Longitudinal evaluation of adverse events due to steroid use in primary immune thrombocytopenia: A population-based study.

This study aimed to investigate the association between the steroid use patterns and the risk of AEs in patients with primary immune thrombocytopenia (ITP). A total of 2691 newly diagnosed adults with ITP between 2011 and 2018 were identified from the National Health Insurance Research Database in Taiwan, and the date of first steroid use was defined as the index date. Post-index steroid use was calculated on a 90-day basis as a time-dependent variable and categorized by the average prednisolone-equivalent daily dose (<10 mg vs. ≥10 mg) and intensity (medication possession ratio <80% vs. ≥80%). Patients were followed up for 1 year from the index date for acute AE events, while chronic AEs were assessed until death, or end of 2019. Compared to patients with low-dose+low-intensity steroid use, those with high-dose+high-intensity steroid use were associated with a higher risk of acute AE (adjusted incident rate ratio [aIRR]: 1.57, 95% confidence interval [CI]: 1.38-1.78, p < 0.01) and chronic AE (aIRR: 1.26, 95% CI: 1.08-1.47, p < 0.01). Metabolic/endocrine and ophthalmologic disorders demonstrated the strongest correlation with a high dose and intensity. The joint effect of steroid dose and intensity was observed in patients with ITP, and the findings suggest that steroids should be used carefully.

Comparison of endoscopic third ventriculostomy versus cerebrospinal fluid shunt procedures for the treatment of pediatric hydrocephalus in Taiwan.

PURPOSE: Pediatric hydrocephalus is the most common cause of surgically treatable neurological disease in children. Controversies exist whether endoscopic third ventriculostomy (ETV) or cerebrospinal fluid (CSF) shunt placement is the most appropriate treatment for pediatric hydrocephalus. This study aimed to compare the risk of re-operation and death between the two procedures. METHODS: We performed a retrospective population-based cohort study and included patients younger than 20-years-old who underwent CSF shunt or ETV for hydrocephalus from the Taiwan National Health Insurance Research Database. RESULTS: A total of 3,555 pediatric patients from 2004 to 2017 were selected, including 2,340 (65.8%) patients that received CSF shunt placement and 1215 (34.2%) patients that underwent ETV. The incidence of all-cause death was 3.31 per 100 person-year for CSF shunt group and 2.52 per 100 person-year for ETV group, with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI] = 0.66-0.94, p = 0.009). The cumulative incidence competing risk for reoperation was 31.2% for the CSF shunt group and 26.4% for the ETV group, with an adjusted subdistribution HR of 0.82 (95% CI = 0.70-0.96, p = 0.015). Subgroup analysis showed that ETV was beneficial for hydrocephalus coexisting with brain or spinal tumor, central nervous system infection, and intracranial hemorrhage. CONCLUSION: Our data indicates ETV is a better operative procedure for pediatric hydrocephalus when advanced surgical techniques and instruments are available.

Mortality in anorexia nervosa and bulimia nervosa: A population-based cohort study in Taiwan, 2002-2017.

OBJECTIVE: To investigate natural- and unnatural-cause mortality at different follow-up time points in Taiwanese patients with anorexia nervosa (AN) and bulimia nervosa (BN). METHOD: In this longitudinal cohort study, 330,393 patients, including 2143 patients with AN, 13,590 with BN, and 20 times as many respective non-AN and non-BN patients, were followed up for 16 years. We performed conditional Cox regression survival analysis to examine the risk of mortality in the AN and BN groups relative to the comparison group. RESULTS: A total of 1242 patients died, including 101 and 343 patients with AN and BN, respectively. Mortality rates for AN and BN were 5.42 and 2.90 deaths per 1000 person-years, respectively. Compared with the non-AN group, the AN group had a significantly higher risk of both natural- and unnatural-cause mortality, and the BN group had a significantly higher risk of unnatural-cause mortality. Suicide was the most common cause of death, and suicide risk was significantly higher in both the AN and BN groups. All-cause mortality risk was the highest at the beginning of follow-up and markedly declined in the AN group. In the BN group, all-cause mortality risk was lower but stable at follow-up. The risk of unnatural-cause mortality remained high throughout the follow-up period for both the groups. CONCLUSIONS: Early detection and treatment for associated physical problems in patients with AN are crucial. Regular monitoring for unnatural-cause mortality events (mainly suicide) in AN and BN over time is also crucial. PUBLIC SIGNIFICANCE: AN had a significantly higher risk of both natural- and unnatural-cause mortality and BN had a significantly higher risk of death from unnatural causes. All-cause mortality risk was highest at the beginning of follow-up in AN, but unnatural-cause mortality risk remained high throughout the follow-up period for both groups. Our findings imply that early detection and treatment in AN and regular monitoring for unnatural-cause mortality events in AN and BN are crucial.

Risk of dialysis and renal diseases in patients with anorexia nervosa in Taiwan.

OBJECTIVE: To investigate the incidence and risk of renal-related complications in a nationwide cohort of Taiwanese patients with anorexia nervosa (AN). METHOD: This longitudinal cohort study analyzed the data of 43,951 individuals-comprising 2091 patients with AN and their controls matched (1:20) using propensity scores according to sex, age, degree of urbanization of residence, socioeconomic status, and year of diagnosis-from a population-based health insurance database; the study lasted 16 years. We used Kaplan-Meier curves to estimate the cumulative incidence of renal events. We also performed Cox proportional regression and constructed a risk model with death as a competing event (both adjusted for basic characteristics, renal diseases, and psychiatric comorbidities) to examine the risk of dialysis and renal outcomes in the AN group relative to the control group. RESULTS: In total, 204 and 10 patients with AN had renal-related outcomes and end-stage renal disease (ESRD), respectively. The cumulative incidence rates of all renal outcomes and ESRD in the AN group were 10.72% and .64%, respectively, at 10-year follow-up. Compared with the control group, the AN group had a significantly higher risk of acute dialysis (adjusted hazard ratio 2.10 [95% confidence interval 1.19-3.68]), hypokalemia, hypovolemia, nephritis, acute renal failure, and chronic renal failure. The AN group did not have a significantly higher risk of ESRD. DISCUSSION: The elevated risks of acute dialysis and some renal outcomes in AN highlight the importance of monitoring electrolyte imbalance and renal malfunctioning. PUBLIC SIGNIFICANCE: Malnutrition and purging behaviors may cause renal complications in patients with AN. In this longitudinal cohort study, we found that the 10-year cumulative incidence of all renal outcomes in AN was 10.72%, and that patients with AN had a two-fold higher risk of overall renal outcomes compared with those without AN. Our findings imply that weight restoration and ceasing purging behaviors are crucial for recovery from AN.

Metformin Adherence Reduces the Risk of Dementia in Patients With Diabetes: A Population-based Cohort Study.

OBJECTIVE: Metformin is widely used as the first-line drug for type 2 diabetes mellitus and has numerous benefits apart from lowering blood glucose. However, metformin-retained regimen is challenged by newly launching, powerful glucose-lowering antiglycemic agents. This population-based cohort study examined the association between metformin adherence and the risk of dementia and Parkinson's disease (PD). METHODS: Diabetic patients with metformin-included combination antiglycemic therapy were identified from the National Health Insurance Research Database and categorized into metformin-adherent and -nonadherent groups according to the medical record of the first year prescription. Patients contraindicated with metformin, severe diabetic complications, and poor drug compliance were excluded. The study outcome was the diagnosis of dementia or PD. RESULTS: A total of 31 384 matched pairs were included after using propensity score matching and both groups were followed up for an average of 5 years. Metformin adherence was associated with a significantly lower risk of dementia (adjusted hazard risk ratio = 0.72, P < .001) but not PD (adjusted hazard risk ratio = 0.97, P = .825). Subgroup analysis revealed that the risk of dementia was significantly reduced in metformin-adherent patients, both male and female, aged >65 or ≤ 65 years, and with or without concurrent insulin treatment. This effect was not influenced by concurrent insulin treatment, which may eliminate the bias caused by the severity of diabetes mellitus. CONCLUSION: Despite the launching of numerous new oral antiglycemic agents, metformin may provide further benefit on lowering risk of dementia beyond conventional glycemic control according to the real-world evidence.

Triple therapy for Helicobacter pylori eradication and the risk of hypoglycemia in patients with diabetes: a population-based cohort study.

The incidence of type 2 diabetes mellitus has risen globally, from 108 million cases in 1980 to 422 million cases in 2014. Although controlling glycemic levels in patients with diabetes is crucial, insulin and sulfonylureas can cause hypoglycemic episodes and even potentially fatal events such as comas, seizures, life-threatening arrhythmias, and myocardial infarctions. Several antibiotics have been documented to cause hypoglycemic episodes; the use of antibiotics along with insulin or sulfonylureas might further increase the risk of hypoglycemia. Therefore, researchers must determine which antibiotics carry a risk of inducing severe hypoglycemic events. The prevalence of H. pylori infection remains high in most countries, and the infection is often treated with triple therapy involving amoxicillin, clarithromycin, and a proton pump inhibitor (PPI). Several case reports have reported that hypoglycemia can occur when used with patients who also take diabetes medication. Therefore, we hypothesized that patients with diabetes have an increased risk of hypoglycemic episodes when being treated with triple therapy for H. pylori infection. By analyzing medical records from Taiwan's National Health Insurance Research Database, we found a significant association between hypoglycemia and triple therapy treatment for diabetic patients with peptic ulcer disease. Prescribing triple therapy to patients with diabetes and peptic ulcers significantly increased the risk of a hypoglycemic episode (adjusted odds ratio [aOR] = 1.75, 95% confidence interval [CI]: 1.64 to 1.88, P < 0.001). Similarly, the highest aOR (5.77, 95% CI 4.82 to 6.92) was found in patients with diabetes and peptic ulcers who had hypoglycemic episodes within 30 days after triple therapy treatment. Many patients with diabetes require H.pylori eradication for peptic ulcer treatment, and vigilance toward the risk of hypoglycemia in this population is thus necessary.

Epidemiology and survival outcomes of acute myeloid leukemia patients in Taiwan: A national population-based analysis from 2001 to 2015.

OBJECTIVES/BACKGROUND: Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with high mortality. To date, there is no comprehensive population-based analysis of patients with AML in Asia, including Taiwan. MATERIAL AND METHODS: This is a retrospective cohort study using three population-based databases, namely, the Taiwan Cancer Registry, Taiwanese National Health Insurance Research Database, and Taiwan Death Registry, between 2001 and 2015 to provide detailed information on patients with AML and relevant clinical variables, such as sex, age, year of diagnosis, socioeconomic status (SES) level, hospital level, treatment location, and Deyo-Charlson Comorbidity Index (Deyo-CCI) score. RESULTS: Patients with newly diagnosed AML (n = 9949) were included in the study. The median age was 60 years, and the overall age-adjusted AML incidence over 15 years was 2.44 per 100,000 person-years. The median overall survival (OS) of patients younger than 65 years was 18 months, whereas the OS of patients older than age 65 was only 5 months. AML patients with a prior cancer history had the worst outcomes, and the acute promyelocytic leukemia subtype predicted better survival. Patients who were older, male and a higher Deyo-CCI score had a significantly higher risk of death. In contrast, patients with a higher SES level and receiving treatment in a medical center had a lower risk of mortality than their respective counterparts. CONCLUSION: Our study results could enable clinicians to obtain a comprehensive picture of the epidemiology, survival outcomes and unmet medical needs of AML patients in Taiwan.

Effectiveness of induction regimens on survival outcome in acute myeloid leukemia patients: a real-world data from 2001 to 2015.

Since patients with acute myeloid leukemia (AML) in the real world have a much different clinical picture than patients recruited in the clinical trials, obtaining real-world evidence of medication adoption is important for therapeutic efficiency and safety. This study used three population-based data in Taiwan, the National Health Insurance Research Database, Taiwan Cancer Registry, and National Death Registry, between 2001 and 2015, to investigate the effect of conventional chemotherapy (CCT) versus non-conventional chemotherapy (NCCT) on the overall survival (OS) of patients with AML (n = 7,763). Cox proportional hazard regression was used to estimate the hazard ratios (HR) of different treatments on the risk of mortality. To reduce the potential selection bias, we used the inverse probability of treatment weighting based on the propensity score to balance the baseline characteristics between patients receiving CCT and NCCT. The median survival time for CCT and NCCT arms was 10.2 months (95% confidence interval (95% CI): 9.7-10.9) and 4.1 months (95% CI: 3.8-4.5), respectively. Compared to the patients received NCCT, those receiving CCT had a lower risk of mortality (HR 0.63 (95% CI: 0.59-0.67, P < 0.001). Subgroup analysis showed that CCT did benefit patients in different gender, age, comorbidity, and socioeconomic status (SES) groups. In conclusion, the real-world population-based data exhibited CCT were more likely to be prescribed for patients with AML of younger age, fewer comorbidities, diagnosed recently (2011-2015), and higher SES. In fact, CCT had better treatment outcomes than NCCT in terms of OS for adult patients diagnosed with AML.

Prescription patterns and dosages of antiepileptic drugs in prevalent patients with epilepsy in Taiwan: A nationwide retrospective cross-sectional study.

OBJECTIVE: To evaluate the prescription patterns and prescribed daily dose (PDD)/defined daily dose (DDD) ratios of antiepileptic drugs (AEDs) in prevalent patients with epilepsy in Taiwan. MATERIALS AND METHODS: A nationwide retrospective cross-sectional study was conducted for prevalent patients with epilepsy in 2016 using the Taiwanese National Health Insurance Research Database. The prescription records of AEDs of all prevalent patients with epilepsy were retrieved. The mean PDDs and PDD/DDD ratios of AEDs in adult patients were obtained to evaluate dosing adequacy. A chi-square test and two-sample t test were used to analyze the differences in AED prescription patterns and dosages, respectively, among patients with different ages, sexes, comorbidities, and therapeutic approaches. RESULTS: A total of 118,937 prevalent patients with epilepsy were enrolled. The predominant therapeutic approach was monotherapy, especially in the elder adults, accounting for 82.9% of elder adult patients with epilepsy. The proportion of AED monotherapy was higher in patients with dementia (78.9%) and stroke (80.6%). The top three antiepileptic monotherapies were valproic acid (28.7%), levetiracetam (19.1%), and phenytoin (16.9%); however, oxcarbazepine (22.8%) was substituted for carbamazepine (3.9%) as monotherapy for patients aged 0-17 years. Among adult patients with epilepsy, the PDD/DDD ratio of each AED in monotherapy was less than 1.00. The mean PDD of each AED was higher in polytherapy than in monotherapy (p < 0.01), except for lacosamide. The mean PDDs of all evaluated AEDs in monotherapy were lower in elder adult patients than in younger adult patients, most of which reached statistical significance (p < 0.001). CONCLUSIONS: In Taiwan, valproic acid was the most prescribed AED for prevalent patients with epilepsy. The mean PDDs of most AEDs were lower than the DDDs developed by the World Health Organization.

Timing of symptomatic subsequent vertebral compression fracture associated with different demographic factors.

BACKGROUND: Symptomatic subsequent vertebral compression fracture (VCF; SVCF) is a common complication associated with poor outcomes. Accumulating evidence shows that demographic factors and incidences of symptomatic SVCFs differ during different periods after the primary vertebroplasty (VP). PURPOSE: To investigate the incidence and demographic factors of symptomatic SVCFs after the primary VP in different periods using registry data in the Taiwan National Health Insurance Research Database. METHODS: This retrospective cohort study included 28,343 patients aged ≥ 50 years with painful VCF treated with VP from 2002 to 2016. Symptomatic SVCF was defined as SVCF requiring another VP or re-admission. During the 2-year follow-up, 1955 patients received subsequent VP while 1,407 were readmitted. Cox proportional hazard models were used to compare the risks of subsequent VP or readmission. RESULTS: The cumulative incident rate of subsequent VP and re-hospitalization was 0.87 [95% confidence interval (CI), 0.82 ~ 0.92] and 0.62 (95% CI, 0.58 ~ 0.66) per 100 person-months, respectively, within the first 6 months after the primary VP, and it decreased over time. A multiple Cox regression model showed that age, osteopenia or osteoporosis, Charlson comorbidity index (CCI) were significant independent risk factors of subsequent VP or readmission within the first 6 months. CONCLUSIONS: This study demonstrated that the incidence of symptomatic SVCF peaked in the first 6 months after the primary VP. Age, osteoporosis or osteopenia, and CCI were determined to be risk factors in the first 6 months, but only osteoporosis or osteopenia and CCI were risk factors thereafter.

Real-world cost-effectiveness analysis of the fracture liaison services model of care for hip fracture in Taiwan.

BACKGROUND: This study was to perform an economic evaluation to understand clinical outcomes and health resource use between hip fracture patients receiving hospital-based postfracture fracture liaison service (FLS) care and those receiving usual care (UC) in Taiwan. METHODS: This cohort study included hospital-based data of 174 hip fracture patients who received FLS care (FLS group) from National Taiwan University Hospital, and 1697 propensity score-matched patients who received UC (UC group) of National Health Insurance claim-based data. Two groups had similar baseline characteristics but differed in hip fracture care after propensity score matching. Clinical outcomes included refracture-free survival (RFS), hip-refracture-free survival (HRFS), and overall survival (OS). Health resource use included inpatient, outpatient, and pharmacy costs within 2 years follow-up after the index of hip fracture. The economic evaluation of the FLS model was analyzed using the net monetary benefit regression framework based on the National Health Insurance perspective. RESULTS: The FLS group had longer RFS than the UC group, with an adjusted difference of 44.3 days (95% confidence interval: 7.2-81.4 days). Two groups did not differ in inpatient and outpatient costs during follow-up, but the FLS group had a higher expenditure than the UC group on osteoporosis-related medication. The probability of FLS being cost-effective was >80% and of increasing RFS, HRFS, and OS was 95%, 81%, and 80%, respectively, when the willingness-to-pay threshold was >USD 65/gross domestic product per day. CONCLUSION: FLS care was cost-effective in reducing refracture occurrence days for patients initially diagnosed with hip fractures.

Cardiogenic shock in Taiwan from 2003 to 2017 (CSiT-15 study).

BACKGROUND: This study investigated temporal trends in the treatment and mortality of patients with cardiogenic shock (CS) in Taiwan in relation to acute myocardial infarction (AMI) accreditation implemented in 2009 and the unavailability of percutaneous ventricular assist devices. METHODS: Data of patients diagnosed as having CS between January 2003 and December 2017 were collected from Taiwan's National Health Insurance Research Database. Each case was followed from the date of emergency department arrival or hospital admission for the first incident associated with a CS diagnosis up to a 1-year interval. Measurements included demographics, comorbidities, treatment, mortality, and medical costs. Using an interrupted time-series (ITS) design with multi-level mixed-effects logistic regression model, we assessed the impact of AMI accreditation implementation on the mortality of patients with AMI and CS overall and stratified by the hospital levels. RESULTS: In total, 64 049 patients with CS (mean age:70 years; 62% men) were identified. The incidence rate per 105 person-years increased from 17 in 2003 to 25 in 2010 and plateaued thereafter. Average inpatient costs increased from 159 125 points in 2003 to 240 993 points in 2017, indicating a 1.5-fold increase. The intra-aortic balloon pump application rate was approximately 22-25% after 2010 (p = 0.093). Overall, in-hospital, 30-day, and 1-year mortality declined from 60.3%, 63.0%, and 69.3% in 2003 to 47.9%, 50.8% and 59.8% in 2017, respectively. The decline in mortality was more apparent in patients with AMI-CS than in patients with non-AMI-CS. The ITS estimation revealed a 2% lower in-hospital mortality in patients with AMI-CS treated in district hospitals after the AMI accreditation had been implemented for 2 years. CONCLUSIONS: In Taiwan, the burden of CS has consistently increased due to high patient complexity, advanced therapies, and stable incidence. Mortality declined over time, particularly in patients with AMI-CS, which may be attributable to advancements in AMI therapies and this quality-improving policy.

Long-term exposure to ozone and sulfur dioxide increases the incidence of type 2 diabetes mellitus among aged 30 to 50 adult population.

AIMS/HYPOTHESIS: Worldwide, the information regarding the associations between long-term exposure to ozone (O3) and sulfur dioxide (SO2) and the development of type 2 diabetes remains scarce, especially in Asia. This study aimed to investigate the long-term effects of exposure to ambient O3 and SO2 on the incidence of type 2 diabetes with consideration of other air pollutants in Taiwanese adults aged 30 to 50 years. METHODS: A total of 6,426,802 non-diabetic participants aged between 30 and 50 years old were obtained from the National Health Insurance Research Database between 2005 and 2016. Incident type 2 diabetes was the main diagnosis at medical visits. Air quality data were provided by the Taiwan Environmental Protection Administration. The air pollutant concentrations for each participant were estimated using the ordinary kriging method to interpolate daily concentrations of O3, SO2, carbon monoxide (CO), nitrogen dioxide (NO2), suspended fine particles (with an aerodynamic diameter less than 2.5 µm; PM2.5), and suspended particles (with an aerodynamic diameter less than 10 µm; PM10) in residential districts across Taiwan. Six-year average concentrations of pollutants were calculated from January 1, 2005 to December 31, 2010, and data were categorized into quartiles. We performed Cox regression models to analyze the long-term effects of exposure to O3 and SO2 on the incidence of type 2 diabetes. RESULTS: The hazard ratio (HR) for the incidence of diabetes per each interquartile range (IQR) increase in ozone exposure (3.30 ppb) was 1.058 (95% confidence interval (CI): 1.053, 1.064) and 1.011 (95% CI: 1.007, 1.015) for SO2 exposure (1.77 ppb) after adjusting for age, sex, socioeconomic status, urbanization level, temperature, humidity, and chronic comorbidities (Model 3). Furthermore, for every 3.30 ppb increase of O3, the HR for incident type 2 diabetes was 1.093 (95% CI: 1.087, 1.100) after controlling factors shown in Model 3 plus SO2 and PM2.5. On the other hand, for every 1.77 ppb increase of SO2, the HR for incident type 2 diabetes was 1.073 (95% CI: 1.068, 1.079) after controlling factors shown in Model 3 plus NO2 and PM2.5. CONCLUSIONS: Long-term exposure to ambient O3 and SO2 was associated with a higher risk of developing type 2 diabetes for Taiwanese population. Exposure to O3 and SO2 may play a role in the adult early-onset type 2 diabetes.

Combination therapies with thiazolidinediones are associated with a lower risk of acute exacerbations in new-onset COPD patients with advanced diabetic mellitus: a cohort-based case-control study.

BACKGROUND: The effects of oral antihyperglycaemic drugs (OADs) for type 2 diabetes mellitus (T2DM) on the outcomes of co-existing chronic obstructive pulmonary disease (COPD) patients are not well studied. We examined the association of combinational OADs and the risk of acute exacerbations of COPD (AECOPD) in T2DM patients with co-existing COPD. METHODS: A cohort-based case-control study was conducted using data from the National Health Insurance Research Database of Taiwan. Among new-onset COPD-T2DM patients, 65,370 were prescribed metformin and 2nd-line OADs before the date of COPD onset. Each AECOPD case was matched to 4 randomly selected controls according to the propensity score estimated by the patient's baseline characteristics. Conditional logistic regression analysis was performed to estimate the association between AECOPD risk and OAD use. RESULTS: Among COPD-T2DM patients, 3355 AECOPD cases and 13,420 matched controls were selected. Of the patients treated with a double combination of oral OADs (n = 12,916), those treated with sulfonylurea (SU) and thiazolidinediones (TZD) had a lower AECOPD risk than the patients who received metformin (MET) and SU, with an adjusted odds ratio (OR) of 0.69 (95% confidence interval [CI] 0.51-0.94, P = 0.02). Of the patients with a triple combination of oral OADs (n = 3859), we found that those treated with MET, SU and TZD had a lower risk of AECOPD (adjusted OR 0.81 (0.68-0.96, P = 0.01) than a combination of MET, SU and α-glucosidase inhibitors (AGIs) regardless of the level of COPD complexity. CONCLUSION: Combination therapies with TZD were associated with a reduced risk of AECOPD in advanced T2DM patients with co-existing COPD.

Comparing the effectiveness of different EGFR-TKIs in patients with EGFR mutant non-small-cell lung cancer: A retrospective cohort study in Taiwan.

The study was to compare the effectiveness of different epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced non-small-cell lung cancer (NSCLC) and received EGFR-TKIs as first-line therapy. This retrospective cohort study was conducted using data from real-world settings. Patients with stage IIIB and IV NSCLC and first received gefitinib, erlotinib, or afatinib between 2011 and 2015 were included. The date of the first claim for EGFR-TKIs was set as the index date. Study endpoints were all-cause death and treatment failure that was defined when patients added on or switched to chemotherapy or terminal care. A total of 5,940 patients, including 3,982 (67.0%) receiving gefitinib, 1,207 (20.3%) receiving erlotinib, and 751 (12.7%) receiving afatinib, were eligible for this study. The 1-year overall survival (OS) rates for gefitinib, erlotinib, and afatinib groups were 74% (95% confidence interval [CI]: 72-75%), 75% (95% CI: 73-77%), and 80% (95% CI: 77-83%), respectively. Compared to gefitinib, afatinib was associated with a lower risk of all-cause death (adjusted hazard ratio [aHR] = 0.82, 95% CI: 0.72-0.93) but not erlotinib (aHR = 0.95, 95% CI: 0.86-1.05). Similar results were also found regarding the effectiveness of treatment. All the three EGFR-TKIs showed no differences for both outcomes among patients with an Eastern Cooperative Oncology Group Performance Score of 2. The real-world data exhibited afatinib was more likely to be used for younger patients in a better condition than other EGFR inhibitors, and observed prolonged OS and treatment effectiveness compared to gefitinib after performing a multivariate Cox regression analysis.

Percutaneous coronary intervention in patients hospitalized for non-ST-elevation myocardial infarction and the risk of postdischarge ischemic stroke at 6-month, 1-year, and 3-year follow-ups.

Percutaneous coronary intervention (PCI) is suggested for treating patients with non-ST-elevation myocardial infarction (NSTEMI) to reduce adverse cardiovascular events. However, the short- and long-term effects of PCI on the risk of postdischarge ischemic stroke (IS) in patients hospitalized for NSTEMI remain unclear. This study investigated the association of PCI on the risk of postdischarge IS in patients hospitalized for NSTEMI at different period follow-ups. A population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database. Propensity score matching (PSM) was used to select 6079 pairs of the patients with NSTEMI treated invasively by PCI (received PCI during hospitalization) and initial conservative strategy (did not receive PCI during hospitalization) with similar baseline characteristics for evaluation. After adjustment for patients' clinical variables and the duration of dual antiplatelet therapy, PCI was associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups [adjusted hazard ratio (aHR) = 0.41, 95% confidence interval (CI) = 0.26-0.67, p < 0.001; aHR = 0.61, 95% CI 0.43-0.86, p = 0.004; and aHR = 0.69, 95% CI 0.54-0.89, p = 0.005respectively]. In the patients who had a CHA2DS2-VASc score of ≥2, PCI was also associated with a decreased risk of postdischarge IS at 6-month, 1-year, and 3-year follow-ups (aHR = 0.54, 95% CI 0.36-0.83, p = 0.005; aHR = 0.72, 95% CI 0.52-1.00, p = 0.048; and aHR =0.73, 95% CI 0.58-0.91, p = 0.005, respectively). These findings suggested that PCI might reduce the risk of postdischarge IS in patients hospitalized for NSTEMI.

Productivity growth and quality changes of hospitals in Taiwan: does ownership matter?

As the competition in the Taiwanese medical industry becomes increasingly fierce, public hospitals are confronted with challenges in orientation and operations. This study measured changes in the operational efficiency of public and their competitors, non-public hospitals, in Taiwan. This study considered differences in technology and scale between public and non-public hospitals and adopted the quality-incorporating metafrontier Malmquist productivity index to analyze inputs, outputs, and quality achievements of hospitals. The data consisted of 40 public hospitals and 79 non-public hospitals in Taiwan during the period 2008-2014. This study measured productivity growth and quality changes. Moreover, it further identified technological gaps and quality gaps in different types of hospitals with respect to the metafrontier. At the same time, comparisons of changes in quality between public and non-public hospitals were also examined. The empirical results showed that public hospitals were better than non-public ones in terms of productivity. Meanwhile, it was also found that most of the decomposition in productivity was higher in public hospitals than in non-public ones, especially in terms of improvements in technology and quality. This paper presented public hospitals outperformed non-public ones during the research period in spite of the fact that private hospitals had become larger and group-oriented. Therefore, public hospitals and regulators made appropriate adjustments and responses in the face of the pressure of competition in the market.

Health Care Costs and Utilization of Dabigatran Compared With Warfarin for Secondary Stroke Prevention in Patients With Nonvalvular Atrial Fibrillation: A Retrospective Population Study.

BACKGROUND: It remains unclear whether the use of new oral anticoagulants, compared with warfarin, is economically beneficial in Asian countries. OBJECTIVE: The objective of this study is to compare the health care costs and utilization between dabigatran and warfarin in a real-world nonvalvular atrial fibrillation (NVAF) population. RESEARCH DESIGN: Data were obtained from the Taiwan National Health Insurance Database, and patients with an NVAF diagnosis between June 1, 2012, and May 31, 2014, were identified using the International Classification of Diseases, Ninth Revision code of 427.31. The patients in the dabigatran cohort were matched 1:2 to those in the warfarin cohort by sex, age, residential region, and a propensity score that incorporated a major bleeding history, CHADS2 score, and Charlson Comorbidity Index. The all-cause health care utilization and associated costs of the 2 treatment groups were compared at 3 and 12 months. RESULTS: A total of 1149 patients taking dabigatran were identified and matched with 2298 warfarin users. During the 3-month observation period, the likelihood of having at least 1 hospitalization among dabigatran users was significantly lower than that of warfarin users (odds ratio=0.78; P=0.001). Patients in the dabigatran group incurred lower mean emergency department costs ($2383.1 vs. $3033.6), mean ischemic stroke-related hospitalization costs ($8869.5 vs. $13,990.5), and mean all-cause hospitalization costs ($32,402.2 vs. $50,669.9) at 3 months. However, both the mean and median outpatient costs of warfarin users were consistently lower than those of dabigatran users ($17,161.2 vs. $24,931.4 and $10,509.0 vs. $20,671.5, respectively). Similar trends were observed at 12 months, except that the 2 groups had comparable total health care costs. CONCLUSIONS: The use of dabigatran is associated with lower emergency department and all-cause hospitalization costs but greater outpatient costs in a real-world, NVAF patient population compared with warfarin.

High exposure compared with standard exposure to metoclopramide associated with a higher risk of parkinsonism: a nationwide population-based cohort study.

AIMS: We conducted a cohort study utilizing a nationwide health insurance database to assess the European Medicines Agency's restrictions on using metoclopramide and its association with the risk of parkinsonism. METHODS: New oral metoclopramide users aged ≥20 years, and age- and gender-matched non-users were recruited between 2001 and 2011. Users were divided into high-exposure (dose >30 mg day-1 and/or duration >5 days) and standard-exposure (dose ≤30 mg day-1 and duration ≤5 days) groups. The adjusted hazard ratio (aHR) with 95% confidence interval (CI) estimated the risk of parkinsonism. RESULTS: During a 1-year period, 122 of 218 931 (0.06%) users of metoclopramide vs. 56 of 218 931 (0.03%) non-users developed parkinsonism (P < 0.001). Among the 122 cases of parkinsonism in users, 64 (0.04%) were from 168 566 standard-exposure users and 58 (0.12%) from 50 365 high-exposure users. Compared with non-users, the risk of parkinsonism was higher in users (aHR 2.16; 95% CI 1.54, 3.02), including standard-exposure (aHR 1.73; 95% CI 1.11, 2.70), and high-exposure (aHR 3.15; 95% CI 1.78, 5.57) users. High-exposure users had a higher risk of parkinsonism than standard-exposure users (aHR 1.83; 95% CI 1.28, 2.63). Within the high-exposure group, 45 233 of 50 365 (89.81%) users and 55 of 58 (94.83%) parkinsonism were from long-duration exposure; 5 132 of 50 365 (10.19%) users and 3 of 58 (5.17%) parkinsonism were from high-dose exposure and long-duration + high-dose exposure. CONCLUSIONS: The risk of parkinsonism in metoclopramide users, although extremely low (0.06%), is 2.16-fold greater than in non-users. High-exposure users have a 1.83-fold higher risk than standard-exposure users. As users in high-exposure group had a higher risk of parkinsonism than in standard-exposure group, and the majority of users and parkinsonism in high-exposure group were from long-duration exposure; thus, physician are advised to avoid prescribing metoclopramide for >5 days, even if the daily dose is ≤30 mg.

Proton pump inhibitors and risk of periampullary cancers--A nested case-control study.

Considerable attention has been focused on long-term use of proton pump inhibitor (PPI) medications in relation to increased risk of cancer via stimulation of DNA-damaged cells. The aim of this study is to examine the dose-dependent effect of PPI on periampullary cancers in a national population-based cohort. A nested case-control analysis was constructed based on Taiwan's National Health Insurance Research Database and the Taiwan Cancer Registry between the years 2000 and 2010. Cases involving patients diagnosed with periampullary cancers were selected and controls were matched to cases according to age, sex and observational period. A "PPI user" was defined as any patient receiving more than 28 cumulative defined daily doses as measured by prescription drug claims. Conditional logistic regression analysis was conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) according to the level of PPI exposure. A total of 7,681 cases and 76,762 matched controls were included with a mean follow-up period of 6.6 years (SD: 2.0). The odds of PPI exposure in patients with periampullary cancers were higher than that of control patients with an adjusted OR of 1.35 (95% CIs: 1.16-1.57). Our results also showed that PPI exposure was slightly linked to periampullary cancers in dose-dependent manner. A similar association was observed in patients who solely took PPI but no eradication therapy for Helicobacter pylori infection. Long-term PPI use was associated with an increased risk of periampullary cancers in the current population-based study. Physicians must weigh potential risks of long-term maintenance against therapeutic benefit.