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.

Suboptimal Outcomes and Retreatment Rate of Patients With Crohn's Disease After Forced Discontinuation of Biologics: A Nationwide Population-Based Study.

Taiwan's National Health Insurance (NHI) program forced discontinuation of biologic use in Crohn's disease (CD) after a limited treatment duration, regardless of disease activity. This study investigated the retreatment rate and suboptimal outcomes (i.e., CD-related surgeries, hospitalizations, emergency room visits, and oral steroid flare-ups) after forced discontinuation. This retrospective cohort study was conducted using data from the NHI Database. Patients who received ≥40 weeks of biologic treatment followed by a forced discontinuation were included. The time of biologic retreatment and the cumulative incidence of suboptimal outcomes after the forced discontinuation as well as related risk factors were analyzed. Included were 215 patients (68% male). At the beginning of biologic therapy, the mean age (±SD) was 35.7 (±13.5) years, and the disease duration was 4.46 (±3.52) years. The median (interquartile range) biologic treatment duration was 57.86 (50.3-83.3) weeks. Within the first year after forced discontinuation, 67% of patients (n = 144) were retreated with a second course of biologics, and 53% of patients (n = 114) experienced at least one suboptimal outcome. The independent risk factors associated with the occurrence of suboptimal outcomes were CD-related emergency room visits and hospitalizations during biologic therapy (hazard ratio: 2.49; 95% confidence interval: 1.59-3.89). More than two-thirds of patients with CD required biological retreatment within 1 year after a forced discontinuation. The substantial proportion of patients with poor disease outcomes highlights the need to continue the biologic.

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.

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.

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.

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 Effectiveness of Bevacizumab versus Cetuximab in Metastatic Colorectal Cancer Patients without Primary Tumor Resection.

Primary tumor resection may be unfeasible in metastatic colorectal cancer. We determined the effects of bevacizumab and cetuximab therapies on survival or conversion surgery in patients with metastatic colorectal cancer who did not undergo primary tumor resection. This retrospective cohort study enrolled 8466 patients who underwent first-line bevacizumab- or cetuximab-based therapy. We analyzed the data of both therapies in patients who did not undergo primary tumor resection. Overall survival after targeted therapy plus chemotherapy was assessed. The groups were matched using propensity score matching and weighting. Cetuximab resulted in lower mortality than bevacizumab (hazard ratio (HR) = 0.75); however, it did not have the same effect in patients that underwent primary tumor resection (HR = 0.95) after propensity score weighting. Among patients treated with targeted agents, primary tumor resection was associated with lower mortality among those who received both bevacizumab (HR = 0.60) and cetuximab (HR = 0.75). Among patients that did not undergo primary tumor resection, multivariable analysis for conversion surgery showed that the cetuximab group (HR = 1.82) had a significantly higher metastasectomy rate. In these patients, cetuximab-based therapy was associated with significantly better survival compared with bevacizumab-based therapy. Cetuximab also yielded a higher conversion surgery rate. These findings demonstrate the importance of stratification by primary tumor resection in the application of current treatment guidelines and initiation of future clinical trials.

Decrease of Pneumococcal Community-Acquired Pneumonia Hospitalization and Associated Complications in Children after the Implementation of the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) in Taiwan.

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 <1 year, 2-5 years, adults aged 19-65 years, 66 years, or older (all p value < 0.05). This corresponds to a 59% reduction in children <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 < 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.

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.

Association of Empiric Antibiotic Regimen Discordance With 30-Day Mortality in Neonatal and Pediatric Bloodstream Infection-A Global Retrospective Cohort Study.

BACKGROUND: 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. METHODS: Patient characteristics, antibiotic treatment, microbiology, and 30-day all-cause outcome from children <18 years with blood-culture-confirmed bacterial bloodstream infections (BSI) were collected anonymously using REDCap™ through the Global Antibiotic Prescribing and Resistance in Neonates and Children network from February 2016 to February 2017. Concordance of early empiric antibiotic treatment was determined using European Committee on Antimicrobial Susceptibility Testing interpretive guidelines. The relationship between concordance of empiric regimen and 30-day mortality was investigated using multivariable regression. RESULTS: Four hundred fifty-two children with blood-culture-positive BSI receiving early empiric antibiotics were reported by 25 hospitals in 19 countries. Sixty percent (273/452) were under the age of 2 years. S. aureus, E. coli, and Klebsiella spp. were the most common isolates, and there were 158 unique empiric regimens prescribed. Fifteen percent (69/452) of patients received a discordant regimen, and 7.7% (35/452) died. Six percent (23/383) of patients with concordant regimen died compared with 17.4% (12/69) of patients with discordant regimen. Adjusting for age, sex, presence of comorbidity, unit type, hospital-acquired infections, and Gram stain, the odds of 30-day mortality were 2.9 (95% confidence interval: 1.2-7.0; P = 0.015) for patients receiving discordant early empiric antibiotics. CONCLUSIONS: Odds of mortality in confirmed pediatric BSI are nearly 3-fold higher for patients receiving a discordant early empiric antibiotic regimen. The impact of improved concordance of early empiric treatment on mortality, particularly in critically ill patients, needs further evaluation.

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.

Real-world evidence of population differences in allopurinol-related severe cutaneous adverse reactions in East Asians: A population-based cohort study.

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.

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.

Home-Time as a Surrogate Measure for Functional Outcome After Stroke: A Validation Study.

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.

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.

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.

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.