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Background The assumptions of conventional spatial models cannot estimate the responses across space and over time. Spatial panel data models were proposed 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 set up 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. There was a higher proportion of high incidence rates in the western region than in the eastern region. The proportion of high incidence rates in the eastern areas increased over the years. It was found that most of “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. Conclusions Future comprehensive studies on townships located in higher-risk clusters of ESRD will help in setting up healthcare policies for suitable action.

Background The benefits of automated dispensing cabinets (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. Methods 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. A descriptive statistical analysis was performed to estimate the rates of medication errors before and after the adoption of ADCs, and Fisher’s exact test was to compare them. Results 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%. Conclusions 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.

Allopurinol‐related severe cutaneous adverse reactions (SCARs) are strongly associated with HLA‐B*58:01, the allele frequency (AF) of which is largely different among East Asians. However, evidence of population differences in SCAR development and relevance of genetic and/or other risk factors in the real‐world remain unelucidated. This study aimed to evaluate population differences in allopurinol‐related SCAR incidence related to genetic and/or other risk factors among East Asians in the real‐world. A population‐based cohort study was conducted using claims databases from Taiwan, Korea, and Japan. New users of allopurinol (311,846; 868,221; and 18,052 in Taiwan, Korea, and Japan, respectively) were followed up to 1 year. As control drugs, phenytoin and carbamazepine were used. The crude incidence rate ratios (IRRs) of SCARs for allopurinol against phenytoin or carbamazepine were the highest in Taiwan (IRR, 0.62 and 1.22; 95% confidence interval [CI], 0.54–0.72 and 1.01–1.47, respectively), followed by Korea (IRR, 0.34 and 0.82; 95% CI, 0.29–0.40 and 0.77–0.87), and the lowest in Japan (IRR, 0.04 and 0.16; 95% CI, 0.02–0.08 and 0.09–0.29). This order was accordant with that of AF ratios (AFRs) reported of HLA‐B*58:01 against alleles responsible for phenytoin‐ or carbamazepine‐related SCARs. The IRRs were higher in patients with chronic kidney disease, females, and elderly. This study demonstrated population differences in the risk of allopurinol‐related SCAR development among East Asians based on genetic and other common risk factors. This finding will help to promote appropriate risk management for allopurinol‐related SCARs based on ethnic origins. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THIS TOPIC? Allopurinol‐related severe cutaneous adverse reactions (SCARs) are strongly associated with HLA‐B*58:01, the allele frequency of which is largely different among East Asians. However, there is no direct real‐world evidence of population differences in SCAR development and the influence of genetic factors and/or other risk factors. WHAT QUESTION DID THIS STUDY ADDRESS? Do population differences in development of allopurinol‐related SCARs, depending on genetic factors and/or other risk factors, exist among three East Asians in the real‐world? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? The current analysis, based on comparisons of relative risks of SCAR incidence, provides real‐world evidence of population differences in allopurinol‐related SCAR development risk among East Asians, which was consistent with differences in reported HLA‐B*58:01 frequencies, as well as identifying chronic kidney disease, female gender, and old age as common risk factors. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? This study helps to promote appropriate risk management strategies for allopurinol‐related SCARs in the real‐world considering risk factors based on the patients’ ethnicity. Our approach is useful for evaluating population differences in the real‐world.

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.

Purpose Home-time has been found to correlate well with modified Rankin Scale (mRS) scores in patients with stroke. This study aimed to determine its correlations in patients with different types of stroke at various time points after stroke in a non-Western population. Methods This study used linked data from multi-center stroke registry databases and a nationwide claims database of health insurance. Functional outcomes as measured with the modified Rankin Scale were obtained from the registry databases and home-time was derived from the claims database. Spearman correlation coefficients were used to assess the correlation between home-time and mRS scores. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of home-time in predicting good functional outcome. Results This study included 7959 patients hospitalized for stroke or transient ischemic attack (TIA), for whom mRS scores were available in 6809, 6694, and 4330 patients at 90, 180, and 365 days, respectively. Home-time was highly correlated with mRS scores at the three time-points in patients with ischemic (Spearman's rho -0.69 to -0.83) or hemorrhagic (Spearman's rho -0.86 to -0.88) stroke, but the correlation was only weak to moderate in those with TIA (Spearman's rho -0.32 to -0.58). Home-time predicted good functional outcome with excellent discrimination in patients with ischemic (AUCs >0.8) or hemorrhagic (AUCs >0.9) stroke but less so in those with TIA (AUCs >0.7). Conclusion Home-time was highly correlated with mRS scores and showed excellent discrimination in predicting good functional outcome in patients with ischemic or hemorrhagic stroke. Home-time could serve as a valid surrogate measure for functional outcome after stroke.

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.

Background: \ud While there have been studies in adults reporting discordant empiric antibiotic treatment associated with poor outcomes, this area is relatively unexplored in children and neonates despite evidence of increasing resistance to recommended first-line treatment regimens.\ud \ud Methods: \ud Patient characteristics, antibiotic treatment, microbiology, and 30-day all-cause outcome from children

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.

When the human population is experiencing a decline but the turnover rate of pharmacists in general hospitals is gradually increasing, department of pharmacy starts to import more modern technologies including automation and artificial intelligence to aid in the workflow. One of the lengthy and routine work is to count the number of remaining medications of each ward, which requires many pharmacists and technicians depends on the size of hospital. This study thereby introduces a design of a medication assist device with an integration of the machine vision and multiple object recognition algorithm. The work can be divided into hardware design, data collection, training and validation, respectively. The recognition algorithm is based on deep learning Faster RCNN, which can successfully identify 7 classes of the anesthetics often used with an accuracy of 99.03%. This pilot study presents the capability of medication recognition, and the potential to expand numbers of medication.

Background: The pathophysiologic changes during critical illness and high minimal inhibitory concentration (MIC) pathogens are important risk factors of mortality and bacterial eradication in critical care. Beta-lactam antibiotics have a time-dependent effect on bactericidal activity. The continuous infusion (CIF) of beta-lactam antibiotics achieves sufficient drug concentration above the MIC, especially for critically ill patients. However, the superiority of CIF over intermittent infusion (IIF) of beta-lactam antibiotics is yet to be clearly established. Thus, we aimed to investigate the effects on mortality of CIF of beta-lactams antibiotics in comparison to those of IIF of beta-lactams antibiotics in patients with sepsis admitted to the intensive care unit (ICU).Methods: We systematically searched PUBMED, MEDLINE, Cochrane Library, EMBASE, Web of Science, and ICTRP for randomized controlled trials (RCTs) comparing CIF with IIF of beta-lactam antibiotics in critically ill populations. All RCTs published until October 2019 were eligible. The primary outcome measure was the relative risk (RR) of mortality, while the secondary outcome measures were bacterial eradication rate, length of ICU stay, and length of admission. Results: In total, 6 RCTs comprising 974 patients were analyzed. We found a significantly lower mortality for critically ill patients on CIF (RR: 0.79; 95% CI: 0.63, 0.98) compared with those on IIF of beta-lactam antibiotics. The pooled RR for the bacterial eradication rate was 1.16 (95% CI: 1.03, 1.29) for CIF compared with IIF administration. Conclusion: CIF of beta-lactam antibiotics for critically ill patients significantly reduces mortality and yields a better bacterial eradication rate than IIF. These findings support the clinical and bacterial eradication benefits in adult critically ill patients, and may guide clinical discussions and decisions.

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.

Purpose Home-time has been found to correlate well with modified Rankin Scale (mRS) scores in patients with stroke. This study aimed to determine its correlations in patients with different types of stroke at various time points after stroke in a non-Western population. Methods This study used linked data from multi-center stroke registry databases and a nationwide claims database of health insurance. Functional outcomes as measured with the modified Rankin Scale were obtained from the registry databases and home-time was derived from the claims database. Spearman correlation coefficients were used to assess the correlation between home-time and mRS scores. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of home-time in predicting good functional outcome. Results This study included 7959 patients hospitalized for stroke or transient ischemic attack (TIA), for whom mRS scores were available in 6809, 6694, and 4330 patients at 90, 180, and 365 days, respectively. Home-time was highly correlated with mRS scores at the three time-points in patients with ischemic (Spearman’s rho −0.69 to −0.83) or hemorrhagic (Spearman’s rho −0.86 to −0.88) stroke, but the correlation was only weak to moderate in those with TIA (Spearman’s rho −0.32 to −0.58). Home-time predicted good functional outcome with excellent discrimination in patients with ischemic (AUCs >0.8) or hemorrhagic (AUCs >0.9) stroke but less so in those with TIA (AUCs >0.7). Conclusion Home-time was highly correlated with mRS scores and showed excellent discrimination in predicting good functional outcome in patients with ischemic or hemorrhagic stroke. Home-time could serve as a valid surrogate measure for functional outcome after stroke.

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 Findings: 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. Haloperidol and risperidone exhibited a dose-response relationship with mortality risk after controlling for confounders. 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. The sensitivity analyses showed similar patterns. Interpretation: In post-stroke elderly patients, quetiapine would be favored over 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. Funding Statement: This research was supported in part by the Ministry of Science and Technology, Taiwan [grant number MOST 107-2320-B-006-035]. Declaration of Interests: The authors declare they have no conflict of interest with respect to this research study and paper. Ethics Approval Statement: The research protocol was approved by the Institutional Review Board of National Cheng Kung University Hospital (IRB No. A-EX-106-016).

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.

The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on overall community-acquired pneumonia (CAP) and disease severity still needs thorough evaluation. In this study, we retrieve both pneumococcal CAP (P-CAP) and unspecific CAP (U-CAP) inpatient data from the Taiwan National Health Insurance Database (NHID) between 2005 and 2016. The interrupted time-series (ITS) analysis was performed to compare the incidence trend before and after the implementation of PCV13. After PCV13 implementation, there is a significant decreasing trend of P-CAP hospitalization, especially in children &lt, 1 year, 2–5 years, adults aged 19–65 years, 66 years, or older (all p value &lt, 0.05). This corresponds to a 59% reduction in children &lt, 1 year, 47% in children aged 2–5 years, 39% in adult aged 19–65 years, and 41% in elderly aged 66 years or older. The intensive care rate (6.8% to 3.9%), severe pneumonia cases (21.7 to 14.5 episodes per 100,000 children–years), and the need for invasive procedures (4.3% to 2.0%) decreased in children aged 2–5 years (p value &lt, 0.0001) with P-CAP. This PCV13 implementation program in Taiwan not only reduced the incidence of P-CAP, but also attenuated disease severity, especially in children aged 2–5 years.

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.

Background: Aspirin is important and a valuable antiplatelet agent in clinical practice. Evaluating the risk of age-related macular degeneration (AMD) among long-term aspirin users compared with non-users is not fair due to confounding by indication. This study is aimed to estimate the risk of AMD among aspirin users compared with clopidogrel. Method: We conducted a population-based retrospective comparative cohort study using Taiwan's Longitudinal Health Insurance Database (LHID), which was randomly selected from the National Health Insurance Research Database (NHIRD). We included patients more than 45 years-old who initiated aspirin during 2001-2010 and they all tracked to 2013. The comparison groups are patients who were prescribed clopidogrel. The outcome of interest was AMD defined by ICD-9-CM code of 362·50-52 or 362·57. We used multivariate Cox regression modeling and propensity score matching to balance the characteristics of patients between groups to estimate the hazard ratio. Findings: After applying the methods, we had 109,534 aspirin users and 3,619 clopidogrel users. Male gender (51·12%) was predominate over females (48·88%) in the aspirin-user group. Our results showed no significant different risk of AMD between aspirin and clopidogrel users, while the multivariate Cox model showed HR was 1·13 (95% CI, 0·97 - 1·32) and the PS model showed HR was 1·09 (95% CI, 0·54-2·17). The incidence of aspirin users developing AMD was 8·18 per person-year, while the incidence of clopidogrel users was 10·07 per person-year. Interpretation: Patients with long-term use of aspirin did not have a higher risk of developing AMD compared to clopidogrel users. Funding: None. Declaration of Interest: All authors declare no conflict of interest. Ethical Approval: The study protocol was approved by the National Cheng Kung University Hospital Institutional Review Board (IRB) (NCKUH-IRB-A-EX-105-009).

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

Background Information on the incidence of venous thromboembolism (VTE) following hip fractures in Asia is rare. This study will investigate the epidemiology of symptomatic VTE in Taiwanese patients experiencing hip fractures. Methods and results We used Taiwan's National Health Insurance Research Database to retrospectively identify patients (≧ 45 years) who experienced hip fractures from 1998 to 2007 and were followed up for 3 months after the discharge. Logistic regression analysis determined the independent risk factors of symptomatic VTE after the fractures. We identified 134,034 patients (mean age: 76.2 ± 9.7 years; female: 57.8%) who experienced hip fractures, 83.2% of whom underwent hip surgery. The overall pharmacological thromboprophylaxis rate was 2.7%. The mean length of stay was 11.3 ± 7.9 days. The 3-month cumulative incidence of symptomatic VTE was 77 events per 10,000 persons. Multivariate analysis showed that previous DVT, previous PE, varicose veins, cancer, heart failure, renal insufficiency, and older age were independent risk factors of developing VTE. Conclusions The incidence of symptomatic VTE after hip fractures is low in Taiwan. Patients rarely received pharmacological thromboprophylaxis following hip fractures. Universal thromboprophylaxis for patients experiencing hip fractures was not necessary in Taiwan, but it should be considered in high-risk populations.

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.

Table S2. Incidence of diabetic retinopathy in eye examination groups compared with no eye examination groups among non-P4P population (check detection bias) (DOCX 15 kb)

Table S1. Baseline characteristics of the cohort patients with type 2 diabetes using propensity score (DOCX 16 kb)

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. Electronic supplementary material The online version of this article (10.1186/s12913-018-3454-6) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text, The CHADS2, CHA2DS2-VASc, and R2CHADS2 scores are well-known predictors of stroke caused by atrial fibrillation (AF), but no studies have evaluated their use for stratifying all-cause mortality risk in patients discharged for systolic heart failure (SHF) with or without AF. This study analyzed data in the Taiwan Society of Cardiology—heart failure with reduced ejection fraction (TSOC-HFrEF) registry. These data were obtained by a prospective, multicenter, observational survey of patients treated at 21 medical centers in Taiwan after hospitalization for acute, pre-existing or new onset SHF from May, 2013 to October, 2014. During 1 year follow-up, 198 patients were lost follow-up, and final 1311 (86.8%) patients were included for further analysis. During the follow-up period, 250 (19%) patients died. Multivariate analysis revealed that body mass index, thyroid disorder, valvular surgery history, chronic kidney disease (CKD), and scores for CHADS2, CHA2DS2-VASc, and R2CHADS2 were significant independent predictors of mortality in the overall population of SHF patients (all P

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. Copyright © 2015 John Wiley & Sons, Ltd.

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.

Background: The aim of this study was to determine the validity of acute myocardial infarction (AMI) diagnosiscoding in the National Health Insurance Research Database (NHIRD) by cross-comparisons of discharge diagnoseslisted 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 medicalcenter (DNMC) in the year 2008. Positive predictive values (PPVs) for AMI diagnoses were evaluated by reviewingthe relevant clinical and laboratory data recorded in the discharge notes of the medical center. Agreement incomorbidities, cardiac procedures, and antiplatelet agent (aspirin or clopidogrel) prescriptions between the twodatabases was evaluated.Results: We matched 341 cases of AMI hospitalizations from the two databases, and 338 cases underwent completechart review. Of these 338 AMI cases, 297 were confirmed with clinical and lab data, which yielded a PPVof 0.88.The consistency rate for coronary intervention, stenting, and antiplatelet prescription at admission was high, yieldinga PPVover 0.90. The percentage of consistency in comorbidity diagnoses was 95.9% (324/338) among matched AMIcases.Conclusions: The NHIRD appears to be a valid resource for population research in cardiovascular diseases.Key words: acute myocardial infarction; NHIRD; Taiwan; validity; pharmacoepidemiology

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 1 000 000 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 100 000 persons, 95%CI, [−166.84, −24.80]) and a continuous reduction afterward at a rate of −53.17 per 100 000 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. Copyright © 2013 John Wiley & Sons, Ltd.

Background Statin therapy has demonstrated benefits in ischemic stroke patients. However, little is known about whether the timing of statin initiation affects clinical outcomes. The possible association of statin use and cerebral hemorrhage is also a concern for early statin therapy after stroke. The objective of this study was to evaluate the efficacy and safety of the initiation timing of statins in acute ischemic stroke. Methods A cohort study was performed using 5-year National Health Insurance Research Database in Taiwan. Patients without prior statin therapy admitted for their new ischemic stroke or transient ischemic attack (TIA) were enrolled. Patients were recognized as inhospital use group (2019 patients, statin initiation during hospitalization), intermediate use group (2266 patients, statin initiation within 1 year after discharge) or late use group (2958 patients, statin initiation 1 year later after discharge). The study endpoint was the composite outcome of ischemic stroke, TIA, hemorrhagic stroke, or acute coronary event. Results As compared with inhospital use, patients with late use had a 49% increased risk (adjusted HR: 1.49, 95% CI: 1.26–1.76) of composite endpoint. In contrast, patients with intermediate use had similar risk of endpoint as those with inhospital use. The risk of cerebral hemorrhage was similar in patients receiving inhospital, intermediate, or late statin treatment. Conclusions In acute ischemic stroke, patients receiving late statin treatment carried a poorer clinical outcome than those with earlier statin initiation. Inhospital statin use after an acute ischemic stroke did not increase the risk of cerebral hemorrhage.

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. Copyright © 2013 John Wiley & Sons, Ltd. Language: en

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.

Background: The epidemiology of symptomatic venous thromboembolism (VTE) in Taiwan has not been well investigated. The aim of this study was to report on the epidemiology and short-term prognosis of symptomatic VTE. Methods and Results: This nationwide population-based cohort study used the Taiwanese National Health Insurance claims databases to identify adults older than 18 years of age with symptomatic VTE diagnosed in 2002. We investigated the clinical features of VTE and determined independent risk factors of 1-month mortality. A total of 2,774 patients were identified with a mean age of 62.8 years and the female-to-male ratio was 1.15:1. The crude incidence of symptomatic VTE was 16.5 per 100,000 persons, which steadily increased with age, ranging from 4 per 100,000 in patients

Objective The National Health Insurance Research Database (NHIRD) is commonly used for pharmacoepidemiological research in Taiwan. This study evaluated the validity of the database for patients with a principal diagnosis of ischemic stroke. Study design and methods This cross-sectional study compares records in the NHIRD with those in one medical center. Patients hospitalized for ischemic stroke in 1999 were identified from both databases. The discharge notes, laboratory data, and medication orders during admission and the first discharge visit were reviewed to validate ischemic stroke diagnoses and aspirin prescribing in the NHIRD. Agreement between the two databases in comorbidities of ischemic stroke diagnosis was evaluated using ICD-9 codes. Results Three hundred and seventy two cases were identified from the NHIRD; among them, 364 cases (97.85%) were confirmed as ischemic stroke by radiology examination and clinical presentation. Among these confirmed cases, 344 (94.51%) were assigned ‘ischemic stroke’ as the principal diagnosis in the NHIRD. The overall agreement of comorbid diagnoses between the databases was 48.39%. The PPV for selected conditions also varied widely, from 0.50 for fracture to 1.00 for colon cancer. The accuracy of recorded aspirin prescriptions was higher in first post-discharge visits (PPV = 0.94) than during hospitalization (PPV = 0.88). Conclusion The accuracy of the NHIRD in recording ischemic stroke diagnoses and aspirin prescriptions was high, and the NHIRD appears to be a valid resource for population research in ischemic stroke. Copyright © 2010 John Wiley & Sons, Ltd.

Summary. Background: Little information is available on the epidemiology of venous thromboembolism (VTE) in Asian populations. Objectives: To investigate VTE incidence, VTE cumulative recurrence rates and risk factors for VTE recurrence among the adult Taiwanese population. Methods: This population-based cohort study used the Taiwanese National Health Insurance claims databases to identify 5347 adult patients (2463 men, 46.1%) with VTE diagnosed in 2001 and 2002. We calculated the crude incidence of VTE and its recurrence. We also conducted a nested case–control study (n = 3576) among this population to estimate the association between VTE recurrence and exposure to potential VTE risk factors by conditional logistic regression. Results: The crude incidence of VTE was 15.9 per 100 000 person-years, and its recurrence rate was 5.1% per person-year. During 11 566 person-years of follow-up, the cumulative rates of VTE recurrence at 6, 12, 24, 36 and 47 months were 6.7%, 9.4%, 12.4%, 13.9%, and 14.4%, respectively. By conditional logistic regression, histories of VTE [adjusted odds ratio (OR) 1.71, 95% confidence interval (CI) 1.32–2.16] or malignant neoplasm (adjusted OR 1.64, 95% CI 1.26–1.99), major extremity trauma (adjusted OR 2.76, 95% CI 1.82–4.52), serious neurologic diseases (adjusted OR 1.43, 95% CI 1.12–1.84) or undergoing major surgery (adjusted OR 4.57, 95% CI 1.72–12.50) were associated with higher risks of VTE recurrence. Conclusions: The incidence of VTE is lower in the Taiwanese population than in Caucasians. Most VTE recurrences occur within 12 months, but they continue to occur beyond 1 year. The VTE recurrences are associated with malignancy, history of VTE, and major surgery after a previous VTE.

C. -H . LEE ,*† T . -C . L IN ,† C. L . CHENG,† C. -Y . YANG,‡ L . J . L IN*† and Y . -H . KAO YANG†§ *Department of Internal Medicine, National Cheng Kung University Hospital; †Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University; ‡Department of Orthopedics, National Cheng Kung University Hospital; and §Health Outcome Research Center, National Cheng Kung University, Tainan, Taiwan

Purpose Incorrect dosage was the most common type of medication errors in neonate patients. Different dosing recommendations from common reference sources may have contributed to the errors. This study assesses the compliance rate with the common reference sources in antibiotic dosage prescribed for preterm infants in a neonatal intensive care unit (NICU). Methods A retrospective study using chart review was conducted at a tertiary care medical center with university affiliation in Taiwan. Study subjects were preterm neonates admitted to the NICU of the medical center between 2000 and 2002 and prescribed at least one antibiotic during the stay. Recommendations from three commonly used reference sources (Pediatric Dosage Handbook, Neonatal Drug Formulary, and Neofax) were employed to evaluate the dosage compliance of the antibiotic prescriptions. Results A total of 433 preterm infants and 3459 prescriptions were included. Depending on the reference source used, the percentages of antibiotic prescriptions where both the dose and the interval were compliant with recommendations ranged from 36.88 to 87.54%. Conclusions A significant proportion of antibiotics prescribed for preterm neonates in this medical center did not comply with the recommended dosage from common reference sources. Future studies should investigate the clinical impacts of the dosing deviation. Copyright © 2009 John Wiley & Sons, Ltd.