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Ming-Hsueh Tsai,1 Tom C Chan,2 Meng-Sui Lee,3,4 Mei-Shu Lai5 1Department of Internal Medicine, Taipei City Hospital, Taipei, Taiwan; 2Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 3Department of Dermatology, Taipei City Hospital, Taipei, Taiwan; 4Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 5Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, TaiwanCorrespondence: Meng-Sui LeeDepartment of Dermatology, Taipei City Hospital, No. 33, Sec. 2, Zhonghua Road, Taipei, 100, TaiwanTel/Fax +886 2 23889595 Ext 2225Email leemengsui@hotmail.comMei-Shu LaiInstitute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, 5Fl. No. 17, Hsu Chow Road, Taipei, 100, TaiwanTel +886 2 33668018Email mslai@ntu.edu.twPurpose: Psoriasis is an inflammatory disease associated with cardiovascular disease. Methotrexate (MTX) is a first-line systemic anti-psoriatic agent that may also protect against cardiovascular disease. We examined the cardiovascular risks among patients with psoriasis who were receiving MTX or the comparator, retinoids.Patients and Methods: We analysed data from the Taiwanese National Health Insurance database. The primary outcome was a composite of hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality (composite cardiovascular outcome). Propensity score-weighted analyses were used to evaluate patients who were followed from therapy initiation to the earliest instance of outcome occurrence, insurance disenrollment, death or study termination.Results: We identified 13,777 patients who received MTX and 6020 patients who received retinoids from 2000 to 2012. Compared to retinoids, MTX was associated with lower crude incidences of cardiovascular outcomes, hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality. In intention-to-treat analyses, MTX was associated with lower risks of composite cardiovascular outcomes (adjusted hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.76– 0.94), ischaemic heart disease (HR: 0.87, 95% CI: 0.71– 1.06), ischaemic stroke (HR: 1.06, 95% CI: 0.89– 1.27) and all-cause mortality (HR: 0.75, 95% CI: 0.66– 0.85). Similar results were found in as-treated analyses.Conclusion: In this nationwide cohort of patients with psoriasis, compared to retinoids, MTX was associated with a modestly lower risk of cardiovascular events.Keywords: cardiovascular events, inflammation, psoriasis, pharmacoepidemiology

Background Follicular lymphoma (FL) is less prevalent in Asians, but detailed epidemiological analyses were not available. This study aimed to characterize the epidemiologic features of FL in Taiwan to explore the factors relevant to disease development and prognosis. Methods We obtained epidemiological data for Taiwanese citizens during 1990‐2012 from Taiwan's National Cancer Registry Database, and the corresponding data for US Caucasians from the Surveillance, Epidemiology, and End Results Program. Changes in incidence rates were evaluated with age‐period‐cohort (APC) analyses. Patient outcomes were compared with 5‐year relative survival rates (RS) estimates. Results Incidence rates of FL in Taiwan increased continuously during the study period (0.34 to 0.91 per 100 000 person‐year from 1993‐1997 to 2008‐2012 in men, and from 0.29 [1993‐1997] to 0.81 [2008‐2012] in women), while rates in the US remained stable in both sexes, ranging between 3.73 and 3.96 in men and between 3.24 and 3.55 in women. Estimates of average annual percentage changes in incidence were significantly positive in Taiwan, but not in US Caucasians. Notably, the APC analysis identified a strong birth‐cohort effect in Taiwan, corresponding to environmental alterations present during the study period. The estimated 5‐year RS rates in both populations showed steady improvement, but the RS in Taiwanese patients was consistently 10% lower than in US Caucasians. Conclusion A distinct increasing trend of incidence with a strong birth‐cohort effect was identified in Taiwan, providing evidence of the association between environmental factors and disease development.

Background: Invasive dental treatments (IDTs) can yield temporary bacteremia and have therefore been considered a potential risk factor of infective endocarditis (IE). It is hypothesized that, through the trauma caused by IDTs, bacteria gain entry to the bloodstream and may attach to abnormal heart valves or damaged heart tissue, giving rise to IE. However, the association between IDTs and IE remains controversial. The aim of this study is to estimate the association between IDTs and IE. Methods: The data in this study were obtained from the Health Insurance Database in Taiwan. We selected 2 case-only study designs, case-crossover and self-controlled case series, to analyze the data. The advantage of these methods is that confounding factors that do not vary with time are adjusted for implicitly. In the case-crossover design, a conditional logistic regression model with exposure to IDTs was used to estimate the risks of IE following an IDT with 4, 8, 12, and 16 weeks delay, respectively. In the self-controlled case series design, a conditional Poisson regression model was used to estimate the risk of IE for the risk periods of 1 to 4, 5 to 8, 9 to 12, and 13 to 16 weeks following an IDT. Results: In total, 9120 and 8181 patients with IE were included in case-crossover design and self-controlled case series design, respectively. In the case-crossover design, 277 cases and 249 controls received IDTs during the exposure period, and the odds ratio was 1.12 (95% confidence interval, 0.94–1.34) for 4 weeks. In the self-controlled case series design, we observed that 407 IEs occurred during the first 4 weeks after IDTs, and the age-adjusted incidence rate ratio was 1.14 (95% confidence interval, 1.02–1.26) for 1 to 4 weeks after IDTs. Conclusions: In both study designs, we did not observe a clinically larger risk for IE in the short periods after IDTs. We also found no association between IDTs and IE among patients with a high risk of IE. Therefore, antibiotic prophylaxis for the prevention of IE is not required for the Taiwanese population.

Backgrounds To examine the comparative effectiveness between dual and single antiplatelet therapies in real-world, medically managed elderly patients with acute myocardial infarction (AMI). Methods This retrospective study identified very elderly (> 85 years) patients, who were medically managed, with their first AMI from the Taiwan National Health Insurance claims database from 2007 to 2010. Patients were classified as dual antiplatelet therapy (DAPT) group, aspirin only group and clopidogrel only group. Study outcomes included all-cause death, cardiovascular death and gastrointestinal bleeding. Treating DAPT group as the reference, we employed a multivariable Cox regression model to compare the relative risks of outcomes between 3 groups using pairwise comparison approach. Results Among 1469 patients with incident ST-elevation myocardial infarction (STEMI, 14%) or non-STEMI (86%), 390 patients were prescribed DAPT, 549 aspirin only, and 530 clopidogrel only. After 9 months of follow-up, aspirin only group had similar risks of all-cause death (adjusted HR 1.21, 95% CI 0.77–1.89, p = 0.41), cardiovascular death (adjusted HR 1.16, 95% CI 0.66–2.04, p = 0.60) and gastrointestinal bleeding (adjusted HR 1.66, 95% CI 0.77–3.57, p = 0.20) in comparison with DAPT group. Clopidogrel users had a higher risk of all-cause death (adjusted HR 1.50, 95% CI 1.00–2.25, p = 0.049) but similar risks of cardiovascular death and gastrointestinal bleeding when compared with DAPT. Conclusions Among very elderly patients who were medically managed after AMI, single antiplatelet therapy had comparable protective effect as DAPT. But clopidogrel only strategy was associated with a higher risk of all-cause death. Electronic supplementary material The online version of this article (10.1186/s12877-018-0777-4) contains supplementary material, which is available to authorized users.

Objective: To evaluate the influence of age, screening interval, and histologic type on the effect of Pap smears in cervical cancer screening. Materials and methods: Data were retrieved from the Taiwan National Cancer Registry and Cervical Cancer Screening Registration System for the period from 2002 to 2010. Age, Pap smear interval, FIGO stage, and histology were further analyzed. Results: A total of 12,294 women with cervical cancer were enrolled, including 10,040 with squamous cell carcinoma (SCC), 1720 with adenocarcinoma (ADC), 401 with adenosquamous carcinoma (ASC), and 133 with small cell neuroendocrine carcinoma (SMC). Women who had a Pap smear at an interval of

Asian population-based data evaluating all-cause mortality and cause-specific mortality in patients with psoriasis are limited. This study aimed to evaluate the risk of all-cause mortality (stratified according to onset status, disease severity, and concomitant psoriatic arthritis) and cause-specific mortality in patients with psoriasis. Our study cohort consisted of 80,167 patients with newly diagnosed psoriasis between 2001 and 2012 in the National Health Insurance Database. Vital status and cause of death were ascertained from the National Death Registry of Taiwan. All-cause and cause-specific crude mortality rates and standardized mortality ratios were estimated. A total of 7,198 deaths were identified during the follow-up period (508,505 person-years). The standardized mortality ratios were 1.53 for severe psoriasis (95% confidence interval = 1.45-1.60), 1.47 for early-onset psoriasis (95% confidence interval = 1.34-1.61), and 1.47 for patients with psoriatic arthritis (95% confidence interval = 1.36-1.58). In the cause-specific mortality analysis, the absolute and excess risks of death were highest for malignancies (3.6 and 1.57 deaths per 1,000 patient-years, respectively) and circulatory system diseases (3.0 and 1.44 deaths per 1,000 patient-years, respectively). Patients with severe psoriasis, early-onset psoriasis, and psoriatic arthritis had higher all-cause mortality risks. In particular, patients with psoriasis had higher excess risks of mortality from malignancies and circulatory system diseases.

Background— Extracorporeal membrane oxygenation (ECMO) provides circulatory and respiratory support for patients with severe acute cardiopulmonary failure. The objective of this study was to examine the survival outcomes for patients who received ECMO. Methods and Results— Adult patients who received ECMO from September 1, 2002, to December 31, 2012, were identified from the Taiwan National Health Insurance Database associated with coronary artery bypass graft surgery, myocardial infarction/cardiogenic shock, injury, and infection/septic shock. A Cox regression model was used to determine hazard ratios and to compare 30-day and 1-year survival rates with the myocardial infarction/cardiogenic shock group used as the reference. The mean±SD age of the 4227-patient cohort was 57±17 years, and 72% were male. The overall mortalities were 59.8% and 76.5% at 1 month and 1 year. Survival statistics deteriorated sharply when ECMO was required for >3 days. Acute (30-day) survival was more favorable in the infection/septic shock (n=1076; hazard ratio, 0.61; 95% confidence interval, 0.55–0.67), coronary artery bypass graft surgery (n=1077; hazard ratio, 0.68; 95% confidence interval, 0.61–0.75), and injury (n=369, hazard ratio, 0.82; 95% confidence interval, 0.70–0.95) groups. The extended survival rapidly approached an asymptote near 20% for the infection/septic shock, myocardial infarction/cardiogenic shock (n=1705), and coronary artery bypass graft surgery groups. The pattern of survival for the injury group was somewhat better, exceeding 30% at year-end. Conclusions— Regardless of initial pathology, patients requiring ECMO were critically ill with similar guarded prognoses. Those in the trauma group had somewhat better outcomes. Determining the efficacy and cost-effectiveness of ECMO should be a critical future goal.

Purpose Patients with psoriasis and/or psoriatic arthritis (PsA) are known to have increased cardiovascular morbidity and mortality. Hypertension, an important risk factor for cardiovascular disease, is highly prevalent in patients with psoriasis and/or PsA. The effects of anti-psoriatic medications – including cyclosporine, nonsteroidal anti-inflammatory drugs, and glucocorticoids – on hypertension remain unclear. We examined whether such medication exposure was associated with hypertension in psoriasis patients. Methods This population-based, nested case–control study analyzed data from an inception psoriasis cohort identified from Taiwan's National Health Insurance Research Database, 2000–2010. A total of 1530 patients with newly diagnosed hypertension and 4542 age- and gender-matched controls were included in the analysis. Conditional logistic regressions were applied to estimate the effects of drug of interest on hypertension. Results After adjusting for potential confounders, patients with current use of cyclosporine [odds ratio (OR) = 7.13; 95% confidence interval (CI) 1.85–27.49], nonsteroidal anti-inflammatory drugs (OR = 2.2; 95% CI 1.95–2.49), or systemic glucocorticoids (OR = 1.42; 95% CI 1.23–1.64) showed an increased risk of hypertension as compared to those not exposed to these drugs. Moreover, an increasing dose or combined use of nonsteroidal anti-inflammatory drugs and glucocorticoids was associated with increased hypertension risk. The risk of hypertension associated with glucocorticoids, or combined use was greatest among patients aged 49 years or less. Conclusions The use of cyclosporine, nonsteroidal anti-inflammatory drugs, or glucocorticoid was associated with hypertension in patients with psoriasis and/or PsA. These study results inform physicians on the importance of early identification of hypertension during therapy with such medication. Copyright © 2015 John Wiley & Sons, Ltd.

BackgroundThe long-term outcome of patients with both diabetes and schizophrenia remains unclear.AimsTo explore whether having schizophrenia increases the risk of advanced complications and mortality in people with diabetes.MethodThis is a population-based matched cohort study using Taiwan's National Health Insurance Research Database. A total of 11 247 participants with diabetes and schizophrenia and 11 247 participants with diabetes but not schizophrenia were enrolled. We used Cox proportional hazard models to determine the effect of schizophrenia on macrovascular and microvascular complications, and all-cause mortality.ResultsThe adjusted hazard ratios were 1.49 (95% CI 1.32–1.68) for macrovascular complications, 1.05 (95% CI 0.91–1.21) for microvascular complications and 3.68 (95% CI 3.21–4.22) for all-cause mortality in patients with diabetes and schizophrenia compared with those patients with diabetes but not schizophrenia.ConclusionsPatients with both diabetes and schizophrenia had an increased risk of macrovascular complications and all-cause mortality but did not have statistically significant elevated risk of microvascular complications.

Background Despite the recommendations of statins treatment for secondary prevention of atherosclerotic cardiovascular disease (ASCVD), treatment adherence and persistence are still a concern. This study examined the real world practice of long-term adherence and persistence to statins treatment initiated after hospital discharge for ASCVD, and their associated factors in a nationwide cohort. Methods Post discharge statin prescriptions between 2006 and 2012 were extracted from the Taiwan National Health Insurance claims database. Good adherence, defined as proportion of days covered (PDC) ≥0.8 and mean medication possession ratio (MPR), was measured every 180-day period. Non-persistence was defined on the date patients failed to refill statin for 90 days after the end of the last prescription. Their associations with influential factors were analyzed using a generalized estimating equation and Cox’s proportional hazard model. Results There was a total of 185,252 post-discharge statin initiations (from 169,624 patients) and followed for 467,398 patient-years in the study cohort. Percentage of good adherence (mean MPR) was 71% (0.87) at 6-months; declined to 54% (0.68), 47% (0.59), and 42% (0.50) at end of year 1, 2, and 7, respectively. Persistence in statin treatment was 86, 67, 50, and 25% at 6-month, 1-, 2-, and 7-year, respectively. Comparing the statin-cohort initiated from year 2006 to 2012, 1-year persistence increased from 58 to 73%, and 1-year good adherence improved from 45 to 61%. Factors associated with sub-optimal adherence and non-persistence included: prescription by primary care clinics or non-cardiology specialties; patients’ age > 75 years; no history of previous statin use; ASCVD events with ischemic stroke diagnosis; comorbidities of renal disease, liver disease, depression, and chronic obstructive pulmonary disease. Conclusions Despite the improving trends, long-term adherence and persistence of statin treatment were suboptimal in Taiwan. Strategies to maintain statin treatment adherence and persistence need to be implemented to further enhance the positive trend.

The overall survival (OS) of patients with ovarian cancer is poor while epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. The aim of the present study was to evaluate the clinico-pathologic characteristics, especially the prognostic factors, for patients with epithelial ovarian cancer (EOC) in Taiwan. Information about newly diagnosed patients with EOC from 2009 to 2012 was retrieved from the database of the Taiwan Cancer Registry. Data from 2009 to 2013 for the respective cases from the claims database of Taiwan's National Health Insurance and National Death Registry were then retrieved. Potential prognostic factors were analyzed. The mean age at diagnosis of the 2,498 patients was 52.8 years. Serous carcinoma and clear cell carcinoma were diagnosed in 43.3% and 22.8% of the total patients, respectively. For patients with early-stage disease, taxane-based adjuvant chemotherapy, stage I, and younger age at diagnosis led to better overall survival (p = 0.030, p = 0.002, p

Background and objective Potential hepatoxicity is an important clinical concern when administering immunosuppressive therapies to patients infected by hepatitis B virus (HBV). Tumor necrosis factor inhibitors (anti-TNF) increase the likelihood of hepatitis consequent to HBV reactivation, but reported risks and outcomes vary. We determined the risks of liver enzyme elevation in anti-rheumatic drug users from an HBV-endemic region with differing HBV serostatus. Methods We established retrospective cohorts with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis who: 1) received anti-TNF agents from 1 January 2004 to 30 June 2013; 2) received care from 1 June 2011 to 30 June 2013 but only ever used conventional disease-modifying anti-rheumatic drugs (DMARDs). Serology results defined three subgroups: HBV surface antigen positive (HBsAg+), HBsAg negative/HBV core antibody positive (HBsAg−/HBcAb+), or uninfected. We compared incidences of serum alanine aminotransferase (ALT) exceeding twice the upper reference limit between HBV serostatus subgroups in each treatment cohort. Results Among 783 patients treated with anti-TNF (n = 472) or DMARDs only (n = 311), HBsAg−/HBcAb+ anti-TNF users had incidence of ALT elevation commensurate with uninfected counterparts (6.1 vs. 6.0/100 person-years), compared to 19.6/100 person-years in HBsAg+ patients (standardized rate ratio 3.3, 95% CI 1.3–8.2); none effected had severe or fatal hepatitis and ALT levels in all HBsAg−/HBcAb+ patients remained stable, mostly normalizing spontaneously, or after moderating treatment. Patterns of of ALT elevation associated with differing HBV serostatus in the DMARD cohort, resembled those in anti-TNF users. Conclusions In this large HBV-endemic cohort, the absolute incidence of ALT elevation in anti-TNF users was more than three-fold higher in HBsAg+ patients than in uninfected counterparts; however, no such association was evident in patients with HBsAg−/HBcAb+ serotype, whose risk and outcomes of liver enzyme elevation were similar to uninfected patients, suggesting that anti-TNF use by HBsAg−/HBcAb+ patients is probably safe.

Aims This study aimed to evaluate the risk of hip/femur fractures during the initiation period of α-adrenoceptor blocker therapy using the National Health Insurance claims database, Taiwan, with a self-controlled case series design. Methods All male beneficiaries aged over 50 years as of 2007, who were incident users of α-adrenoceptor blockers and also had a diagnosis of hip/femur fracture within the 2007–2009 study period were identified. The first day when the α-adrenoceptor blocker was prescribed was set as the index date. We partitioned the initial 21 day period following the index date as the post-exposure risk period 1, days 22–60 after the index date as the post-exposure risk period 2, the 21 day period prior to the index date as the pre-exposure risk period 1 and days 22–60 prior to the index date as the pre-exposure risk period 2. The remainder of the study period was defined as the unexposed period. The incidence rate ratio (IRR) of hip/femur fractures within each risk period compared with the unexposed period was estimated using a conditional Poisson regression model. Results A total of 5875 men were included. Compared with the unexposed period, the IRR of hip/femur fractures was 1.36 (95% confidence interval 1.06, 1.74, P = 0.017) within the post-exposure risk period 1 for patients without concomitant prescriptions of anti-hypertensive agents. Conclusions Use of α-adrenoceptor blockers was associated with a small but significant increase in the risk of hip/femur fractures during the early initiation period in patients without concomitant prescriptions of anti-hypertensive agents.

Objective: Because the number of long-term survivors of colorectal cancer has increased, second primary cancer has become an important issue. However, previous studies were heterogeneous in design, and few data for Asia-Pacific area were available. Methods: This was a retrospective population-based study conducted using the national database of the Taiwan Cancer Registry. Patients who have histology-proven primary colon cancer and rectal cancer from 1995 to 2005 were enrolled in this study. All second primary cancer events had to be histology proven. The standardized incidence ratio of second primary cancer was used as an indicator. Standardized incidence ratio was counted as the number of observed second primary cancer divided by the expected number of cancer cases in the general population. Results: A total of 65 648 eligible index patients were enrolled, and 3810 second primary cancer events were identified. The standardized incidence ratio for all of the patients was 1.03 (95% confidence interval: 0.99–1.06), which implied that the risk of second primary cancer was not significantly elevated in the index patients compared with that of the general population. The standardized incidence ratio for the patients aged 70 years was 2.52 (95% confidence interval: 2.28– 2.78), 1.18 (95% confidence interval: 1.12–1.23) and 0.80 (95% confidence interval: 0.76–0.84), respectively. In young patients (aged

Background. Many studies have shown that type 2 diabetes mellitus (DM) increases the risk for several types of cancer but not cervical cancer (CC). Although DM and insulin-like growth factor 1 have preclinical and clinical implications for CC, less is known about the prognostic impact of DM on patients with early stage CC. Patients and Methods. We used the nationwide Taiwan Cancer Registry database to collect the characteristics of stage I–IIA cervical cancer patients diagnosed between 2004 and 2008. DM and other comorbidities were retrieved from the National Health Insurance database. Cervical cancer-specific survival (CSS) and overall survival (OS) times of patients according to DM status were estimated using the Kaplan-Meier method. We used a Cox proportional hazards model to calculate adjusted hazard ratios (HRs) for the effects of DM and other risk factors on mortality. Results. A total of 2,946 patients had primary stage I–IIA CC and received curative treatments, and 284 (9.6%) had DM. The 5-year CSS and OS rates for patients with DM were significantly lower than those without DM (CSS: 85.4% vs. 91.5%; OS: 73.9% vs. 87.9%). After adjusting for clinicopathologic variables and comorbidities, DM remained an independent unfavorable prognostic factor for CSS (adjusted HR: 1.46) and OS (adjusted HR: 1.55). Conclusion. In Asian patients with early cervical cancer, DM is an independent unfavorable prognostic factor influencing both OS and CSS, even after curative treatments. Implications for Practice: Type 2 diabetes mellitus (DM) increases the incidence of several types of cancer but not cervical cancer (CC); however, less is known about the impact of DM on patients who already have CC. This study suggests that DM may increase the risk of cancer recurrence and death for early stage CC patients, even after curative treatments. Incorporating DM control should be considered part of the continuum of care for early stage CC patients, and close surveillance during routine follow-up in this population is recommended.

Background The purpose of this was to find a staging strategy sensitive enough to reduce the risk of occult metastases in cN0 head and neck cancer to below 15% to 20%. Methods A total of 73 articles were selected for analysis of the diagnostic performance in staging cN0 head and neck cancer. Hypothetical estimation of negative predictive value (NPV) was calculated based on the Bayesian theory. Results The pooled estimates for sensitivity were 56.4% and 84.9% for ultrasound-guided fine-needle aspiration (FNA) and sentinel node biopsy (SNB). The pooled estimates for sensitivity were 47.0%, 56.6%, 48.3%, and 63.3% for CT, MRI, positron emission tomography (PET), and ultrasound, respectively. The pooled estimates for specificity were 88.9%, 82.5%, 86.2%, and 79.1% for CT, MRI, PET, and ultrasound. In estimation, the CT or MRI with SNB strategies had NPV higher than 85% even when the pretest metastatic rate was 60%. Conclusion The SNB procedure has the best performance. A combination of CT/MRI and SNB for cN0 head and neck cancer is preferred. © 2015 Wiley Periodicals, Inc. Head Neck, 2015

Aim To compare the cardiovascular risks associated with second-line oral antidiabetic agents added to initial metformin therapy in a large nationwide observational study. Methods We conducted a nationwide retrospective cohort study using the Taiwan National Health Insurance database. A total of 36 118 users of different add-on oral antidiabetic agents (sulphonylureas, glinides, pioglitazone, α-glucosidase inhibitors and dipeptidyl peptidase-4 inhibitors) after initial metformin therapy were included in the analysis. The reference group was sulphonylureas added to metformin, the most commonly used combination regimen. The main outcomes of interest were hospitalizations for any cardiovascular event including acute myocardial infarction, congestive heart failure and ischaemic stroke. In the main analysis, all patients were followed within their initiation groups until the study end, disregarding any changes in treatment status over time. Results In intention-to-treat analyses, there was no difference in the risk of any cardiovascular event among the add-on combination treatment groups, but significantly lower risks of acute myocardial infarction were found for the glinides plus metformin treatment group (crude hazard ratio 0.52, adjusted hazard ratio 0.39; 95% CI 0.20–0.75) and for the α-glucosidase inhibitors plus metformin treatment group (crude hazard ratio 0.63, adjusted hazard ratio 0.54; 95% CI 0.31–0.95). No difference in risk of congestive heart failure or ischaemic stroke risk was found among the combination treatment groups. In secondary as-treated analyses, similar but less significant associations were found as compared with the primary intention-to-treat analyses for all treatment groups. Conclusion There were no differences in overall cardiovascular risks among several add-on second-line oral antidiabetic agents; however, glinide plus metformin and α-glucosidase inhibitors plus metformin combination therapies might be associated with lower risks of acute myocardial infarction.

Metformin is the first-line oral therapy for type 2 diabetes with proven benefits against cardiovascular risk. Recent evidence suggested that acarbose might be similar to metformin in glucose-lowering efficacy and cardiovascular risk reduction. Therefore, international guidelines have suggested the use of acarbose as alternative first-line antidiabetic therapy.To compare the cardiovascular outcomes in the first-line users of acarbose vs metformin. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: A nationwide cohort study was conducted by analyzing the Taiwan National Health Insurance (NHI) Database. A total of 17,366 acarbose initiators and 230,023 metformin initiators were identified between January 1, 2009 and December 31, 2010. The primary outcome is hospitalization due to any cardiovascular events, including acute myocardial infarction, congestive heart failure, and ischemic stroke. The propensity score method was used to adjust for baseline differences between the two groups. Patients were followed from drug initiation to the earliest of outcome occurrence, death or disenrollment from NHI, or study termination.In intention-to-treat analyses, acarbose was associated with a higher risk of any cardiovascular event (adjusted hazard ratio [HR]: 1.05; 95% confidence interval [CI], 1.01-1.09), heart failure (HR, 1.08; 95% CI, 1.00-1.16), and ischemic stroke (HR, 1.05, 95% CI, 1.00-1.10) than metformin. No significant difference in risk was found in subgroups of patients with or without underlying hypertension, ischemic heart disease, or cerebrovascular disease. Similar results were found in auxiliary as-treated analyses or analyses stratified by propensity score quintiles.Our data do not support that acarbose has a cardio-protective effect similar to metformin as a first-line antidiabetic agent.

We performed this population-based study to investigate the effects of atorvastatin and rosuvastatin on renal function in patients with type 2 diabetes. From the Taiwan National Health Insurance Pay-for-Performance program for diabetes mellitus database, 2006 to 2009, type 2 diabetic patients aged 40 to 100 years with the first prescription of atorvastatin or rosuvastatin were identified. All the data were linked to the National Health Insurance claims database, 2000 to 2010, to construct longitudinal health care data. The Modification of Diet in Renal Disease equation was used to calculate the estimated glomerular filtration rate (eGFR), and the eGFRs between baseline and the end of follow-up (maximum 2 years) were compared. Totally, 3,601 new users of atorvastatin and 1,968 new users of rosuvastatin were included. The median follow-up was 238 days in atorvastatin users and 210 days in rosuvastatin users. The eGFR at baseline was 72.3 ± 25.9 ml/min/1.73 m(2) in atorvastatin users and 73.7 ± 27.3 ml/min/1.73 m(2) in rosuvastatin users. In both statin groups, we found no significant change in eGFR (+0.1 ml/min/1.73 m(2), 95% confidence interval -0.4 to 0.7, p = 0.62 in atorvastatin users; -0.1 ml/min/1.73 m(2), 95% confidence interval -0.8 to 0.6, p = 0.77 in rosuvastatin users). In conclusion, neither treatment with atorvastatin nor rosuvastatin was associated with a significant change of renal function in type 2 diabetic patients.

A national viral hepatitis therapy program was launched in Taiwan in October 2003. This study aimed to assess the impact of the program on reduction of end-stage liver disease (ESLD) burden. Profiles of national registries of households, cancers, and death certificates were used to derive incidence and mortality of ESLDs from 2000 to 2011. Age-gender–adjusted incidence and mortality rates of hepatocellular carcinoma (HCC) and chronic liver diseases (CLDs) and cirrhosis of adults ages 30-69 years were compared before and after launching the program using Poisson's regression models. A total of 157,570 and 61,823 patients (15%-25% of those eligible for reimbursed treatment) received therapy for chronic hepatitis B and C, respectively, by 2011. There were 42,526 CLDs and cirrhosis deaths, 47,392 HCC deaths, and 74,832 incident HCC cases occurred in 140,814,448 person-years from 2000 to 2011. Male gender and elder age were associated with a significantly increased risk of CLDs and cirrhosis and HCC. Mortality and incidence rates of ESLDs decreased continuously from 2000 to 2003 (before therapy program) through 2004-2007 to 2008-2011 in all age and gender groups. The age-gender–adjusted rate ratio (95% confidence interval; P value) in 2008-2011 was 0.78 (0.76-0.80; P

Background Angiotensin-converting enzyme (ACE) inhibitors have been widely used in the treatment of hypertension, but the comparative effectiveness in reducing mortality among different drugs is seldom reported. Methods We identified hypertensive patients who started captopril, enalapril, lisinopril, fosinopril, perindopril, ramipril, or imidapril therapy from Taiwan's National Health Insurance database between 1 January 2004 and 31 December 2009. Overall and cause-specific mortalities were ascertained through a linkage to Taiwan's National Death Registry. Patients were followed from the initiation of ACE inhibitors to death, disenrollment, or study termination (31 December 2010). A Cox proportional hazard regression model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI), using ramipril as the reference group. Results A total of 989,489 hypertensive patients were included, with a mean follow-up ranging from 3.5 years for imidapril to 4.5 years for enalapril. Captopril initiators had the highest overall mortality rate (117.8 per 1,000,000 person-days) as compared to other ACE inhibitors (54.3-79.4 per 1,000,000 person-days). Patients who started captopril therapy had a significantly increased risk of overall mortality (HR: 1.28, 95% CI: 1.24-1.31) when compared with ramipril. Enalapril (HR: 1.08, 95% CI: 1.05-1.11) and fosinopril (HR: 1.08, 95% CI: 1.05-1.12) were also associated with a modestly increased risk. No difference in mortality was found for lisinopril, perindopril, and imidapril, as compared with ramipril. Conclusions There are differences in the mortality risk associated with different ACE inhibitors. However, potential residual confounding effects might still exist.

Aim To evaluate whether aspirin can reduce the risk of colorectal cancer in people with diabetes. Methods We studied ≥ 30-year-old people with diabetes, included in the Longitudinal Health Insurance Database 2005 in Taiwan, who were treated with hypoglycaemic drugs. We used a time-varying Cox regression model to adjust for immortal time bias and to estimate the adjusted hazard ratio and 95% CI for the association between aspirin use and colorectal cancer occurrence. Results We studied a total of 60 828 people with diabetes (31 176 men and 29 652 women). Their mean (sd) age was 58.72 (13.33) years. A total of 26 494 people were taking aspirin. Aspirin use 3–5 times/week (moderate frequency) for > 5 years (long duration) was found to reduce the risk of colorectal cancer by 46% (hazard ratio 0.54, 95% CI 0.34–0.86). Aspirin use > 5 times/week (high frequency) for 4–5 years (moderate duration) and > 5 years reduced the risk of colorectal cancer by 56 and 68%, respectively (hazard ratio 0.44, 95% CI 0.24–0.80; hazard ratio 0.32, 95% CI 0.20–0.50). Low frequency (≤ 2 times/week) and/or short duration (≤ 3 years) of aspirin use did not reduce the risk of colorectal cancer. Conclusions Aspirin use with high frequency and long duration reduced the risk of colorectal cancer in people with diabetes in a frequency- and duration-dependent manner, whereas low frequency and/or short duration of aspirin use did not. The dosage, frequency and duration of aspirin use that are sufficient to prevent the incidence of colorectal cancer in people with diabetes require further study.

BACKGROUND Although irinotecan and oxaliplatin are both standard treatments for advanced colon cancer, it remains unknown whether either is effective for patients with resectable synchronous colon cancer and liver-confined metastasis (SCCLM) after curative surgery. PATIENTS AND METHODS A population-based cohort of patients diagnosed with de novo SCCLM between 2004 and 2009 was established by searching the database of the Taiwan Cancer Registry and the National Health Insurance Research Database of Taiwan. Patients who underwent curative surgery as their first therapy followed by chemotherapy doublets were classified into the irinotecan group or oxaliplatin group accordingly. Patients who received radiotherapy or did not receive chemotherapy doublets were excluded. RESULTS We included 6,533 patients with de novo stage IV colon cancer. Three hundred and nine of them received chemotherapy doublets after surgery; 77 patients received irinotecan and 232 patients received oxaliplatin as adjuvant chemotherapy. The patients in both groups exhibited similar overall survival (median: not reached vs. 40.8 months, p=0.151) and time to the next line of treatment (median: 16.5 vs. 14.3 months, p=0.349) in both univariate and multivariate analyses. Additionally, patients with resectable SCCLM had significantly shorter median overall survival than patients with stage III colon cancer who underwent curative surgery and subsequent adjuvant chemotherapy, but longer median overall survival than patients with de novo stage IV colon cancer who underwent surgery only at the primary site followed by standard systemic chemotherapy (p

Background Liver enzyme elevation is an important and common adverse effect among patients with immune-mediated diseases who receive tumour necrosis factor inhibitors (anti-TNF), and has various causes. Hence, we evaluated the relative risks of developing liver enzyme elevation in anti-TNF users with differing hepatitis B virus (HBV) infection status. Methods At a hospital in central Taiwan, 407 patients with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis received anti-TNF therapy between 1 January 2004 and 30 June 2012. We performed a nested case-control study (n = 368) of cases with serum alanine aminotransferase (ALT) > 40 international units/L ≤ 12 months after starting anti-TNF therapy, and corresponding controls without liver enzyme elevation. Conditional logistic regression was used to evaluate associations between liver enzyme elevation and HBV serostatus, as well as other risk factors. Results Thirty cases were compared to 338 controls. After adjustment for potential confounders, HBV surface antigen-positive (HBsAg+) serostatus was associated with substantially higher likelihood of developing elevated ALT (adjusted odds ratio 7.91, 95% confidence interval (CI) 2.16–31.31) relative to those with an uninfected HBV status; no such association was observed among HBsAg-negative/HBV core antibody-positive (HBsAg–/HBcAb+) patients (adjusted odds ratio 1.00, 95% CI 0.33–3.25). Increased risk of ALT elevation was associated with methotrexate used alone, without folic acid (adjusted odds ratio 11.60, 95% CI 2.52–56.46), and history of ALT elevation (adjusted odds ratio 13.71, 95% CI 4.32–45.75). Conclusions HBsAg+ patients with immune-mediated diseases who received anti-TNF therapy had an approximately eight-fold higher likelihood of liver enzyme elevation than those without HBV infection, whereas patients with HBsAg–/HBcAb+ serostatus had a risk similar to that of uninfected patients. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1413-y) contains supplementary material, which is available to authorized users.

Background: Although cancer treatment information has been collected through the Cancer Registry system in Taiwan for more than 10 years, the accuracy of such data has never been evaluated. This study examined the accuracy rate between registrar experience and on-site chart review for the first course of cancer treatment. Methods: In this retrospective chart review study, 392 randomly selected medical records from 14 hospitals were re-abstracted by experienced abstractors. The kappa coefficients of accuracy for the abstracting data were calculated against the gold standard. Correlations between registrar background and workload were then identified through regression analysis. Results: Regarding surgery type, low accuracy rates were noted for gastric cancer (84.0%), oral cavity cancer (84.6%), and bladder cancer (88.9%). For chemotherapy, low accuracy rates were observed for hematopoietic diseases (81.3%) and esophageal cancer (88.0%). For radiotherapy, low accuracy rates were noted for esophageal cancer (80.0%), cervical cancer (81.8%), and lymphoma (85.7%). When stratifying by surgery type after adjustment for hospital caseload, a high accuracy rate was found for cancer registrars who had progressed from basic to advanced licenses within 5 years of graduating. Conclusion: The accuracy rate for the first course of cancer treatment was affected by the cancer type and the experience of cancer registrars, but it was not affected by the workload of cancer registrars. We recommend that cancer registrars with basic licenses upgrade to advanced licenses as soon as possible. Medical record collaboration should establish documentation for checklist of radiotherapy and surgical operation records. Keywords: Data quality, Peer review

Background To facilitate priority-setting in health policymaking, we compiled the best available information to estimate the adult mortality (>30 years) burden attributable to 13 metabolic, lifestyle, infectious, and environmental risk factors in Taiwan. Methods We obtained data on risk factor exposure from nationally representative health surveys, cause-specific mortality from the National Death Registry, and relative risks from epidemiological studies and meta-analyses. We applied the comparative risk assessment framework to estimate mortality burden attributable to individual risk factors or risk factor clusters. Results In 2009, high blood glucose accounted for 14,900 deaths (95% UI: 11,850–17,960), or 10.4% of all deaths in that year. It was followed by tobacco smoking (13,340 deaths, 95% UI: 10,330–16,450), high blood pressure (11,190 deaths, 95% UI: 8,190–14,190), ambient particulate matter pollution (8,600 deaths, 95% UI: 7,370–9,840), and dietary risks (high sodium intake and low intake of fruits and vegetables, 7,890 deaths, 95% UI: 5,970–9,810). Overweight-obesity and physical inactivity accounted for 7,620 deaths (95% UI: 6,040–9,190), and 7,400 deaths (95% UI: 6,670–8,130), respectively. The cardiometabolic risk factors of high blood pressure, high blood glucose, high cholesterol, and overweight-obesity jointly accounted for 12,120 deaths (95% UI: 11,220–13,020) from cardiovascular diseases. For domestic risk factors, infections from hepatitis B virus (HBV) and hepatitis C virus (HCV) were responsible for 6,300 deaths (95% UI: 5,610–6,980) and 3,170 deaths (95% UI: 1,860–4,490), respectively, and betel nut use was associated with 1,780 deaths from oral, laryngeal, and esophageal cancer (95% UI: 1,190–2,360). The leading risk factors for years of life lost were similar, but the impact of tobacco smoking and alcohol use became larger because the attributable deaths from these risk factors occurred among young adults aged less than 60 years. Conclusions High blood glucose, tobacco smoking, and high blood pressure are the major risk factors for deaths from diseases and injuries among Taiwanese adults. A large number of years of life would be gained if the 13 modifiable risk factors could be removed or reduced to the optimal level. Electronic supplementary material The online version of this article (doi:10.1186/s12963-017-0134-4) contains supplementary material, which is available to authorized users.

Background In 2011, two national policies aiming to foster hospice services for terminal cancer patients took effect in Taiwan. The single-payer National Health Insurance of Taiwan started to reimburse full hospice services. The national hospital accreditation program, which graded all hospitals, incorporated hospice utilization in its evaluation. We assessed the impact of these national policies. Methods A cohort of 249,394 patients aged ≥18 years who died of cancer between 2008 and 2013 were identified from the National Death Registry. We retrieved utilization data of medical services and compared the health care utilization in the final month of life before and after the implementation of the new policies. Results After the policy changes, hospice utilization increased from 20.8% to 36.2%. In a multivariate analysis adjusting for patient demographics, cancer features, and hospital characteristics, hospice utilization significantly increased after 2011 (adjusted odds ratio [AOR] 2.35, p Conclusion The national policy changes fostering hospice care significantly increased hospice utilization, decreased invasive end-of-life care, and reduced the medical costs of terminal cancer patients.

Objectives A number of observational studies have reported that, in patients with chronic obstructive pulmonary disease (COPD), β blockers (BBs) decrease risk of mortality and COPD exacerbations. To address important methodological concerns of these studies, we compared the effectiveness and safety of cardioselective BBs versus non-dihydropyridine calcium channel blockers (non-DHP CCBs) in patients with COPD and acute coronary syndromes (ACS) using a propensity score (PS)-matched, active comparator, new user design. We also assessed for potential unmeasured confounding by examining a short-term COPD hospitalisation outcome. Setting and participants We identified 22 985 patients with COPD and ACS starting cardioselective BBs or non-DHP CCBs across 5 claims databases from the USA, Italy and Taiwan. Primary and secondary outcome measures Stratified Cox regression models were used to estimate HRs for mortality, cardiovascular (CV) hospitalisations and COPD hospitalisations in each database after variable-ratio PS matching. Results were combined with random-effects meta-analyses. Results Cardioselective BBs were not associated with reduced risk of mortality (HR, 0.90; 95% CI 0.78 to 1.02) or CV hospitalisations (HR, 1.06; 95% CI 0.91 to 1.23), although statistical heterogeneity was observed across databases. In contrast, a consistent, inverse association for COPD hospitalisations was identified across databases (HR, 0.54; 95% CI 0.47 to 0.61), which persisted even within the first 30 days of follow-up (HR, 0.55; 95% CI 0.37 to 0.82). Results were similar across a variety of sensitivity analyses, including PS trimming, high dimensional-PS matching and restricting to high-risk patients. Conclusions This multinational study found a large inverse association between cardioselective BBs and short-term COPD hospitalisations. The persistence of this bias despite state-of-the-art pharmacoepidemiologic methods calls into question the ability of claims data to address confounding in studies of BBs in patients with COPD.

Objective To measure therapeutic inertia by characterizing prescription patterns using secondary data obtained from the nationwide diabetes mellitus pay-for-performance (DM-P4P) programme in Taiwan. Methods Using reimbursement claims from Taiwan’s National Health Insurance Research Database, a nationwide retrospective cohort study was undertaken of patients with diabetes mellitus who participated in the DM-P4P programme from 2006–2008. Glycosylated haemoglobin results were used to evaluate modifications in therapy in response to poor diabetes control. Prescription patterns were used to assign patients to either a therapeutic inertia group or an intensified treatment group. Therapeutic inertia was defined as the failure to act on a known problem. Results The research sample comprised of 168 876 patients with diabetes mellitus who had undergone 899 135 tests. Of these, 37.4% (336 615 visits) of prescriptions were for a combination of two types of drug and 27.7% (248 788 visits) were for a combination of three types of drug. The proportion of patients in the intensified therapy group who were prescribed more than two types of drug was considerably higher than that in the therapeutic inertia group. Conclusion In many cases in the therapeutic inertia group only a single type of hypoglycaemic drug was prescribed or the dosage remained unchanged.

BACKGROUND Sorafenib is the current standard treatment for advanced hepatocellular carcinoma (HCC). We analyzed national prescription patterns and treatment outcomes of patients who received sorafenib for advanced HCC. PATIENTS AND METHODS We established a nation-wide cohort of patients who started receiving treatment with sorafenib for advanced HCC between August 2012 and July 2013 from the National Health Insurance Research Database of Taiwan and also retrieved demographic and prescription data. The databases of National Death Registry and Taiwan Cancer Registry were used for survival outcomes and cancer diagnosis information, respectively. RESULTS A total of 3,293 patients were enrolled. The median overall survival (OS) and time to treatment discontinuation (TTD) of all patients were 6.8 and 2.6 months, respectively. Upon the first prescription of sorafenib, 58.4% of patients received the standard dose (800 mg/day). Among them, 61.9% had subsequent dose reduction. A total of 41.6% of patients initially received lower than standard doses; 36.1% of them had subsequent dose escalation to 800 mg/day. Being male (odds ratio=1.41; p

Objectives One of the main objectives behind the expansion of insurance coverage is to eliminate disparities in health and healthcare. However, researchers have not yet fully elucidated the reasons for disparities in the use of high-cost treatments among patients of different occupations. Furthermore, it remains unknown whether discretionary decisions made at the hospital level have an impact on the administration of high-cost interventions in a universal healthcare system. This study investigated the adoption of drug-eluting stents (DES) versus bare metal-stents (BMS) among patients in different occupations and income levels, with the aim of gauging the degree to which the inclination of health providers toward treatment options could affect treatment choices at the patient-level within a universal healthcare system. Design and participants We adopted a cross-sectional observational study design using hierarchical modeling in conjunction with the population-based National Health Insurance database of Taiwan. Patients who received either a BMS or a DES between 2007 and 2010 were included in the study. Results During the period of study, 42,124 patients received a BMS (65.3%) and 22,376 received DES (34.7%). Patients who were physicians or the family members of physicians were far more likely to receive DES (OR: 3.18, CI: 2.38–4.23) than were patients who were neither physicians nor in other high-status jobs (employers, other medical professions, or public service). Similarly, patients in the top 5% income bracket had a higher probability of receiving a DES (OR: 2.23, CI: 2.06–2.47, p < .001), than were patients in the lowest income bracket. After controlling for patient-level factors, the inclination of hospitals (proportion of DES>50% or between 25% and 50%) was shown to be strongly associated with the selection of DESs (OR: 3.64 CI: 3.24–4.09 and OR: 2.16, CI: 2.01–2.33, respectively). Conclusions Even under the universal healthcare system in Taiwan, socioeconomic disparities in the use of high-cost services remain widespread. Differences in the care received by patients of lower socioeconomic status may be due to the discretionary decisions of healthcare providers.

Purpose Long-acting insulin analogues were developed to facilitate consistent glycemic control without excessive hypoglycemia. However, structural modifications of the insulin molecule can alter biological responses and binding characteristics with specific receptors. The aim of this study was to estimate the risk of sight-threatening diabetic retinopathy (STDR) associated with treatment using long-acting insulin analogues compared with intermediate-acting insulin in patients with type 2 diabetes mellitus (T2DM). Methods A retrospective cohort consisting of patients with T2DM aged 20 years of age and older with newly initiated treatment with long-acting insulin analogues (glargine and detemir) and intermediate-acting human insulin was identified from the National Health Insurance database between January 2004 and December 2006 and was subdivided into different cohorts. The risk of the development of STDR was determined by Cox regression models and compared between different cohorts. Findings Of the 46,739 eligible patients, initiators of insulin glargine, insulin detemir, and neutral protamine Hagedorn (NPH) insulin were identified for comparison using propensity-score matching methods. Long-acting insulin analogues were not associated with changed risk for STDR by intention-to-treat and time-varying use approaches between either matched or unmatched cohorts. Implications The strategies that aim at preventing diabetic retinopathy by treating T2DM patients with long-acting insulin analogues remain further prospective studies with longer follow-up period to validate our observations within an appropriate dosage range and to further evaluate the safety of long-acting insulin analogues on reducing the progression of diabetic retinopathy.

This article presents an analysis conducted on the patterns related to therapeutic inertia with the aim of uncovering how variables at the patient level and the healthcare provider level influence the intensification of therapy when it is clinically indicated. A cohort study was conducted on 899,135 HbA1c results from 168,876 adult diabetes patients with poorly controlled HbA1c levels. HbA1c results were used to identify variations in the prescription of hypoglycemic drugs. Logistic regression and hierarchical linear models (HLMs) were used to determine how differences among healthcare providers and patient characteristics influence therapeutic inertia. We estimated that 38.5% of the patients in this study were subject to therapeutic inertia. The odds ratio of cardiologists choosing to intensify therapy was 0.708 times that of endocrinologists. Furthermore, patients in medical centers were shown to be 1.077 times more likely to be prescribed intensified treatment than patients in primary clinics. The HLMs presented results similar to those of the logistic model. Overall, we determined that 88.92% of the variation in the application of intensified treatment was at the within-physician level. Reducing therapeutic inertia will likely require educational initiatives aimed at ensuring adherence to clinical practice guidelines in the care of diabetes patients.

Background. A rapid surge of young-female breast cancer (YFBC) has been observed in Taiwan and other East Asian countries. We recently reported that these cases of YFBC, in contrast to their Western counterparts, are predominantly luminal A subtype. YFBC in Asia may have distinct clinicopathological features and outcomes. Methods. Data collected prospectively by participating hospitals were retrieved from the Taiwan Cancer Database. A total of 15,881 women with newly diagnosed stage I–III breast cancer in 2002–2006 were included. The age at diagnosis was categorized into nine 5-year groups (from Results. The rates of stage I, estrogen receptor-positive (ER+), and progesterone receptor-positive breast cancer were higher in the younger patients ( Conclusion. Emerging YFBC in Taiwan is uniquely associated with favorable pathological features and better outcomes and should not be regarded as the mirror image of its Western counterpart.

Concerns about an increased cardiovascular risk with the angiotensin receptor blocker, olmesartan, prompted the current study to examine associations between olmesartan and other angiotensin receptor blockers with overall and cause-specific mortalities. We collected patients who started to use losartan, valsartan, irbesartan, candesartan, telmisartan, and olmesartan between January 1, 2004, and December 31, 2009, from Taiwan’s National Health Insurance claims database. Prescribed drug types, dosage, and other clinical information were collected. Overall mortality and cause-specific mortality were ascertained through linkages with Taiwan’s National Death Registry. Two follow-up analyses, labeled intention-to-treat and as-treated, were conducted. A Cox proportional hazard regression model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) using losartan as the reference group. A total of 690 463 subjects were included, with a mean follow-up ranging from a low of 2.8 years for olmesartan to a high of 4.1 years for irbesartan. Subjects who began with valsartan had a modest but significantly increased risk of overall mortality (HR, 1.04; 95% CI, 1.02–1.06) compared with losartan. Irbesartan (HR, 0.96; 95% CI, 0.94–0.99), candesartan (HR, 0.95; 95% CI, 0.92–0.99), telmisartan (HR, 0.93; 95% CI, 0.90–0.96), and olmesartan (HR, 0.93; 95% CI, 0.88–0.97) were associated with a slightly lower overall mortality risk than losartan. The analysis indicates that the differences in mortality risk among individual angiotensin receptor blockers were only marginal and thus less likely to be clinically important. Although uncontrolled confounding might still exist, olmesartan does not seem to increase cardiovascular risk compared with losartan.

Background The association between psoriasis and diabetes mellitus (DM) has been explored previously. However, no studies have been reported regarding the severity of psoriasis, comorbidities, and concomitant medications on the risks of DM in patients with psoriasis. Objective We sought to evaluate the impact of the severity of psoriasis, comorbidities, and concomitant medications on the risk of type 2 DM in patients with psoriasis. Methods We conducted a cohort study with 14,158 adults with psoriasis and adults without psoriasis using data from the Taiwan National Health Insurance Research Database. Cox regression models using time-varying covariates were used. Results After the comorbidities and concomitant medications were adjusted for, psoriasis was found to be independently associated with an increased risk of DM (severe: hazard ratio, 2.06 [95% confidence interval, 1.58-2.68] vs mild: hazard ratio, 1.28 [95% confidence interval, 1.05-1.55]). Other independent risk factors included age, Cushing disease, and the increased cumulative doses of the thiazide and methotrexate. Limitation The National Health Insurance Research Database did not have information regarding the Psoriasis Area and Severity Index, diet, obesity, body mass index, exercise status, and family history of diabetes. Conclusion Patients with psoriasis have a higher risk of developing DM. The risks vary depending on the severity of psoriasis, comorbidities, and concomitant medications.

Patients with Type 2 diabetes mellitus are at a higher risk of colorectal cancer (CRC). The objective of our study was to examine the inter-relationship among infection sites, systemic antibiotic use and risk of CRC among patients with Type 2 diabetes mellitus. From a diabetic cohort from the Taiwan's National Health Insurance claims database, we identified 3,593 incident colon cancer cases, 1,979 rectal cancer cases and 22,288 controls and conducted a nested case-control study to examine the association between antibiotic use and CRC incidence. Logistic regression models were applied to estimate the odds ratio (OR) and the 95% confidence interval (95% CI) between infection sites, antibiotic use and CRC incidence. Patients with intra-abdominal infection were significantly associated with increased risk for colon cancer (OR = 2.01, 95% CI = 1.73-2.35) and rectal cancer (OR = 1.59, 95% CI = 1.26-2.00). Any antianaerobic antibiotic use was associated with a higher risk of colon cancer (OR = 2.31, 95% CI = 2.12-2.52) and rectal cancer (OR = 1.69, 95% CI = 1.50-1.90) but without an obvious dose-response relationship for cumulative use. Antianaerobic antibiotics also increased the risks for those with nonintra-abdominal infection. No association was found between antiaerobic agent use and the CRC risk. The results suggest intra-abdominal infections and antianaerobic antibiotic use may be a marker for precancerous lesions or early CRC, although the possibility of antianaerobic antibiotics playing an additional role cannot be excluded. Further research examining the relationship between intra-abdominal infection, antianaerobic antibiotics use and possible change of microbiota leading to colorectal carcinogenesis is warranted.

Objective Antidepressant drugs might induce weight gain and increase diabetes risk. We examined the diabetes risk with long-term antidepressant use in a general population. Method This study was a population-based, nested case-control study using Taiwan's National Health Insurance Research Database between 1998 and 2009. A total of 47,885 patients with type 2 diabetes mellitus (ICD-9 codes: 250.x; excluding 250.x 1 and 250.x 3) and 95,770 controls were identified. We used a conditional logistic regression model for data analysis and 1-year latent period before the diabetes diagnosis to account for the quantification of treatment duration of antidepressant (defined by Anatomic Therapeutic Chemical classification code N06A). Sensitivity analyses were performed using a propensity score matching method, as well as different lengths of latent periods. Results Compared with nonusers, patients with cumulative antidepressant use (> 2 years) had an increased risk of diabetes (adjusted OR = 1.20; 95% CI, 1.05-1.37). Moreover, increasing mean daily dose or use of selective serotonin reuptake inhibitors or serotonin antagonist and reuptake inhibitors was associated with increased diabetes risk. The increased diabetes risk with long-term antidepressant therapy in patients aged 44 years or less (adjusted OR = 2.39; 95% CI, 1.46-3.90) was higher than that in older adults (adjusted OR = 1.15; 95% CI, 1.00-1.32). Conclusions The findings suggest that long-term antidepressant use may be associated with an increased risk of type 2 diabetes mellitus, especially for young adults. Therefore, long-term antidepressant use should be evaluated more cautiously for its benefits and the potential risk of diabetes.

To determine the association of neighborhood socioeconomic status (SES) with bystander-initiated cardiopulmonary resuscitation (CPR) and patient outcomes of out of hospital cardiac arrests (OHCAs) in an Asian metropolitan area.We performed a retrospective study in a prospectively collected cohort from the Utstein registry of adult non-traumatic OHCAs in Taipei, Taiwan. Average real estate value was assessed as the first proxy of SES. Twelve administrative districts in Taipei City were categorized into low versus high SES areas to test the association. The primary outcome was bystander-initiated CPR, and the secondary outcome was patient survival status. Factors associated with bystander-initiated CPR were adjusted for in multivariate analysis. The mean household income was assessed as the second proxy of SES to validate the association.From January 1, 2008 to December 30, 2009, 3573 OHCAs received prehospital resuscitation in the community. Among these, 617 (17.3%) cases received bystander CPR. The proportion of bystander CPR in low-SES vs. high-SES areas was 14.5% vs. 19.6% (p0.01). Odds ratio of receiving bystander-initiated CPR in low-SES areas was 0.72 (95% confidence interval: [0.60-0.88]) after adjusting for age, gender, witnessed status, public collapse, and OHCA unrecognized by the online dispatcher. Survival to discharge rate was significantly lower in low-SES areas vs. high-SES areas (4.3% vs. 6.8%; p0.01). All results above remained consistent in the analyses by mean household income.Patients who experienced an OHCA in low-SES areas were less likely to receive bystander-initiated CPR, and demonstrated worse survival outcomes.

The objective of this study was to use instrumental variable (IV) analyses to evaluate the clinical effectiveness of percutaneous stent revascularization versus bypass surgery in the treatment of peripheral artery disease (PAD) among type 2 diabetic patients. Type 2 diabetic patients who received peripheral artery bypass surgery (n = 5,652) or stent revascularization (n = 659) for lower extremity arterial stenosis between 2000 and 2007 were identified from the Taiwan National Health Insurance claims database. Patients were followed from the date of index hospitalization for 2 years for lower-extremity amputation, revascularization, and hospitalization for medical treatment. Analysis using treatment year, patients’ monthly income level, and regional difference as IVs were conducted to reduce unobserved treatment selection bias. The crude analysis showed a statistically significant risk reduction in favor of stent placement in lower extremity amputation and in the composite endpoint of amputation, revascularization, or hospitalization for medical treatment. However, peripheral artery stent revascularization and bypass surgery had similar risk of lower limb amputation and composite endpoints in the analyses using calendar year or patients’ monthly income level as IVs. These two treatment modalities had similar risk of lower limb amputation among DM patients with PAD.

BackgroundEvidence and treatment guidelines support the use of statins in patients with established atherosclerotic cardiovascular disease (ASCVD) for secondary prevention of subsequent cardiovascular (CV) event. However, treatment adherence and persistence are still a concern.MethodsWe constructed a retrospective population-based cohort of patients, who initiated statin treatment within 90 days after discharge from hospital for ASCVD using the claims database of Taiwan National Health Insurance. Proportion of days covered (PDC) was used to measure statin adherence, and PDC ≥80% was defined as good adherence. The study outcomes were subsequent rehospitalisation or in-hospital death due to composite ASCVD, myocardial infarction or ischaemic stroke. Their associations with statin prescription adherence or persistence were analysed using time-dependent Cox proportional hazards model.ResultsThe study cohort included 185 252 postdischarge statin initiators. There were 50 015 subsequent ASCVD rehospitalisations including 2858 in-hospital death during 7 years of study period. Good adherence was significantly associated with lower risk of ASCVD rehospitalisation (adjusted HR (aHR) 0.90; 95% CI 0.87 to 0.92) and significantly lower risk of in-hospital death (aHR 0.59; 95% CI 0.53 to 0.65). Compared with constant use of statin, patients in the three less persistent states (recent stop, non-persistence and intermittent use) were associated with higher risk of subsequent ASCVD rehospitalisation, aHRs were 1.16, 1.13 and 1.26, respectively (all pConclusionsGood adherence and persistence to statin therapy are significantly associated with lower risk of secondary ASCVD rehospitalisation and in-hospital death.

(1) Background: Overt and subclinical hypothyroidism has been associated with increased cardiometabolic risks. Here we further explore whether thyroid function within normal range is associated with cardiometabolic risk factors in a large population-based study. (2) Methods: We screened 24,765 adults participating in health examinations in Taiwan. Participants were grouped according to high-sensitive thyroid-stimulating hormone (hsTSH) level as: &lt, 50th percentile (0.47&ndash, 1.48 mIU/L, the reference group), 50&ndash, 60th percentile (1.49&ndash, 1.68 mIU/L), 60&ndash, 70th percentile (1.69&ndash, 1.94 mIU/L), 70&ndash, 80th percentile (1.95&ndash, 2.3 mIU/L), 80&ndash, 90th percentile (2.31&ndash, 2.93 mIU/L), and &gt, 90th percentile (&gt, 2.93 mIU/L). Cardiometabolic traits of each percentile were compared with the reference group. (3) Results: Elevated hsTSH levels within normal range were dose-dependently associated with increased body mass index, body fat percentage, waist circumferences, blood pressure, hemoglobin A1c (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), high homeostasis model of assessment of beta-cell (HOMA-&beta, ), triglycerides, total cholesterols, fibrinogen, and uric acids (p-for-trend &lt, 0.001), but not with fasting glucose levels. The association remained significant after adjustment of age, sex, and lifestyle. As compared to the reference group, subjects with the highest hsTSH percentile had significantly increased risk of being overweight (adjusted odds ratio (adjOR): 1.35), increased body fat (adjOR: 1.29), central obesity (adjOR: 1.36), elevated blood pressure (adjOR: 1.26), high HbA1c (adjOR: 1.20), hyperinsulinemia (adjOR: 1.75), increased HOMA-IR (adjOR: 1.45), increased HOMA-&beta, (adjOR: 1.40), hypertriglyceridemia (adjOR: 1.60), hypercholesterolemia (adjOR: 1.25), elevated hsCRP (adjOR: 1.34), increased fibrinogen (adjOR: 1.45), hyperuricemia (adjOR: 1.47), and metabolic syndrome (adjOR: 1.42), but significant risk of low fasting glucose (adjOR: 0.89). Mediation analysis indicates that insulin resistance mediates the majority of the association between thyroid hormone status and the metabolic syndrome. (4) Conclusion: Elevated hsTSH within the normal range is a cardiometabolic risk marker associated with central obesity, insulin resistance, elevated blood pressure, dyslipidemia, hyperuricemia, inflammation, and hypercoagulability.

Objectives/Hypothesis This study intends to objectively quantify and compare the regression rates of vocal lesions in patients receiving either vocal fold steroid injection (VFSI) or vocal hygiene education (VHE). Potential influence of occupational vocal demands on the treatment outcome was also investigated. Study Design Retrospective case series. Methods This study enrolled 176 patients of vocal nodules and vocal polyps. Ninety-two patients received VFSI, while 84 patients received VHE. We measured the lesion area with correction by the length of vocal fold, according to videolaryngoscopic examinations before treatment and 1 and 2 months after treatment. Results VFSI was associated with a higher lesion reduction rate than VHE at 1 and 2 months (P 0.05). In vocal polyps, the lesion reduction rate after VFSI was higher than that following VHE at 1 and 2 months (P 0.05). Conclusions VHE remains the fundamental strategy for all dysphonic patients, while VFSI can be applied alternatively. Both VFSI and VHE are effective for vocal nodules and patients with ordinary occupational vocal demands, but VFSI achieves lesion regression earlier than VHE. VFSI is preferred over VHE for vocal polyps and patients with high occupational vocal demands. Level of Evidence 4. Laryngoscope, 124:510–515, 2014

Objective: To investigate the changes of incidence and prognosis of epithelial ovarian cancer in thirty years in Taiwan. Methods: The databases of women with epithelial ovarian cancer during the period from 1979 to 2008 were retrieved from the National Cancer Registration System of Taiwan. The incidence and prognosis of these patients were analyzed. Results: Totally 9,491 patients were included in the study. The age-adjusted incidences of epithelial ovarian cancer were 1.01, 1.37, 2.37, 3.24, 4.18, and 6.33 per 100,000 person-years, respectively, in every 5-year period from 1979 to 2008. The age-specific incidence rates increased especially in serous, endometrioid and clear cell carcinoma, and the age of diagnosis decreased from sixty to fifty years old in the three decades. Patients with mucinous, endometrioid, or clear cell carcinoma had better long-term survival than patients with serous carcinoma (log rank test, p

Taiwan's Bureau of National Health Insurance launched the National Antiviral Treatment Program (NATP) in 2003 to reimburse patients for antiviral drugs and interferons for chronic hepatitis B and C. The objective was to examine the impact of the NATP on the incidence and mortality due to hepatocellular carcinoma (HCC).The cumulative numbers of NATP participants were retrieved from the National Health Insurance claims database. The national incidence and mortality rates of HCC were obtained from the Taiwan Cancer Registry in each quarter from 1979 to 2009. An interrupted time-series analysis was applied to test the temporal trend change before and after NATP.From 1979 to 1995, the HCC incidence increased in men and women of all age groups. From 2003 to 2009, 31,155 men and 10,769 women received anti-hepatitis B virus therapy, whereas 13,939 men and 10,721 women received anti-hepatitis C virus therapy. The incidence of HCC reached a plateau and then started to decline in men aged 30-39 (slope change P=0.003), 50-59 (P=0.051), and 60-69 years (P0.001). A similar trend was noted in women aged 50-59 (P=0.035), 60-69 (P=0.006), and 70-79 years (P=0.052). The HCC mortality rate had been decreasing since 1996 and a further decline was observed after 2004 in men aged 60-69 years and women aged 60-79 years.There is a strong temporal relationship between NATP and the stabilization of the HCC incidence and related mortality. The cost-effectiveness of the NATP needs further evaluation.

Background Recent studies have shown that use of angiotensin-converting enzyme (ACE) inhibitors may decrease pneumonia risk in various populations. We investigated the effect of ACE inhibitors and angiotensin II receptor blockers (ARBs) on pneumonia hospitalization in the general population of Taiwan. Methods We conducted a case-crossover study using the Taiwan Longitudinal Health Insurance Database for the year 2005. Data from patients hospitalized for the first time for pneumonia during 1997-2007 were analyzed. The case period was defined as the 30 days before admission; the periods 90 to 120 days and 180 to 210 days before admission were used as control periods. Prescribing status of ACE inhibitors and ARBs during the 3 periods was assessed for each patient. Conditional logistic regression was used to estimate the odds ratio (OR) for pneumonia associated with use of ACE inhibitors and ARBs. Results We identified 10 990 cases of hospitalization for new pneumonia. After adjustment for time-variant confounding factors, pneumonia was not associated with use of ACEI or ARBS: the ORs were 0.99 (95% CI, 0.81-1.21) and 0.96 (0.72-1.28), respectively. No association was seen for cumulative defined daily doses (DDDs), as compared with nonusers, for 0 to 30, 31 to 60, or more than 60 DDDs. The results were found to be robust in sensitivity analysis. Conclusions Neither the use nor cumulative dose of ACE inhibitors or ARBs was associated with pneumonia among the Taiwanese general population.

OBJECTIVES Emerging evidence shows that methicillin-resistant Staphylococcus aureus (MRSA) infections caused by isolates with higher vancomycin MICs within the susceptibility range are associated with adverse outcomes. No study, however, has examined different susceptibility tests in predicting treatment outcomes of MRSA infections. METHODS This retrospective cohort study included 393 patients with MRSA bacteraemia. Vancomycin MICs for all MRSA isolates were determined simultaneously by agar dilution and the Etest, and using the MicroScan, VITEK-2 and Phoenix automated systems, and categorized into low- and high-MIC isolates at a breakpoint of ≥ 2 mg/L. The essential and categorical agreement between testing methods was compared. The method-specific ability to predict in-hospital mortality was examined by multivariate logistic regression analysis controlling for other potential confounders using clinical data from 310 vancomycin-treated MRSA bacteraemia patients. RESULTS The agar dilution, Etest, MicroScan, VITEK-2 and Phoenix methods assessed 14.2% (56/393), 9.7% (38/393), 28.8% (113/393), 22.6% (89/393) and 3.1% (12/393) of MRSA isolates as having high (≥ 2 mg/L) vancomycin MICs. The essential and categorical agreement between testing methods ranged from 98.5% to 100% and from 73.8% to 91.9%, respectively. High vancomycin MICs for isolates determined using agar dilution and the Etest independently predicted mortality when controlling for confounding factors [adjusted OR, 2.321; 95% CI, 1.160-4.641; and adjusted OR, 3.121; 95% CI, 1.293-7.536, respectively]. High vancomycin MICs determined using all three automated systems failed to predict mortality. CONCLUSIONS Vancomycin MICs generated by the agar dilution and Etest methods, but not the automated systems, independently predicted mortality among vancomycin-treated MRSA bacteraemia patients. Clinicians should incorporate this information with clinical assessment for decisions on appropriate anti-MRSA treatment.

Few studies have investigated the incidence rate of lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (LPL/WM) in Asian populations. We assessed the incidence of LPL/WM using data from 13 population-based cancer registries in Japan and data from the Taiwan National Cancer registry. During 1996-2003, a total of 280 new cases of LPL/WM were recorded in Japan and 56 were recorded in Taiwan, with the median age at diagnosis being 73 and 67 years, respectively. The incidence of LPL/WM showed male predominance in both countries. Crude age-specific incidence rates increased sharply with age in both countries, especially in people >65 years. Age-standardized (to the World standard population) incidence rates per 100,000 person-years were 0.043 (0.071 for men and 0.023 for women) and 0.031 (0.041 for men and 0.020 for women) in Japan and Taiwan, respectively. Age-standardized (to the 2,000 US standard population) incidence rates in Japan and Taiwan were lower than rates reported in the literature for Asians living in the United State. A significant increasing trend was observed in the incidence over the period from 1996 to 2003 in Japan alone. This report suggests that both environmental and/or genetic factors may be involved in LPL/WM development.

Purpose Histamine-2 receptor blockers (H2RBs) might have anti-tumorogenic effect, but the clinical effect on lung cancer occurrence was unclear. Methods A total of 640,173 type 2 diabetic patients were identified from the Taiwan National Health Insurance claims database in 2000. Patients were followed from cohort entry to the earliest of cancer diagnosis, death, disenrollment from the national health insurance, or 31 December 2007. For each participant, H2RB use during the follow-up period was ascertained from the outpatient pharmacy prescription database. Patients with incident squamous cell carcinoma (SCC) and adenocarcinoma were included as cases and up to four age- and sex-matched controls were selected by risk-set sampling. Conditional logistic regression models were applied to estimate the association between H2RBs and lung cancer incidence. Results A total of 1182 incident SCC and 2345 adenocarcinoma cases were identified, and 13,108 matched controls were selected. An increased risk was observed for H2RBs use