adverse Drug Reactions Using a Deep Neural Network Model.

BACKGROUND: Adverse drug reactions (ADRs) are common and are the underlying cause of over a million serious injuries and deaths each year. The most familiar method to detect ADRs is relying on spontaneous reports. Unfortunately, the low reporting rate of spontaneous reports is a serious limitation of pharmacovigilance. OBJECTIVE: The objective of this study was to identify a method to detect potential ADRs of drugs automatically using a deep neural network (DNN). METHODS: We designed a DNN model that utilizes the chemical, biological, and biomedical information of drugs to detect ADRs. This model aimed to fulfill two main purposes: identifying the potential ADRs of drugs and predicting the possible ADRs of a new drug. For improving the detection performance, we distributed representations of the target drugs in a vector space to capture the drug relationships using the word-embedding approach to process substantial biomedical literature. Moreover, we built a mapping function to address new drugs that do not appear in the dataset. RESULTS: Using the drug information and the ADRs reported up to 2009, we predicted the ADRs of drugs recorded up to 2012. There were 746 drugs and 232 new drugs, which were only recorded in 2012 with 1325 ADRs. The experimental results showed that the overall performance of our model with mean average precision at top-10 achieved is 0.523 and the rea under the receiver operating characteristic curve (AUC) score achieved is 0.844 for ADR prediction on the dataset. CONCLUSIONS: Our model is effective in identifying the potential ADRs of a drug and the possible ADRs of a new drug. Most importantly, it can detect potential ADRs irrespective of whether they have been reported in the past.

Cardiovascular and Bleeding Risks in Acute Myocardial Infarction Newly Treated With Ticagrelor vs. Clopidogrel in Taiwan.

BACKGROUND: There are few data on ticagrelor in Asian patients. This study evaluated clinical outcomes with ticagrelor and clopidogrel in Taiwanese patients with acute myocardial infarction (AMI).Methods and Results:We used the Taiwan National Health Insurance Research Database to identify 27,339 AMI patients aged ≥18 years between January 2012 and December 2014, and only patients who survived greater than or equal to 30 days after AMI and took dual antiplatelet therapy were included. Cohorts of ticagrelor and clopidogrel were matched 1:8, based on propensity score matching, to balance baseline covariates. The primary efficacy endpoints were death from any cause, AMI, or stroke. The safety endpoints consisted of major gastrointestinal bleeding or intracerebral hemorrhage. Following propensity matching, the primary efficacy endpoint rate was 22% lower in the ticagrelor group than in the clopidogrel group (10.6% and 16.2%, respectively; adjusted HR, 0.779; 95% CI: 0.684-0.887). The safety endpoint rate was similar between the ticagrelor and clopidogrel groups (3.2% and 4.1% respectively; adjusted HR, 0.731; 95% CI: 0.522-1.026). CONCLUSIONS: In real-world AMI Taiwanese patients, ticagrelor seemed to offer better anti-ischemic protection than clopidogrel, without an increase in the rate of major bleeding. A large-scale randomized trial is needed to assess the efficacy and safety of ticagrelor in East Asian AMI patients.

Pay for performance program reduces treatment needed diabetic retinopathy - a nationwide matched cohort study in Taiwan.

BACKGROUND: Pay-for-Performance programs have shown improvement in indicators monitoring adequacy and target achievement in diabetic care. However, less is known regarding the impact of this program on the occurrence and long-term effects of diabetic retinopathy. The objective of this study was to determine the effect of pay-for-performance program on the development of treatment needed for diabetic retinopathy in type 2 diabetes patients. METHODS: We conducted a nationwide retrospective cohort study with a matching design using the Taiwan National Health Insurance Research Database from 2000 to 2012. The outcome was defined as the treatment needed diabetic retinopathy. We matched Pay-for-Performance and non-Pay-for-Performance groups for age, gender, year diabetes was diagnosed and study enrollment, and duration of follow-up. RESULTS: A total of 9311 patients entered the study cohort, of whom 2157 were registered in the Pay-for-Performance group and 7154 matched in the non-Pay-for-Performance group. The incidence of treatment needed diabetic retinopathy was not significantly different in two groups. However, the incidence of treatment needed diabetic retinopathy was significantly different if restricted the non-Pay-for-Performance group who had at least 1 eye examination or optical coherence tomography within 1 year (adjusted hazard ratio, 0.78; 95% confidence interval, 0.64-0.94). CONCLUSIONS: Pay-for-Performance is valuable in preventing the development of treatment needed diabetic retinopathy, which could be attributed to the routine eye examination required in the Pay-for-Performance program. We could improve our diabetic care by promoting eye health education and patient awareness on the importance of regular examinations.

Risks of newly onset hemorrhagic stroke in patients with neovascular age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is an eye disease causing blindness in the elderly. It shares many common possible pathogenic mechanisms with cardiovascular diseases. Many studies have discussed the association between AMD and stroke, but the results were inconsistent. Our aim was to determine the associations between neovascular AMD and the risk of stroke in the Taiwanese population. METHODS: This is a retrospective cohort study. We used claims data from National Health Insurance Research Database. Patients aged more than 45 years without stroke, myocardial infarction, or any AMD were selected from 2001 to 2008 and followed until 2010. The index date was defined as the date of nAMD diagnosis (ICD-9 code, 362.52). The comparison group was patients without an nAMD diagnosis with age- and sex-matched to nAMD subjects at a ratio of up to 10 to 1. Kaplan-Meier survival analysis and Cox regression analysis were used. The incidence of stroke events (ICD-9 codes, 430-434) and their subtypes (hemorrhagic and ischemic) were primary outcomes. Secondary outcomes included acute myocardial infarction (AMI), composite AMI/stroke, and all-cause mortality. RESULTS: Patients with nAMD had a higher risk of developing stroke, with an adjusted HR of 1.30 (95% CI, 1.01-1.68). A higher risk for hemorrhagic stroke (HR, 1.70, 95% CI, 1.03-2.83) was also found. No significant differences were observed in ischemic stroke, the composite of AMI/stroke, and all-cause mortality. CONCLUSIONS: Patients with nAMD had a significantly higher risk of developing stroke, which was driven mainly by the increased risk of developing the hemorrhagic subtype.

Statin Adherence After Ischemic Stroke or Transient Ischemic Attack Is Associated With Clinical Outcome.

BACKGROUND: Statin therapy is beneficial for ischemic stroke patients, but little is known about whether statin adherence affects clinical outcome. We therefore evaluated the effect of statin adherence in patients with ischemic stroke or transient ischemic attack (TIA). METHODS AND RESULTS: From Taiwan Bureau of National Health Insurance database, we enrolled patients with no prior statin therapy admitted for ischemic stroke or TIA between January 2002 and December 2005. Patients were grouped based on statin adherence according to medication possession ratio (MPR): good adherence (MPR >80%; n=2,274), intermittent adherence (MPR=40-80%; n=3,710), and poor adherence (MPR <40%; n=9,424). The study endpoint was the composite outcome of recurrent ischemic stroke, hemorrhagic stroke, and acute coronary event 1 year after statin initiation. Follow-up data were obtained through December 2010. During follow-up, composite endpoints occurred in 5,354 patients (34.7%): good adherence, 798 patients (35.1%); intermittent adherence, 1,338 patients (36.1%); and poor adherence, 3,218 patients (34.1%). Compared with the good adherence group, patients in the poor adherence group and intermittent adherence group had higher risk of worse clinical outcome (adjusted HR, 1.26 and 1.16, respectively; 95% CI: 1.17-1.37 and 1.07-1.27, respectively). CONCLUSIONS: Good statin adherence was associated with better clinical outcome in patients with acute ischemic stroke or TIA. (Circ J 2016; 80: 731-737).

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.

Hormone therapy and risk of venous thromboembolism among postmenopausal women in Taiwan - a 10-year nationwide population-based study.

BACKGROUND: The incidence of venous thromboembolism (VTE) in Asians is lower than in Caucasians, but the risk of VTE associated with hormone therapy (HT) in Taiwanese postmenopausal women has not been determined. METHODS AND RESULTS: From Taiwan's National Health Insurance Research Database, we established matched cohorts (HT users and nonusers) of postmenopausal women aged ≥50 years between 1 January 1998 and 31 December 2008. We calculated the 2-year incidence of VTE in HT users and nonusers. HT users and nonusers were matched 1:1 based on propensity-score matching. Cox regression hazard model was used to identify risk factors of VTE. We initially identified 499,594 HT users and 424,963 nonusers. There were higher percentages of cancer and cardiovascular events among the HT nonusers. After matching, the VTE incidence was 4.4 vs. 2.6 per 10,000 patient-years (adjusted hazard ratio 1.796, 95% confidence interval 1.272-2.537) in HT users and nonusers, respectively. The Cox regression hazard model showed that HT use, older age, malignancy, heart failure, and recent major surgery were independent risk factors for VTE. CONCLUSIONS: Although the incidence of VTE was very low among this cohort of Taiwanese postmenopausal women, oral HT was still associated with an increased risk of VTE. Therefore, physicians should be aware of other potential VTE risk factors when prescribing oral HT to postmenopausal women.

Effects of safety warnings and risk management plan for Thiazolidinediones in Taiwan.

PURPOSE: To evaluate changes in thiazolidinedione use and quality of prescription following safety warnings for thiazolidinediones and cardiac risk in 2007, Risk Management Plan (RMP) policy for rosiglitazone in 2010, and warning for pioglitazone and bladder cancer risk in 2010 in Taiwan. METHODS: We obtained 2003-2011 claims data from Taiwan's National Health Insurance Research Database. Using an interrupted time series design and segmented regression, we estimated changes in monthly prescribing rates for thiazolidinediones among all and prevalent diabetes patients with and without cardiovascular disease history (CV history). We also compared time to prescription of thiazolidinediones among new diabetes patients with CV history before and after each regulatory action using survival analysis. RESULTS: Among prevalent patients with and without CV history, the prescribing rates of rosiglitazone decreased 36.88% and 28.92% after safety warnings in 2007 respectively. Pioglitazone prescriptions increased 13% among patients with CV history, but no changes were detected among patients without CV history. After rosiglitazone's RMP policy in 2010, large reductions in prescriptions were observed in patients with CV history (-101.67%) and those without CV history (-88.04%). Among new diabetes patients with CV history, cardiac safety warnings in 2007 significantly delayed the prescription of rosiglitazone, but no significant change was found for pioglitazone. CONCLUSIONS: The Taiwan FDA regulatory actions for thiazolidinediones communicated possible risks of cardiac events and bladder cancer. Different safety regulatory actions had differential impacts on the use of rosiglitazone and pioglitazone and the quality use of these drugs among the high-risk patients.

An investigation of the potential association between retinal detachment and oral fluoroquinolones: a self-controlled case series study.

OBJECTIVES: A study reported a significant association between oral fluoroquinolones and the development of retinal detachment among current users of oral fluoroquinolones (Etminan M, Forooghian F, Brophy JM et al. JAMA 2012; 307: 1414-9). However, other published studies have discordant results. This study aimed to investigate this association and to estimate the absolute risk of developing retinal detachment in patients exposed to oral fluoroquinolones. METHODS: A self-controlled case series study was conducted with data retrieved from the Hong Kong Clinical Data Analysis and Reporting System database and the Taiwan National Health Insurance Research Database. Hong Kong and Taiwanese patients who had prescriptions for oral fluoroquinolones and a procedure for retinal detachment between 2001 and 2012 and between 2000 and 2010, respectively, were defined as cases and included in the analysis. RESULTS: A total of 9 events were found during the fluoroquinolone-exposed period and 1407 events were found during the non-exposed period. The adjusted incidence rate ratio in the combined model was 1.26 (0.65-2.47). The crude absolute risk of experiencing retinal detachment whilst on oral fluoroquinolones was ∼1.3 per 200 000 prescriptions. CONCLUSIONS: Our study does not support the association between the use of fluoroquinolones and the development of retinal detachment and our findings are strikingly similar to that of the study conducted in Denmark. Doubt is cast on the association between the use of fluoroquinolones and the development of retinal detachment. Therefore, the use of fluoroquinolones should not be precluded based on the current evidence on the risk of retinal detachment. The impact of different ethnicities on the response to fluoroquinolones should also be investigated.

A retrospective study on the usage of cough and cold medications in viral respiratory tract infections in Taiwanese children.

OBJECTIVE: We sought to describe the epidemiology of viral respiratory-tract infections and patterns in prescriptions of cough and cold medications among young children who were suffering from viral respiratory tract infections (vRTIs). METHODS: We conducted a cross-sectional study to examine vRTI-episode occurrence and cold-medication utilization in outpatients in 2007 using the National Health Insurance Research Database (NHIRD) in Taiwan. One-third of the children under 12 years of age who had at least one outpatient visit for a vRTI as randomly selected from NHIRD were included in the analysis. RESULTS: A total of 895,942 children had a diagnosis of vRTI (6,144,336 visits) during 2007, 58% of whom were aged 6 to 12 years, and 52% of whom were male. The mean cumulative incidence of vRTIs by ages were 5.6 in infancy, 7.1 in preschool, and 4.0 in school children. The average number of cough and cold medications without other drugs prescribed per visit was two to three. Among cough and cold medications, antihistamines for systemic use were prescribed most frequently (20%), followed by mucolytics (12%), selective beta-2 agonists (11%), decongestants for systemic use (10%), and analgesic-antipyretics including acetaminophen (7%) or non-steroid anti-inflammatory drugs (6%). There was considerable variation of prescriptions, which increased with increasing age, where the top 20 prescription accounted for only 36%, 30%, and 25% of all prescriptions in infants, preschool, and school age children, respectively. CONCLUSIONS: A more rational use of medicines for treatment of vRTIs in children in Taiwan needs to be developed.

Utilization patterns of antihyperuricemic agents following safety announcement on allopurinol and benzbromarone by Taiwan Food and Drug Administration.

OBJECTIVE: The purpose of this study is to evaluate the utilization of four approved antihyperuricemic agents in Taiwan before and after two safety announcements rescinded an indication for allopurinol and added a warning on benzbromarone-induced hepatotoxicity in the year 2005. METHODS: An interrupted time series design and segmented regression models were used to examine impacts of the safety announcements on the utilization of allopurinol, benzbromarone, probenecid, or sulfinpyrazone. All outpatient prescriptions of the four antihyperuricemic agents were extracted from a longitudinal cohort dataset with 1000000 individuals randomly sampled from the National Health Insurance Research Database. We examined utilization patterns of antihyperuricemic agents before and after the policy intervention (i.e., safety announcements and labeling changes of allopurinol and benzbromarone) in the year 2005. RESULTS: Following the safety announcements, there was a reduction in the number of allopurinol users in the first year of intervention (-95.82 users per 100000 persons, 95%CI, [-166.84, -24.80]) and a continuous reduction afterward at a rate of -53.17 per 100000 persons per year. The utilization of benzbromarone grew steadily before 2005 but decreased drastically after the intervention, with a 30.12% reduction in the number of users by the end of year 2008. There was no commensurate change in the number of probenecid or sulfinpyrazone users after the intervention. CONCLUSIONS: Further research is required to evaluate the direct impacts of the safety announcements on clinical outcomes, treatment costs, and patient's quality of life.

Validation of acute myocardial infarction cases in the national health insurance research database in taiwan.

BACKGROUND: The aim of this study was to determine the validity of acute myocardial infarction (AMI) diagnosis coding in the National Health Insurance Research Database (NHIRD) by cross-comparisons of discharge diagnoses listed in the NHIRD with those in the medical records obtained from a medical center in Taiwan. METHODS: This was a cross-sectional study comparing records in the NHIRD and discharge notes in one medical center (DNMC) in the year 2008. Positive predictive values (PPVs) for AMI diagnoses were evaluated by reviewing the relevant clinical and laboratory data recorded in the discharge notes of the medical center. Agreement in comorbidities, cardiac procedures, and antiplatelet agent (aspirin or clopidogrel) prescriptions between the two databases was evaluated. RESULTS: We matched 341 cases of AMI hospitalizations from the two databases, and 338 cases underwent complete chart review. Of these 338 AMI cases, 297 were confirmed with clinical and lab data, which yielded a PPV of 0.88. The consistency rate for coronary intervention, stenting, and antiplatelet prescription at admission was high, yielding a PPV over 0.90. The percentage of consistency in comorbidity diagnoses was 95.9% (324/338) among matched AMI cases. CONCLUSIONS: The NHIRD appears to be a valid resource for population research in cardiovascular diseases.

Association Between Risk of Clostridium difficile Infection and Duration of Proton Pump Inhibitor or H2-Receptor Antagonist Use in Hospitalized Patients.

INTRODUCTION: Limited studies have evaluated the association between Clostridium difficile infection (CDI) and the duration of proton pump inhibitor (PPI) or histamine H2-receptor blocker (H2RA) use and provided a cutoff duration for PPI or H2RA use to mitigate a substantially increased risk of CDI. We aimed to evaluate these associations in hospitalized patients using a nationwide insurance claims database. METHODS: We conducted a nested case-control study to identify cases with a first ever record of CDI in a study cohort undergoing PPI or H2RA therapy from the National Health Insurance Database from 2012 to 2018. Each case was matched with one control by age, sex, and calendar year. We used conditional logistic regression to estimate the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC ROC). Youden's J statistic was used to identify the optimal cutoff duration in days for PPI or H2RA use. RESULTS: In the main analysis, the AUC ROC was 0.64 (95% CI 0.63-0.66) and optimal cutoff duration was 15 days for PPI users. The AUC ROC was 0.63 (95% CI 0.62-0.64) and optimal cutoff duration was 16 days for H2RA users. In the sensitivity analyses, the results were similar to those of the main analysis, and the optimal cutoff duration was in the range of 14-15 days. CONCLUSIONS: The optimal cutoff duration for PPI and H2RA use was about 2 weeks. It is necessary to be cautious regarding the risk of CDI in patients taking PPIs or H2RAs for longer than 2 weeks.

Beta-blockers reduce severe exacerbation in patients with mild chronic obstructive pulmonary disease with atrial fibrillation: a population-based cohort study.

BACKGROUND AND OBJECTIVE: Beta-blockers (BBs) decrease mortality and acute exacerbation (AE) rates in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular disease; however, information on their effects in patients with COPD and atrial fibrillation (AF) is limited. We aimed to assess the AE risk in patients with different severities of COPD and AF receiving BBs compared with that in patients receiving calcium channel blockers (CCBs). METHODS: This retrospective cohort study used data from the Taiwan National Health Insurance Database from 2009 to 2018. Outcomes included AE-related emergency room visits and hospitalisation. HRs and 95% CIs were estimated using the Cox proportional hazards model. COPD severity was classified as mild or severe based on exacerbation history. Sensitivity analyses included treatment and subgroup analyses, and competing risk adjustment. RESULTS: After propensity score matching, 4486 pairs of BB and CCB users from 13 462 eligible patients were included. The exacerbation risk for BB users was lower (HR 0.80; 95% CI 0.72 to 0.89) than that of CCB users. After stratification, BB benefits persisted in the mild COPD group (HR 0.75; 95% CI 0.66 to 0.85), unlike the severe COPD group (HR 0.95; 95% CI 0.75 to 1.20). The results of the subgroup analysis showed consistent protective effects even in patients without heart failure or myocardial infarction (adjusted HR 0.82; 95% CI 0.71 to 0.94). CONCLUSION: We found that BB use in patients with mild COPD and AF was associated with a lower exacerbation risk than CCB use, and that close monitoring of BB use in patients with severe COPD and AF is warranted.