Exposure-Response to High PM 2.5 Levels for Cardiovascular Events in High-risk Older Adults in Taiwan.

Background: Multiple studies from countries with relatively lower PM 2.5 level demonstrated that acute and chronic exposure even at lower than recommended level, e.g., 9 µg/m 3 in the US increased the risk of cardiovascular (CV) events. However, limited studies using individual level data exist from countries with a wider range of PM levels to illustrate shape of the exposure-response curve throughout the range including > 20 µg/m 3 PM 2·5 concentrations. Taiwan with its policies reduced PM 2.5 over time provide opportunities to illustrate the dose response curves and how reductions of PM 2.5 over time correlated with CV events incidence in a nationwide sample. Methods: Using data from the 2009-2019 Taiwan National Health Insurance Database linked to nationwide PM2.5 data. We examined the shape and magnitude of the exposure-response curve between seasonal average PM 2·5 level and CV events-related hospitalizations among older adults at high-risk for CV events. We used history-adjusted marginal structural models including potential confounding by individual demographic factors, baseline comorbidities, and health service measures. To quantify the risk below and above 20 µg/m 3 we conducted stratified Cox regression. We also plotted PM 2.5 and CV events from 2009-2019 as well as average temperature as a comparison. Findings: Using the PM 2.5 concentration <15 µg/m 3 (Taiwan regulatory standard) as a reference, the seasonal average PM 2.5 concentration (15-23.5µg/m 3 and > 23.5 µg/m 3 ) were associated with hazard ration of 1.13 (95%CI 1.09-1.18) and 1.19 (95%CI 1.14-1.24), 1.07 (95%CI 1.03-1.11) and 1.14 (95%CI 1.10-1.18), 1.22 (95%CI 1.08-1.38) and 1.31 (95%CI 1.16-1.48), 1.04 (95%CI 0.98-1.10) and 1.10 (95%CI 1.04-1.16) respectively for HF, IS/TIA,PE/DVT and MI/ACS. A nonlinear relationship between PM 2·5 and CV events outcomes was observed at PM 2·5 levels above 20 µg/m 3 . Interpretation: A nonlinear exposure-response relationship between PM2·5 concentration and the incidence of cardiovascular events exists when PM2.5 is higher than the levels recommended by WHO Air Quality Guidelines. Further lowering PM2·5 levels beyond current regulatory standards may effectively reduce the incidence of cardiovascular events, particularly HF and DVT, and can lead to tangible health benefits in high-risk elderly population.

Assessing the effectiveness of targeted agents in adjuvant therapy for patients with metastatic colorectal cancer undergoing surgical resection: a retrospective cohort study.

Background: Primary tumor resection and metastasectomy may be beneficial for many patients with metastatic colorectal cancer (mCRC). Objective: To assess the differences in postoperative survival outcomes between adjuvant therapy with chemotherapy alone and chemotherapy plus targeted agents (TAs). Design: Retrospective cohort study. Methods: Patients with mCRC who underwent surgical resection for primary colorectal tumor and distant metastases and received adjuvant therapy from 1 January 2010 to 31 December 2017 were enrolled in the Taiwan Cancer Registry. We analyzed the overall survival of patients with resectable or initially unresectable mCRC who received adjuvant chemotherapy alone and chemotherapy plus TAs. Results: We enrolled 1124 and 542 patients with resectable and initially unresectable mCRC, respectively. Adjuvant chemotherapy plus TAs and chemotherapy alone resulted in similar mortality rates among patients with resectable mCRC [adjusted hazard ratio (aHR) = 1.13; 95% confidence interval (CI), 0.93-1.36]; however, it marginally reduced the mortality rate among patients with initially unresectable mCRC who underwent conversion surgery after neoadjuvant therapy (aHR = 0.81; 95% CI, 0.62-1.06). The subgroup analysis of patients who received more than nine cycles of TAs preoperatively and anti-epidermal growth factor receptor agents revealed aHRs of 0.48 (95% CI, 0.27-0.87) and 0.33 (95% CI, 0.18-0.60), respectively. Conclusion: Adjuvant chemotherapy plus TAs may improve survival in patients with initially unresectable tumors who underwent conversion surgery following neoadjuvant therapy with TAs, especially in those who respond well to the targeted therapy. Our study underscores the importance of stratifying patients with mCRC based on tumor resectability when selecting the adjuvant therapy regimen.

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.

Ambient Heat and Risk of Serious Hypoglycemia in Older Adults With Diabetes Using Insulin in the U.S. and Taiwan: A Cross-National Case-Crossover Study.

OBJECTIVE: To measure the association between ambient heat and hypoglycemia-related emergency department visit or hospitalization in insulin users. RESEARCH DESIGN AND METHODS: We identified cases of serious hypoglycemia among adults using insulin aged ≥65 in the U.S. (via Medicare Part A/B/D-eligible beneficiaries) and Taiwan (via National Health Insurance Database) from June to September, 2016-2019. We then estimated odds of hypoglycemia by heat index (HI) percentile categories using conditional logistic regression with a time-stratified case-crossover design. RESULTS: Among ∼2 million insulin users in the U.S. (32,461 hypoglycemia case subjects), odds ratios of hypoglycemia for HI >99th, 95-98th, 85-94th, and 75-84th percentiles compared with the 25-74th percentile were 1.38 (95% CI, 1.28-1.48), 1.14 (1.08-1.20), 1.12 (1.08-1.17), and 1.09 (1.04-1.13) respectively. Overall patterns of associations were similar for insulin users in the Taiwan sample (∼283,000 insulin users, 10,162 hypoglycemia case subjects). CONCLUSIONS: In two national samples of older insulin users, higher ambient temperature was associated with increased hypoglycemia risk.

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.

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.

Risk of Incident Epilepsy After a Middle Cerebral Artery Territory Infarction.

Background: Among poststroke morbidities, poststroke epilepsy (PSE) has been identified as a significant clinical issue. Although middle cerebral artery (MCA) infarct is the most common type of stroke among all vascular territories, very few studies specifically focused on the risk factors leading to PSE in patients with MCA infarct. Methods: A population study in Taiwan has been conducted, linking the National Health Insurance Research Database and Hospital Stroke Registry, from 2001 to 2015 and 2006 to 2010, respectively. Patients were divided into MCA and non-MCA groups, and the diagnosis of incident epilepsy between the groups has been compared. The multivariable Cox proportional hazard model was used to identify the risk factors for developing PSE. The distribution of time to PSE was estimated using the Kaplan-Meier method. Results: In total, 1,838 patients were recruited, with 774 and 1,064 in the MCA and non-MCA groups, respectively. PSE incidence in the MCA group was 15.5% vs. 6.2% in the non-MCA group, with a hazard ratio of (95% CI) 2.06 (1.33-3.19). Factors significantly associated with PSE included atrial fibrillation, depression, National Institutes of Health Stroke Scale (NIHSS) scores of ≥ 16, and alert on arrival. For patients with MCA infarct, higher NIHSS and Glasgow coma scale scores, the presence of visual field defects and weakness, urination control impairment, and complications during hospitalization were associated with a higher risk for PSE development. Conclusions: This study established the conditions leading to a higher risk of PSE and identified the important clinical risk factors in patients experiencing MCA infarct. Efforts to manage these risk factors may be important in preventing PSE in patients with MCA infarct.

Metabolic events associated with the use of antipsychotics in children, adolescents and young adults: a multinational sequence symmetry study.

It is known that younger patients treated with antipsychotics are at increased risk of metabolic events; however, it is unknown how this risk varies according to ethnicity, the class of antipsychotic and the specific product used, and by age group. We conducted a multinational sequence symmetry study in Asian populations (Hong Kong, Japan, Korea, Taiwan and Thailand) and non-Asian populations (Australia and Denmark) to evaluate the metabolic events associated with antipsychotics in both Asian and non-Asian populations, for typical and atypical antipsychotics, and by the subgroups of children and adolescents, and young adults. Patients aged 6-30 years newly initiating oral antipsychotic drugs were included. We defined a composite outcome for metabolic events which included dyslipidemia, hypertension and hyperglycemia. We calculated the sequence ratio (SR) by dividing the number of people for whom a medicine for one of the outcome events was initiated within a 12-month period after antipsychotic initiation by the number before antipsychotic initiation. This study included 346,904 antipsychotic initiators across seven countries. Antipsychotic use was associated with an increased risk of composite metabolic events with a pooled adjusted SR (ASR) of 1.22 (95% CI 1.00-1.50). Pooled ASRs were similar between Asian (ASR, 1.22; 95% CI 0.88-1.70) and non-Asian populations (ASR, 1.22; 95% CI 1.04-1.43). The pooled ASR for typical and atypical antipsychotics was 0.98 (95% CI 0.85-1.12) and 1.24 (95% CI 0.97-1.59), respectively. No difference was observed in the relative effect in children and adolescents compared to young adults. The risk of metabolic events associated with antipsychotics use was similar in magnitude in Asian and non-Asian populations despite the marked difference in drug utilization patterns.

Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.

AIMS: The risk of antipsychotic-associated cardiovascular and metabolic events may differ among countries, and limited real-world evidence has been available comparing the corresponding risks among children and young adults. We, therefore, evaluated the risks of cardiovascular and metabolic events in children and young adults receiving antipsychotics. METHODS: We conducted a multinational self-controlled case series (SCCS) study and included patients aged 6-30 years old who had both exposure to antipsychotics and study outcomes from four nationwide databases of Taiwan (2004-2012), Korea (2010-2016), Hong Kong (2001-2014) and the UK (1997-2016) that covers a total of approximately 100 million individuals. We investigated three antipsychotics exposure windows (i.e., 90 days pre-exposure, 1-30 days, 30-90 days and 90 + days of exposure). The outcomes were cardiovascular events (stroke, ischaemic heart disease and acute myocardial infarction), or metabolic events (hypertension, type 2 diabetes mellitus and dyslipidaemia). RESULTS: We included a total of 48 515 individuals in the SCCS analysis. We found an increased risk of metabolic events only in the risk window with more than 90-day exposure, with a pooled IRR of 1.29 (95% CI 1.20-1.38). The pooled IRR was 0.98 (0.90-1.06) for 1-30 days and 0.88 (0.76-1.02) for 31-90 days. We found no association in any exposure window for cardiovascular events. The pooled IRR was 1.86 (0.74-4.64) for 1-30 days, 1.35 (0.74-2.47) for 31-90 days and 1.29 (0.98-1.70) for 90 + days. CONCLUSIONS: Long-term exposure to antipsychotics was associated with an increased risk of metabolic events but did not trigger cardiovascular events in children and young adults.

Trends in coagulation factor replacement therapy and medical costs in patients with haemophilia in Taiwan: A population-based, 15-year analysis.

INTRODUCTION: Taiwan's National Health Insurance Program approved reimbursement of prophylactic coagulation factor replacement therapy (CFRT) for patients with haemophilia (PWH) in 2014. AIM: To examine 15-year trends and the impact of reimbursement for prophylactic CFRT on its utilization and related medical costs for PWH. METHODS: We analysed Taiwan's National Health Insurance Database from 2003 to 2017. We included patients with haemophilia A (PWHA) or B (PWHB) receiving coagulating factor. Female patients were excluded because of small sample size. We analysed annual consumption of CFRT units and medical costs. High proportion of days covered (PDC) with CFRT served as an indicator for prophylactic treatment since it reflects routine use of CFRT. We applied interrupted time series analysis (ITSA) to evaluate the impact of reimbursement for prophylactic CFRT on usage patterns and medical costs. RESULTS: We included 896 male PWHA and 181 male PWHB, with 38.1% and 37.0% aged under 18 years, respectively. By ITSA, we found the trends in coagulation factor consumption and PDC significantly increased after reimbursement for prophylactic CFRT in both PWHA and PWHB (p values for trend change <0.05). The overall medical costs per patient increased with increasing consumption of coagulation factor; however, ITSA revealed non-CFRT cost decreased after reimbursement of prophylactic CFRT for both PWHA and PWHB (p values <.05). CONCLUSION: Reimbursement for prophylactic CFRT facilitated growth in rates of prophylactic CFRT and increased related costs, but curbed rising non-CFRT costs. These findings provide strong grounds for future cost-effectiveness studies to leverage prophylactic CFRT for its therapeutic benefits.

Comparative cardiometabolic risk of antipsychotics in children, adolescents and young adults.

Understanding different cardiometabolic safety profiles of antipsychotics helps avoid unintended outcomes among young patients. We conducted a population-based study to compare cardiometabolic risk among different antipsychotics in children, adolescents and young adults. From Taiwan's National Health Insurance Database, 2001-2013, we identified two patient cohorts aged 5-18 (children and adolescents) and 19-30 (young adults), diagnosed with psychiatric disorders and newly receiving antipsychotics, including haloperidol and sulpiride, and second generation antipsychotics (SGA, including olanzapine, quetiapine, risperidone, amisulpride, aripiprazole, paliperidone, and ziprasidone). Risperidone users were considered the reference group. We analyzed electronic medical records from seven hospitals in Taiwan and confirmed findings with validation analyses of identical design. Primary outcomes were composite cardiometabolic events, including type 2 diabetes mellitus, hypertension, dyslipidemia, and major adverse cardiovascular events. Multivariable Cox proportional hazards regression models compared cardiometabolic risk among antipsychotics. Among 29,030 patients aged 5-18 and 50,359 patients aged 19-30 years, we found 1200 cardiometabolic event cases during the total follow-up time of 37,420 person-years with an incidence of 32.1 per 1000 person-years. Compared to risperidone, olanzapine was associated with a significantly higher risk of cardiometabolic events in young adults (adjusted hazard ratio, 1.57; 95% CIs 1.13-2.18) but not in children and adolescents (1.85; 0.79-4.32). Specifically, we found young adult patients receiving haloperidol (1.52; 1.06-2.20) or olanzapine (1.75; 1.18-2.61) had higher risk of hypertension compared with risperidone users. Results from validation analyses concurred with main analyses. Antipsychotics' various risk profiles for cardiometabolic events merit consideration when selecting appropriate regimes. Due to cardiometabolic risk, we suggest clinicians may consider to select alternative antipsychotics to olanzapine in children, adolescents and young adults.

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.

Incidence, prevalence and prescription patterns of antipsychotic medications use in Asia and US: A cross-nation comparison with common data model.

The use of antipsychotic medications (APMs) could be different among countries due to availability, approved indications, characteristics and clinical practice. However, there is limited literature providing comparisons of APMs use among countries. To examine trends in antipsychotic prescribing in Taiwan, Hong Kong, Japan, and the United States, we conducted a cross-national study from 2002 to 2014 b y using the distributed network approach with common data model. We included all patients who had at least a record of antipsychotic prescription in this study, and defined patients without previous exposure of antipsychotics for 6 months before the index date as new users for incidence estimation. We calculated the incidence, prevalence, and prescription rate of each medication by calendar year. Among older patients, sulpiride was the most incident [incidence rate (IR) 11.0-23.3) and prevalent [prevalence rate (PR) 11.9-14.3) APM in Taiwan, and most prevalent (PR 2.5-3.9) in Japan. Quetiapine and haloperidol were most common in the United States (IR 8.1-9.5; PR 18.0-18.4) and Hong Kong (PR 8.8-13.7; PR 10.6-12.7), respectively. The trend of quetiapine use was increasing in Taiwan, Hong Kong and the United States. As compared to older patients, the younger patients had more propensity to be prescribed second-generation APM for treatment in four countries. Trends in antipsychotic prescribing varied among countries. Quetiapine use was most prevalent in the United States and increasing in Taiwan and Hong Kong. The increasing use of quetiapine in the elderly patients might be due to its safety profile compared to other APMs.

The use of activated vitamin D and risks of hospitalization for infection and amputation in incident hemodialysis patients in Taiwan: a nationwide population-based cohort study.

BACKGROUND: Hemodialysis patients have a high risk of mortality. The most common causes of death are cardiovascular disease and infection. The potential hazard or benefit associated with vitamin D use and cardiovascular or infection outcome is poorly characterized. METHODS: We conducted a retrospective observational cohort study by recruiting 52,757 patients older than 20 years from Taiwan National Health Insurance Research Database (NHIRD) who initiated maintenance hemodialysis between 2001 and 2009. Patients who were prescribed activated vitamin D before the 360th day from hemodialysis initiation were defined as vitamin D users. The primary outcome of interest includes occurrence of acute myocardial infarction (AMI), ischemic stroke, lower limb amputation, and hospitalization for infection, respectively, while death events are treated as competing events. We conducted competing risk analysis using subdistribution hazard regression model to estimate subdistribution hazard ratios (SHRs) in relation to various outcomes. RESULTS: During the median follow-up of 1019 days, the vitamin D users had a lower crude mortality rate, lower incidences of AMI, ischemic stroke, amputation, and hospitalization for infection compared with non-users. Taking into consideration competing events of death, vitamin D users were associated with a lower hazard of lower limb amputation (SHR 0.84 [95% CI, 0.74-0.96]) and hospitalization for infection (SHR 0.90 [95% CI, 0.87-0.94]), but not AMI or ischemic stroke, after adjustment for potential confounders. Subgroup analyses and dose response evaluation both showed a consistent association of activated vitamin D treatment with decreased risk of amputation and infection. CONCLUSION: The findings suggest that therapeutic activated vitamin D use in hemodialysis patients may be beneficial for decreasing infection events and amputation, of which the latter is a complication of peripheral vascular disease, rather than reducing major atherosclerotic cardiovascular events such as AMI or ischemic stroke.

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.

Workload of pharmacists and the performance of pharmacy services.

OBJECTIVE: To evaluate the influence of pharmacists' dispensing workload (PDW) on pharmacy services as measured by prescription suggestion rate (PSR) and dispensing error rate (DER). METHOD: This was an observational study in northern and southern Taiwan's two largest medical centers, from 2012 to 2018. We calculated monthly PDW as number of prescriptions divided by number of pharmacist working days. We used monthly PSR and DER as outcome indicators for pharmacists' review and dispensing services, respectively. We used Poisson regression model with generalized estimation equation methods to evaluate the influence of PDW on PSR and DER. RESULTS: The monthly mean of 463,587 (SD 32,898) prescriptions yielded mean PDW, PSR and DER of 52 (SD 3) prescriptions per pharmacist working days, 30 (SD 7) and 8 (SD 2) per 10,000 prescriptions monthly, respectively. There was significant negative impact of PDW on PSR (adjusted rate ratio, aRR: 0.9786; 95%CI: 0.9744-0.9829) and DER (aRR: 0.9567; 95%CI: 0.9477-0.9658). Stratified analyses by time periods (2012-2015 and 2016-2018) revealed the impact of PDW on PSR to be similar in both periods; but with positive association between PDW and DER in the more recent one (aRR: 1.0086, 95%CI: 1.0003-1.0169). CONCLUSIONS: Reduced pharmacist workload was associated with re-allocation of pharmacy time to provide prescription suggestions and, more recently, decrease dispensing errors. Continuous efforts to maintain appropriate workload for pharmacists are recommended to ensure prescription quality.

Aromatase Inhibitors and Risk of Arthritis and Carpal Tunnel Syndrome among Taiwanese Women with Breast Cancer: A Nationwide Claims Data Analysis.

Tamoxifen or aromatase inhibitor (AI) therapy may prevent breast cancer recurrence, however, adverse effects may lead to treatment discontinuation. Evidence regarding the occurrence of AI-associated musculoskeletal problems among Asians is scarce. We identified women with breast cancer-initiating tamoxifen or AIs from the Taiwan National Health Insurance Research Database (2007-2012). Using multivariable cause-specific hazard models, we examined the association between endocrine therapy and the risk of any arthritis and carpal tunnel syndrome, adjusting for age, prior cancer treatment, and other health status factors. Among 32,055 eligible women with breast cancer (mean age = 52.6 ± 11.5 years), 87.4% initiated tamoxifen, 3.9% initiated anastrozole, 8.0% initiated letrozole, and 0.7% initiated exemestane. AI users had a higher 1-year cumulative incidence for any arthritis (13.0% vs. 8.2%, p < 0.0001) and carpal tunnel syndrome (1.4% vs. 0.8%, p = 0.008). Compared to tamoxifen users, AI users had a higher risk of any arthritis [adjusted hazard ratio (aHR) = 1.21, 95%CI = 1.09-1.34] and carpal tunnel syndrome (aHR = 1.68, 95%CI = 1.22-2.32). No significant difference was observed in the risks of any arthritis and carpal tunnel syndrome across different AIs. Taxane use was not associated with any arthritis (aHR = 0.92, 95%CI = 0.81-1.05) or carpal tunnel syndrome (aHR = 0.97, 95%CI = 0.67-1.40) compared to other chemotherapies. Taiwanese women with breast cancer-initiating AIs had an increased risk of arthritis and carpal tunnel syndrome compared to those who initiated tamoxifen.

Favorable pleiotropic effects of sodium glucose cotransporter 2 inhibitors: head-to-head comparisons with dipeptidyl peptidase-4 inhibitors in type 2 diabetes patients.

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors have shown greater reductions of cardiovascular event risks than dipeptidyl peptidase-4 (DPP4) inhibitors, whereby possible mechanisms may involve the better pleiotropic effects of SGLT2 inhibitors. However, no published data are currently available to directly compare glycemic and pleiotropic effects in real-world type 2 diabetes patients initiating SGLT2 inhibitors or DPP4 inhibitors. METHOD: We conducted a retrospective cohort study by analyzing the Chang Gung Research Database, the largest multi-institutional electronic medical records database in Taiwan. We included patients newly receiving SGLT2 inhibitor or DPP4 inhibitor intensification therapy for type 2 diabetes from 2016 to 2017. We matched SGLT2 inhibitor users to DPP4 inhibitor users (1:4) by propensity scores to ensure comparable characteristics between the groups. We primarily evaluated 1-year post-treatment changes of hemoglobin A1c (HbA1c) after SGLT2 inhibitor or DPP4 inhibitor initiation, using two-tailed independent t-test. We also evaluated post-treatment changes in body weight, systolic blood pressure (SBP), alanine aminotransferase (ALT) and estimated glomerular filtration rate (eGFR) values, associated with SGLT2 inhibitors and DPP4 inhibitors. RESULTS: We identified a cohort of 2028 SGLT2 inhibitors and 8112 matched DPP4 inhibitors new users. SGLT2 inhibitors and DPP4 inhibitors showed similar HbA1c reductions (- 1.0 vs. - 1.1%; P = 0.076), but patients receiving SGLT2 inhibitors had greater improvements in body weight (- 1.5 vs. - 1.0 kg; P = 0.008), SBP (- 2.5 vs. - 0.7 mmHg; P < 0.001) and ALT values (- 4.1 vs. - 0.0 U/l; P < 0.001) and smaller declines in eGFR values (- 2.0 vs. - 3.5 ml/min/1.73 m2; P < 0.001) when compared to DPP4 inhibitors. CONCLUSION: SGLT2 inhibitors had glucose-lowering effects comparable to those of DPP4 inhibitors but more favorable pleiotropic effects on body weight, ALT and eGFR changes, potentially improving type 2 diabetes patients' cardio-metabolic disease risks.

Effects of sodium-glucose co-transporter-2 inhibitors on serum alanine aminotransferase levels in people with type 2 diabetes: A multi-institutional cohort study.

Clinical trials have indicated that sodium-glucose co-transporter-2 (SGLT2) inhibitors have a favourable effect on serum alanine aminotransferase (ALT) levels in people with type 2 diabetes (T2D), but supporting evidence from real-world studies is lacking. We identified patients with T2D who initiated SGLT2 inhibitors during the period 2016 to 2017 from Chang Gung Research Database, which covers 1.3 million individuals from seven hospitals (6% of the Taiwan population). We classified patients by baseline ALT level and evaluated changes in ALT values from baseline to 1 year after initiation of SGLT2 inhibitors. We identified 11 690 new users of SGLT2 inhibitors with a mean (SD) age of 59.3 (11.8) years. The mean (SD) glycated haemoglobin and ALT levels were 8.9 (1.7)% and 34.7 (28.9) U/L at baseline, respectively. The mean change in ALT levels was -5.0 U/L (95% confidence interval [CI] -6.4, -3.5) 1 year after initiation of SGLT2 inhibitors. In patients with ALT levels ≤1× the upper limit of normal (ULN), the change in ALT levels was 1.6 U/L (95% CI -0.1, 3.4), while in those with ALT levels >1× ULN, the change in ALT levels was -26.5 U/L (95% CI -28.6, -24.3). The higher the baseline ALT level, the greater the decline after SGLT2 inhibitor treatment. Our findings suggest the initiation of SGLT2 inhibitors for T2D management could improve serum ALT levels in clinical practice, particularly in patients with especially high ALT levels.

Comparative risk evaluation for cardiovascular events associated with dapagliflozin vs. empagliflozin in real-world type 2 diabetes patients: a multi-institutional cohort study.

BACKGROUND: To compare the cardiovascular event risk in type 2 diabetes patients newly receiving dapagliflozin vs. empagliflozin. METHODS: We conducted a retrospective cohort study by analyzing a multi-institutional electronic medical records database (Chang Gung Research Database) in Taiwan and included adult type 2 diabetes patients who were newly receiving sodium-glucose co-transporter 2 (SGLT2) inhibitors from 2016 to 2017. The primary outcome was a composite of cardiovascular death, myocardial infarction, ischemic stroke and heart failure. We followed up patients from initiation of SGLT2 inhibitors until the occurrence of cardiovascular events before December 31, 2018. We performed multivariable Cox proportional hazard modeling, adjusting for patients' age, sex, laboratory data, co-morbidities, and concomitant medications. RESULTS: We identified 12,681 new SGLT2 inhibitor users with a mean age of 58.9 (SD 11.8) years, of whom 43.9% were female and 45.8% were new dapagliflozin users. A total of 10,442 person-years of dapagliflozin use and 12,096 person-years of empagliflozin use were included. Compared to empagliflozin users, new users of dapagliflozin were found to have similar risks for primary composite outcome (adjusted HR: 0.91; 95% CI 0.73-1.14), cardiovascular death (adjusted HR: 0.54; 95% CI 0.14-2.12), myocardial infarction (adjusted HR: 0.77, 95% CI 0.49-1.19) and ischemic stroke (adjusted HR: 1.15; 95% CI 0.80-1.65), but a lower risk of heart failure (adjusted HR: 0.68; 95% CI 0.49-0.95). CONCLUSION: The risk of cardiovascular events was similar between dapagliflozin and empagliflozin new users, but dapagliflozin may have a better outcome in the reduction of heart failure in type 2 diabetes patients. Future prospective studies are required to confirm the findings.