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Determining the proportion of patients with treatment-resistant depression (TRD) among patients with unipolar depression receiving adequate pharmacological treatment (pharmaceutically treated depression [PTD]) is clinically important and may affect health care utilization. In Taiwan, these issues can be assessed by analyzing population-based data.The present study included data from the Taiwan National Health Insurance Research Database from 2010 to 2017. Among patients with depression, PTD was defined by the receipt of at least one adequate antidepressant treatment, and TRD was defined as receiving a third adequate antidepressant treatment after failure to respond to two prior treatments. Time of progression from PTD to TRD was estimated via the Kaplan-Meier function. A propensity-matched case-comparison cohort approach was used to compare resource utilization between patients with non-TRD PTD and TRD.TRD was defined in 11.2 % of patients with unipolar depression and 37.1 % of PTD patients. The time of progression from PTD to TRD was approximately 1 year. Most TRD patients were women, middle-aged, and treated in general practice clinics. Antidepressant monotherapy, followed by antidepressant with augmentation, was the most common treatment strategy applied to TRD patients. Medical utilization was significantly higher in patients with TRD than those with non-TRD PTD across most aspects.TRD was defined based on pharmacological treatment patterns, as the reasons for changes in antidepressant regimens were not available.Approximately one-third of patients with PTD developed TRD, often soon after receiving adequate pharmacological treatment. Patients with TRD used more medical resources than patients with non-TRD PTD.

Atopic dermatitis (AD) is a common chronic skin disease. Only relatively scant studies from Asian countries have attempted to quantify AD-associated healthcare utilization and costs by using population-based databases. This study aims to evaluate the AD-associated annual healthcare utilization and costs in Taiwan.A retrospective matched-cohort study was conducted by matching the AD cases with controls at a 1:4 (cases:controls) ratio, with the data for both the cases and controls being sourced from the 2017 National Health Insurance Research Database (NHIRD). The AD patients were stratified by disease severity based on their treatments. Differences in the regression-adjusted frequency of care and costs between the cases and controls were compared using t-tests by the severity level of AD.The incremental frequency of outpatient visits per year increased with AD severity (9.60, 11.28, and 16.23 for mild, moderate, and severe cases, respectively). However, the frequency of inpatient care and emergency room visits per year showed no consistent pattern associated with disease severity. The incremental total costs per year were NT$9,511.64, NT$9,705.20, and NT$15,762.09 for mild, moderate, and severe cases, respectively, and the outpatient and drug costs accounted for 46.65%-54.82% and 17.01%-31.20% of the total costs, respectively.AD was found to impose significant healthcare costs, with estimated total cost burdens of NT$3.61 billion in 2017, which is 0.314% of Taiwan's national health expenditure and 0.020% of Taiwan's gross domestic product.

To investigate the age and gender differences among chronic dialysis patients who developed genitourinary cancers in Taiwan.Incident hemodialysis patients aged 20 years or older were selected for retrospective cohort study from the National Health Insurance Research Database between 2002 and 2015, and the Taiwan Cancer Registry Database between 2007 and 2015. A two-step approach was employed to find the respective matched controls of non-dialysis patients. Finally, 65,450 dialysis patients and 261,800 non-dialysis patients were matched for further analysis. New diagnosis of genitourinary cancers during follow-up was the primary outcome of interest.Dialysis was significantly associated with increased risk of all types of genitourinary cancers (P.001), substantially within the first two years after dialysis initiation. Cox proportional hazard analysis showed a significantly increased hazard ratio (HR 6.58, 95% CI 6.05-7.16) among dialysis patients after multivariate adjustment, and the highest risk was bladder cancer (HR 7.85, 95% CI 6.97-8.84). Subgroup analysis showed younger dialysis patients (20-49 years old) had the highest risk of genitourinary cancer, especially females, in this subgroup with the highest risk of bladder cancer (HR 58.08, 95% CI 13.88-243.06).The risks of all site-specific genitourinary cancers were increased in chronic dialysis patients, especially in younger females. Developing different screening strategies for these high-risk patients is necessary.This study compared the effect of sex, age and dialysis duration on the susceptibility to develop genitourinary cancers in dialysis patients through the national health database linkage in Taiwan. We matched 65,450 dialysis patients and 261,800 non-dialysis patients for further analysis. Younger and female dialysis patients were at higher risk of kidney and bladder cancers.

Background: Aristolochic acids (AA) and arsenic are chemical carcinogens associated with urothelial carcinogenesis. Here we investigate the combined effects of AA and arsenic toward the risk of developing upper tract urothelial carcinoma (UTUC). Methods: Hospital-based (n = 89) and population-based (2,921 cases and 11,684 controls) Taiwanese UTUC cohorts were used to investigate the association between exposure to AA and/or arsenic and the risk of developing UTUC. In the hospital cohort, AA exposure was evaluated by measuring aristolactam-DNA adducts in the renal cortex and by identifying A>T TP53 mutations in tumors. In the population cohort, AA exposure was determined from prescription health insurance records. Arsenic levels were graded from 0 to 3 based on concentrations in well water and the presence of arseniasis-related diseases. Results: In the hospital cohort, 43, 26, and 20 patients resided in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Aristolactam-DNA adducts were present in >90% of these patients, indicating widespread AA exposure. A>T mutations in TP53 were detected in 28%, 44%, and 22% of patients residing in grade 0, 1+2, and 3 arseniasis-endemic areas, respectively. Population studies revealed that individuals who consumed more AA-containing herbs had a higher risk of developing UTUC in both arseniasis-endemic and nonendemic areas. Logistic regression showed an additive effect of AA and arsenic exposure on the risk of developing UTUC. Conclusions: Exposure to both AA and arsenic acts additively to increase the UTUC risk in Taiwan. Impact: This is the first study to investigate the combined effect of AA and arsenic exposure on UTUC.

The incidence rate of AL (light-chain) amyloidosis is not known in Asia. We conducted a retrospective cohort study using the Taiwan National Healthcare Insurance Research database and Death Registry to estimate incidence and all-cause case fatality rates, and characteristics of patients with AL amyloidosis in Taiwan. All patients with confirmed, newly diagnosed AL amyloidosis from 01-Jan-2016 until 31-Dec-2019 were enrolled and followed up until dis-enrolment, death or study end (31-Dec-2019). There were 841 patients with newly diagnosed AL amyloidosis with median age of 61.4 years and 58.7% were men. At diagnosis, cardiac, renal and liver-related diseases were present in 28.54%, 23.19% and 2.14% of patients, respectively. AL amyloidosis age-adjusted annual incidence was 5.73 per million population in 2016 and 5.26 per million population in 2019. All-cause case fatality ranged from 1.7 to 2.9% over the study period and was highest (~10%) in patients ≥ 80 years. Survival was significantly lower in patients with co-morbid cardiac, renal, or liver-related diseases which could indicate organ involvement. The incidence of AL amyloidosis in Taiwan appears to be similar to Western countries. The poor prognosis in patients with co-morbid diseases highlights the need for earlier diagnosis.

BackgroundLong-acting injectable (LAI) antipsychotics improve medication adherence in patients with schizophrenia and extend the duration of therapeutic drug levels but with administration of an increased dose. Real-world mortality data in patients prescribed LAIs are lacking. We conducted a population-based cohort study to estimate and compare the incidence rates of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder exposed to LAIs and oral antipsychotics.MethodsPatients with a diagnosis of schizophrenia/schizoaffective disorder between January 1, 2015 and November 30, 2019 were enrolled from the Taiwan National Health Insurance Research Database and linked to Death Registry records. Eligible patients were new antipsychotic users. Relative risks of death for each antipsychotic compared with oral paliperidone were evaluated using a Cox proportional hazard model adjusted for age, sex, Charlson Comorbidity Index, index year, bipolar or major depressive or other mood disorders, mental disorders due to drug use, and baseline hospitalization frequency.ResultsThere were 228,791.08 person-years of follow-up (mean 2.48 years). The incidence rates of all-cause death in users of LAI paliperidone administered monthly (PP1M) and every 3 months (PP3M) were 7.40/1,000 person-years (95% confidence interval 5.94–9.11) and 9.93 (5.88–15.79), respectively. The incidences of completed suicide were 2.03/1,000 person-years (1.32–2.99) and 3.10 (1.14–6.88), respectively. No significant associations were observed between PP1M and PP3M compared to oral paliperidone in incidences of all-cause death or for completed suicide.DiscussionNo increased risk of all-cause death or completed suicide was observed in users of antipsychotic LAIs, including PP1M and PP3M.

Budgetary constraints force healthcare authorities to set priorities for optimal vaccine interventions. A comprehensive decision-making tool would help inform the best combination and sequence of introduction of vaccines within constrained budgets.Looking at available vaccines against pneumococcal infections in Taiwan (10/13-valent pneumococcal conjugate vaccines [PCV10, PCV13] and 23-valent pneumococcal polysaccharide vaccine [PPV23]), a constrained optimization (CO) model was used to assess the optimal combination of vaccines in children and older adults that would maximize the quality-adjusted life years under predefined budget constraints. Scenario analyses were carried out to evaluate the impact of vaccine efficacy (VE) on the optimized solution.The CO model demonstrated that the optimal sequence of vaccine introduction was PPV23 in older adults and PCV10 in children. The optimal solution was mostly driven by the potential to reduce disease burden in the older adult population. The VE of PPV23 in older adults and the VE of PCV vaccines against serotype 19A invasive pneumococcal disease had little impact on the optimal solution.The CO approach can be used to set priorities for introducing new vaccines while maximizing health gains per age group within the constrained National Vaccine Fund for the prevention of pneumococcal disease in Taiwan.

Atopic dermatitis has a substantial impact on work and activity impairment according to studies from Western communities. Prospective studies of work productivity and activity impairment in Asian patients with atopic dermatitis are lacking. The aims of this study were to investigate the impacts of atopic dermatitis on work productivity and activity impairment among Taiwanese patients, and to stratify the analyses by disease severity. One-third of employed participants reported missing work (absenteeism) in the preceding week due to atopic dermatitis, while 88.5% of the remaining two-thirds reported impaired work effectiveness (presenteeism). In addition, 92.5% of all participants reported impaired daily activities. Overall work impairment (aggregate productivity loss from absenteeism and presenteeism) was 1.8- and 2.6-fold greater in subjects with moderate and severe atopic dermatitis, respectively, compared with those with mild atopic dermatitis. Presenteeism, but not absenteeism, contributes to the majority of total work impairment in this cohort. Daily activity impairment was 1.5-fold greater in moderate atopic dermatitis, and 2.0-fold greater in severe atopic dermatitis, compared with mild atopic dermatitis. Both work and activity impairment showed significant positive correlations with atopic dermatitis severity scores (SCORing Atopic Dermatitis; SCORAD). In conclusion, work productivity and activity impairment is significantly correlated with disease severity in this Taiwanese atopic dermatitis cohort. In order to obtain a full picture of disease burden to patients and caregivers, patients with atopic dermatitis should be monitored for disease activity as well as corresponding impacts on quality of life.

The incidence of multiple myeloma (MM) is increasing worldwide, but the rate of increase is greatest in Asia. Few data describe the epidemiology and treatment of MM in Asia. Building on a cohort study from 2007 to 2012 using the Taiwan National Healthcare Insurance Research database, we extended our analysis to estimate the disease burden and treatment patterns of patients with MM in Taiwan through 2015. A further 1664 patients with newly diagnosed MM from 2013 to 2015 (total 4387 patients from 2007 to 2015) were enrolled and followed up until death or end of the observation period (December 31, 2016), whichever occurred first. The age distribution of the 2013–2015 cohort was similar to that for previous years, but there were fewer men (52.1% versus 58.0%), and more patients had renal impairment at diagnosis (19.7% versus 16.4%). From 2007 to 2015, crude annual incidences per 100,000 population of newly diagnosed MM increased from 1.74 to 2.48 and age-adjusted incidences from 1.41 to 1.65. Crude all-cause mortality rates increased over time. Case fatality decreased from 25.5 to 18.3% and median survival increased from 2.10 to 3.12 years. From 2007 to 2015, the percentage of patients receiving first-line therapy with novel agents increased from 0.4 to 89.4%, autologous stem cell transplantation doubled, and chemotherapy use decreased by 81%. Comprehensive national data covering 9 years of follow-up demonstrate continuing change in the disease burden, treatment, and survival of MM in Taiwan. Despite increased use of new treatments, MM remains largely incurable. Electronic supplementary material The online version of this article (10.1007/s00277-019-03858-w) contains supplementary material, which is available to authorized users.

Aims: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This analysis investigated the cost-effectiveness of the second-line treatment with tofacitinib, ...

Objective: Three vaccines are available to Taiwanese young girls for cervical cancer (CC) prevention. Here we evaluate the cost-effectiveness of the two-dose (2D) AS04-adjuvanted HPV-16/18 vaccine (2D-AS04-HPV- 16/18v)+screening compared with a screening programme alone, with 2D human papillomavirus 6/11/16/18 vaccine (2D-4vHPVv)+screening, and with 2D/three-dose (3D) human papillomavirus 6/11/16/18/31/33/45/52/58 vaccine (9vHPVv)+screening, for Taiwan universal mass vaccination. Methods: A static Markov cohort model simulated the natural history of human papillomavirus (HPV) infection and CC screening for a 12-year-old cohort of Taiwanese girls (N=120,000). The model ran in 1-year cycles over the cohort’s lifetime. Vaccine efficacy irrespective of HPV type was considered in the analysis for each vaccine. Input data were obtained from published literature, local databases, government reports and websites, and expert opinion. The analysis incorporated direct medical costs only, with an annual discount rate of 3.0%. The threshold was determined as 1 Gross Domestic Product per capita (New Taiwan dollar [NT$] 727,818; year 2016). Results: The 2D-AS04-HPV-16/18v+screening yielded 0.0365 quality-adjusted life year (QALY) gained at an additional cost of NT$ 5,770 per person compared with the screening programme alone. This resulted in an incremental cost-effectiveness ratio well below the threshold. Compared with 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening, discounted results demonstrated additional QALYs gained at lower cost for 2D-AS04-HPV- 16/18v+screening, making it dominant over both 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening. Conclusions: Vaccinating Taiwanese girls with 2D-AS04-HPV-16/18v in addition to screening to prevent CC is cost-effective compared with using a screening programme alone and the dominant option compared with 2D-4vHPVv+screening and 2D/3D-9vHPVv+screening.

To evaluate the ramifications of steroid use during postarrest care.Retrospective observational population-based study enrolled patients during years 2004-2011 with 1-year follow-up.Taiwan National Health Insurance Research Database.Adult nontraumatic cardiac arrest patients in the emergency department, who survived to admission.These patients were classified into the steroid and nonsteroid groups based on whether steroid was used or not during hospitalization. A propensity score was used to match patient underlying characteristics, steroid use prior to cardiac arrest, the vasopressors, and shockable rhythm during cardiopulmonary resuscitation, hospital level, and socioeconomic status.There were 5,445 patients in each group after propensity score matching. A total of 4,119 patients (75.65%) in the steroid group died during hospitalization, as compared with 4,403 patients (80.86%) in the nonsteroid group (adjusted hazard ratio, 0.74; 95% CI, 0.70-0.77; p0.0001). The mortality rate at 1 year was significantly lower in the steroid group than in the nonsteroid group (83.54% vs 87.77%; adjusted hazard ratio, 0.73; 95% CI, 0.70-0.76; p0.0001). Steroid use during hospitalization was associated with survival to discharge, regardless of age, gender, underlying diseases (diabetes mellitus, chronic obstructive pulmonary disease, asthma), shockable rhythm, and steroid use prior to cardiac arrest.In this retrospective observational study, postarrest steroid use was associated with better survival to hospital discharge and 1-year survival.

BACKGROUND Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. The chemotherapy regimens and their efficacy in practice are seldom reported. We aimed to investigate treatment patterns and survival outcomes of patients with SCLC in Taiwan. METHODS Patients newly diagnosed with SCLC from 2011 to 2015 were identified from the Cancer Registry database. Their clinical characteristics, treatment regimens, and survival status were obtained from National Health Insurance Research database. The Kaplan-Meier method and Cox-proportional hazard model were used to analyze the survival outcomes. RESULTS Among a total of 2707 patients enrolled, 439 were in the limited stage (LS, 16.22%) and 2268 were in the extensive stage of the disease (ES, 83.78%). The median age was 66 and the majority were male (90.36%). The first-line regimen used for the patients was etoposide/cisplatin-based treatment, followed by etoposide/carboplatin-based regimen, and etoposide only. The median overall survival (OS) was 16.92 months (95% confidence interval [CI] 15.31-18.92) and 8.71 months (95% CI 8.38-9.07) in LS and ES patients, respectively. Chemotherapy regimen, Eastern Cooperative Oncology Group performance status, and history of radiotherapy were significant factors associated with OS. On the other hand, the major second-line treatment was a topotecan-based regimen (68.3%). However, this showed inferior survival outcome compared to etoposide-based regimen (5.09 months [95% CI 4.76-5.62] versus 8.77 months [95% CI 6.31-11.89], p < 0.001). CONCLUSION Etoposide is the preferred and superior first-line chemotherapy regimen in combination with platinum, and an alternative choice of second-line regimen for Taiwanese patients with SCLC.

Objectives This study assessed risk adjustment performance of six comorbidity indices in two categories of comorbidity measures: diagnosis-based comorbidity indices and medication-based ones in patients with chronic obstructive pulmonary disease (COPD). Methods This was a population–based retrospective cohort study. Data used in this study were sourced from the Taiwan National Health Insurance Research Database. The study population comprised all patients who were hospitalized due to COPD for the first time in the target year of 2012. Each qualified patient was individually followed for one year starting from the index date to assess two outcomes of interest, medical expenditures within one year after discharge and in-hospital mortality of patients. To assess how well the added comorbidity measures would improve the fitted model, we calculated the log-likelihood ratio statistic G2. Subsequently, we compared risk adjustment performance of the comorbidity indices by using the Harrell c-statistic measure derived from multiple logistic regression models. Results Analytical results demonstrated that that comorbidity measures were significant predictors of medical expenditures and mortality of COPD patients. Specifically, in the category of diagnosis-based comorbidity indices the Elixhauser index was superior to other indices, while the RxRisk-V index was a stronger predictor in the framework of medication-based codes, for gauging both medical expenditures and in-hospital mortality by utilizing information from the index hospitalization only as well as the index and prior hospitalizations. Conclusions In conclusion, this work has ascertained that comorbidity indices are significant predictors of medical expenditures and mortality of COPD patients. Based on the study findings, we propose that when designing the payment schemes for patients with chronic diseases, the health authority should make adjustments in accordance with the burden of health care caused by comorbid conditions.

We aimed to evaluate factors influencing the outcomes of patients with platinum-sensitive recurrent epithelial ovarian carcinoma (EOC). Patients with advanced-stage EOC, who received debulking surgery and adjuvant chemotherapy for recurrence, were obtained from the National Health Insurance Research database of Taiwan between 2000 and 2013. A total of 1038 patients with recurrent advanced-stage EOC were recruited. The platinum + paclitaxel (PT) group had the best five-year overall survival (OS) compared with the other three groups (p &lt, 0.001). The hazard ratios (HRs) of five-year OS for the platinum + liposomal doxorubicin (PD), topotecan (TOP), and pegylated liposomal doxorubicin (PLD) groups were 1.21 (p = 0.07), 1.35 (p = 0.016), and 1.80 (p &lt, 0.001), respectively, compared with the PT group. The PT group also had lower hazard ratios of five-year OS for patients with platinum therapy-free interval (TFIp) between 6 and 12 months compared with the other three groups (p &lt, 0.0001). However, the HRs of five-year OS did not differ between the PT and PD groups in patients with TFIp &gt, 12 months. Patients with TFIp &gt, 12 months had lower HRs of five-year OS compared with those with TFIp of 6–12 months, regardless of whether they were treated with platinum-based (p = 0.001) or non-platinum-based (p = 0.003) regimens. Chemotherapeutic regimens and TFIp influenced the outcomes of patients with recurrent EOC. For patients with TFIp of 6–12 months, the PT regimen is the first choice based on their best overall survival result. For patients with TFIp &gt, 12 months, either platinum-based or non-platinum regimens could be used because of their similar excellent overall survival.

Limited real-world data are available regarding treatment practices and outcomes of multiple myeloma (MM) in Asia. We conducted a retrospective cohort study using the Taiwan National Healthcare Insurance Research database and Taiwan Death Registry and used a Markov model to describe disease progression and outcomes in 4092 patients newly diagnosed with MM from 01-Jan-2007 to 31-Dec-2015. We observed marked differences in the characteristics, length and outcome of the clinical journey between patients who did/did not receive autologous stem cell transplant, and between patients initiated on novel agents versus other treatment regimens. In transplant recipients, initiation with combined thalidomide + bortezomib increased over time (12.2–77.5%). Progression-free survival after first-line treatment improved and a lower percentage of patients died. Lenalidomide in second and third-line regimens increased (15.5–31.5%). In non-transplanted patients, initiation with novel agents increased (17.5–54.6%), but death rates remained high (60.3%). The treatment landscape of MM in Taiwan has evolved, with increased use of combined bortezomib + thalidomide for first-line and lenalidomide for second/third-line but many patients die before receiving second-line treatment. Novel agents with different modes of action should be used as early as possible to maximize their benefits. Improved MM treatments remains a critical medical need.

Background/Purpose: Atopic dermatitis (AD) is a common skin disease. At present, there is little evidence regarding its impact on patients' health-related quality of life (HRQoL) in Taiwan. Therefore, this study investigated the relationship between AD severity and patients’ HRQoL in Taiwan. Methods: Patients with AD were recruited from three hospitals in Taiwan from April 2018 to April 2019. AD severity was measured using the Scoring of AD (SCORAD) scale, and HRQoL was assessed using the Dermatology Life Quality Index (DLQI) and the five-level version of EuroQol five-dimension questionnaire (EQ-5D-5L). Results: A total of 200 patients (mean age: 34.4 years) were recruited, including 103 males and 97 females. They were further classified as 79 mild, 72 moderate, and 58 severe AD patients according to their SCORAD scores. There was a positive correlation between their SCORAD and DLQI scores (Spearman's r = 0.77, p

Longer survival in patients with multiple myeloma (MM) after treatment with novel agents (NA) such as thalidomide, bortezomib, and lenalidomide may be associated with increased risks of developing second primary malignancies (SPM). Few data describe the risk of SPM in patients with MM in Asia. This population-based retrospective cohort study assessed the risk of SPM in MM using the Taiwan National Cancer Registry and National Health Insurance Research databases from 2000 to 2014. Among 4,327 patients with newly diagnosed MM initiated with either novel agents alone (NA), chemotherapy combined with novel agents (CCNA), or chemotherapy alone (CA), the cumulative incidence of SPM overall was 1.33% at year 3. The SPM incidence per 100 person-years (95% confidence interval [CI]) was 0.914 (0.745–1.123) overall, 0.762 (0.609–1.766) for solid tumours, and 0.149 (0.090–0.247) for haematological malignancies. We compared risks of SPM using a cause-specific Cox regression model considering death as a competing risk for developing SPM. After controlling for age, gender, Charlson Co-morbidity Index, and time-period, the risk of developing any SPM or any haematological malignancy was significantly reduced in patients initiated on NA (2010–2014 period) compared to chemotherapy alone (adjusted hazard ratio 0.24, 95% CI 0.07–0.85, and 0.10, 95% CI 0.02–0.62, respectively). Contemporary treatment regiments using NA (mainly bortezomib) were associated with a lower risk for a SPM in comparison with CA.

Objective To investigate the safety of adenoidectomy and risk factors of re-adenoidectomy, and intend to provide evidence-based information to clinicians for further consideration. Methods and materials This study was based on data obtained from Taiwan’s National Health Insurance Research Database from the period 2002–2011. We utilized that data from the hospitalization group and collected information regarding those individuals who accepted adenoidectomy with or without tonsillectomy and post-adenoidectomy bleeding. Thereafter, we performed univariate and multi-variate analysis to explore the possible risk factors of re-adenoidectomy. Results A total of 5435 individuals who accepted a first adenoidectomy with or without tonsillectomy were collected. After further tracing treatment of these individuals, 107 (1.97%) accepted the revision adenoidectomy until 2011. Post-op bleeding was approximately 0.28%. The revision rate associated with patient age showed the following: 0–4 years (0.61%), 4–12 years (2.06%) and 12–18 years (2.56%). The revision rate associated with surgeon age showed: 28–41 years (1.42%), 41–50 years (2.96%), 50–65 years (2.74%); the surgeons’ surgery volume showed low (4.34%), medium (0.71%), and higher (1.02%). There are 4 diseases (otitis media with effusion, sinusitis, chronic pharyngitis, and sleep disorder) that showed a significant relationship with the revision rate when subject to univariate and multivariate analysis. The revision rate incorporating hospital locations, volumes and levels revealed no significant difference with each other. Conclusions Adenoidectomy is a generally safe surgical procedure, with low complication and low revision rate. Our study indicated that the revision rate of adenoidectomy might be lower when performed by young visiting staff with medium to higher surgical volume in the medium to higher volume hospital. If patients had diseases such as otitis media with effusion, sinusitis, chronic pharyngitis, and sleep disorder, they would be subject to higher rate of re-adenoidectomy. Surgeons should be aware and sufficiently explain this information to the parents before surgery.

Although the incidence of multiple myeloma (MM) in Asia is lower than in Western countries, it is steadily increasing. However, limited data are available that describe the epidemiology of MM in Asia.We conducted a retrospective cohort study using the Taiwan National Healthcare Insurance Research database to estimate the disease burden and clinical characteristics of patients with MM in Taiwan. All newly diagnosed confirmed MM patients during 2007-2012 were enrolled. Patients were followed up until death or end of the observation period (December 31, 2013), whichever occurred first.A total of 2723 newly diagnosed MM patients were included in the cohort analysis, of whom 58.0% (1578/2723) were men. The average age of MM patients was 67.6 years. At the time of diagnosis, the mean Charlson Comorbidity Index was 1.8, 35.3% of patients had anemia, 18.0% had bone fracture, 16.4% had renal disease and 17.3% had pneumonia. The crude annual incidence of newly diagnosed MM increased from 1.74 per 100 000 population in 2007 to 2.27 per 100 000 population in 2012 (p 0.0001), and the age-adjusted incidence from 1.41 to 1.59 per 100 000 population (p = 0.01). The use of novel treatments expanded over the study period. The crude and age-adjusted annual MM mortality rate did not change significantly over time. Case fatality decreased from 25.5% in 2007 to 19.4% in 2012 (p 0.0001).The age-adjusted incidence of MM in Taiwan increased by 13% between 2007 and 2012. Despite the introduction of new treatments, MM remains largely incurable with 19.4% mortality.

Background There is still significant uncertainty as to whether market competition raises or lowers clinical quality in publicly funded healthcare systems. We attempted to assess the effects of market competition on inpatient care quality of stroke patients in a retrospective study of the universal single-payer health insurance system in Taiwan. Methods In this 11-year population-based study, we conducted a pooled time-series cross-sectional analysis with a fixed-effects model and the Hausman test approach by utilizing two nationwide datasets: the National Health Insurance Research Database and the National Hospital and Services Survey in Taiwan. Patients who were admitted to a hospital for ischemic or hemorrhagic stroke were enrolled. After excluding patients with a previous history of stroke and those with different types of stroke, 247 379 ischemic and 79 741 hemorrhagic stroke patients were included in our analysis. Four outcome indicators were applied: the in-hospital mortality rate, 30-day post-operative complication rate, 14-day re-admission rate and 30-day re-admission rate. Results Market competition exerted a negative or negligible effect on the medical care quality of stroke patients. Compared to hospitals located in a highly competitive market, in-hospital mortality rates for hemorrhagic stroke patients were significantly lower in moderately (β = -0.05, P < 0.01) and less competitive markets (β = -0.05, P < 0.01). Conversely, the impact of market competition on the quality of care of ischemic stroke patients was insignificant. Conclusions Simply fostering market competition might not achieve the objective of improving the quality of health care. Other health policy actions need to be contemplated.

Glucocorticoids (GCs) are commonly used in breast cancer patients to ameliorate emesis induced by chemotherapy. Some preclinical studies have suggested that systemic GCs might promote survival of estrogen receptor (ER)-negative breast cancer cells. This study aims to clarify their clinical effect on patient survival. A total of 18,596 women with newly diagnosed stage I–III breast cancer in 2002–2006 were identified from the Taiwan Cancer Database and drug treatment was examined from the Taiwan National Health Insurance Claims Database. Of these, 3989 who did not receive adjuvant chemotherapy (non-chemotherapy cohort) and 3237 patients who received six cycles of adjuvant anthracycline-based chemotherapy (anthracycline cohort) were included. The impact of GC use on survival was analyzed separately in these two cohorts using Cox proportional hazards models. In the non-chemotherapy cohort, GC use was associated with aggressive clinicopathological features of breast cancer. High-dose GC was associated with shorter overall survival in univariate analysis but not in multivariate analysis. In the anthracycline cohort, multivariate analysis showed that GC use at each dose level was significantly associated with longer breast cancer-specific survival (HR 0.65, 0.70, and 0.70 for low-dose, median-dose, and high-dose GC, respectively) and overall survival (HR 0.72, 0.76, and 0.73, respectively) when compared with those receiving no GC. The associations were significant in both ER-positive and ER-negative subgroups for breast cancer-specific survival, and in ER-negative subgroup for overall survival. Concomitant use of GC improved survival in patients receiving adjuvant anthracycline-based chemotherapy for stage I–III breast cancer.

AIM Pain assessment and management have been important criteria in hospital accreditation in Taiwan since 2007. We used a Taiwanese health insurance database to determine factors influencing patterns of strong opioid use in cancer patients in their final 12 months of life. METHODS Data from patients with cancer in Taiwan outpatient clinics with cancer-related deaths between 2008 and 2011 were included in the analysis. Strong opioid prescription data from the last 12 months of each patient's life, as well as patient, physician, and hospital characteristics, were collected from the National Health Insurance Research Database. RESULTS Among 162 679 patients, more were male (63.6%) than female (36.4%) and almost half (49.3%) were ≥70 years old. Most (44.9%) patients had gastrointestinal cancer. More than one-third (35.4%) of patients were prescribed strong opioids during the 12 months before death, and more than half (53.2%) of those prescribed opioids received them in the 3 months before death. Median duration of strong opioid use was 81 days before death. Patients with head/neck cancer (52.8%) or who were treated in hematology and oncology departments (45.8%) were most likely, and patients with gastrointestinal cancer (hazard ratio = 0.65; 95% confidence interval, 0.64-0.67) or treated in gastroenterology departments (hazard ratio = 0.88; 95% confidence interval, 0.84-0.93) were least likely to be prescribed strong opioids. CONCLUSION Strong opioid prescriptions varied among patients with different cancer diagnoses and physicians. Information from this study can guide efforts to improve patient and physician education about cancer pain management.

To better understand the economic burden of gout patients in Taiwan, a nationwide retrospective study was conducted to compare the healthcare costs and utilization between gout and gout-free patients.The Longitudinal Health Insurance Database (LHID) 2010 was used to identify gout cases and matched gout-free controls. Gout cases were defined as having (1) at least three instances of diagnoses of gout on medical claims, or (2) one diagnosis of gout with at least one gout-related pharmacy claim in 2011. A control cohort was matched with cases at a 3:1 ratio by age, gender, residential area, and the Charlson Comorbidity Index. All medical utilization and costs per patient within the 365 days following the index date were compared between cases and controls.Out of 993,332 beneficiaries, a total of 21,376 matched gout patients met the gout inclusion criteria. Compared to controls, gout patients had more outpatient visits (mean = 31.2 vs 22.6), inpatient visits (mean = 1.7 vs 1.5), and ER visits (mean = 1.9 vs 1.7) (all p .0001), as well as more outpatient costs (median = USD $634 vs $404), inpatient costs (median = USD $1330 vs $1254), and ER costs (median = USD $87 vs $89) (all p .05).Gout patients had higher medical utilization and costs than gout-free patients. In gout patients, all-cause and gout-related utilization were mostly outpatient visits, whereas most of the all-cause and gout-related costs were due to hospitalization. The study findings could be useful for future economic evaluations and healthcare resource allocation.

Background Comprehensive data regarding the epidemiology of chronic urticaria (CU) in general populations are scant. Objectives To investigate the prevalence, incidence, and comorbidities of CU in general population. Methods The data were sourced from the National Health Insurance Research Database (NHIRD) for 2009–2012. Patients who had a primary/secondary ICD-9-CM diagnosis code of 708.1, 708.8, or 708.9 during the year with at least two outpatient visits and an antihistamine prescription, were identified as the cases of CU for each year. The incidence, persistence and comorbidities of CU were examined. Results The prevalence of CU ranged from 0.69% to 0.79% for each year from 2009 to 2012, and the incidence was around 0.50% per year from 2010 to 2012. Comparing to the Standard Population, the standardized prevalence ratios (SPRs) for the rheumatic diseases, thyroid disorders, inflammatory diseases, and psychiatric disorders among CU patients were 2.74, 1.81, 1.57 and 1.87, respectively. Conclusion The prevalence of CU in Taiwan is about 0.69-0.79%. CU is associated with a significantly increased risk of psychiatric disorders, inflammatory diseases, thyroid disorders, and rheumatic diseases. Except for thyroid disorders, the prevalence of these comorbidities tends to increase the longer CU persists.

Disease-related malnutrition is highly prevalent, and has prognostic implications for patients with chronic kidney disease (CKD); however, few studies have investigated the impact of malnutrition, or protein-energy wasting (PEW), on healthcare utilization and medical expenditure among CKD patients.Using claim data from the National Health Insurance in Taiwan, this study identified patients with CKD between 2009-2013 and categorized them into those with mild, moderate, or severe CKD. Cases with PEW after CKD was diagnosed were propensity-score matched with controls in a 1:4 ratio. Healthcare resource utilization metrics were compared, including outpatient and emergency department visits, frequency and duration of hospitalization, and the cumulative costs associated with different CKD severity.From among 347,501 CKD patients, eligible cohorts of 66,872 with mild CKD (49.2%), 27,122 with moderate CKD (19.9%), and 42,013 with severe CKD (30.9%) were selected. Malnourished CKD patients had significantly higher rates of hospitalization (p .001 for all severities) and re-admission (p = .015 for mild CKD, p = .002 for severe CKD) than non-malnourished controls. Cumulative medical costs for outpatient and emergency visits, and hospitalization, were significantly higher among all malnourished CKD patients than non-malnourished ones (p .001); total medical costs were also higher among malnourished patients with mild (62.9%), moderate (59.6%), or severe (43.6%) CKD compared to non-malnourished patients (p .001).In a nationally-representative cohort, CKD patients with PEW had significantly more healthcare resource utilization and higher aggregate medical costs than those without, across the spectrum of CKD: preventing PEW in CKD patients should receive high priority if we would like to reduce medical costs.

Terminating ventricular fibrillation (VF) or pulseless ventricular tachyarrhythmia (VT) is critical for successful resuscitation of patients with shockable cardiac arrest. In the event of shock-refractory VF, applicable guidelines suggest use of anti-arrhythmic agents. However, subsequent long-term outcomes remain unclear. A nationwide cohort study was therefore launched, examining 1-year survival rates in patients given amiodarone and/or lidocaine for cardiac arrest.Medical records accruing between years 2004 and 2011 were retrieved from the Taiwan National Health Insurance Research Database (NHIRD) for review. This repository houses all insurance claims data for nearly the entire populace (99%). Candidates for study included all non-traumatized adults receiving DC shock and cardiopulmonary resuscitation immediately or within 6h of emergency room arrival. Analysis was based on data from emergency rooms and hospitalization.One-year survival rates by treatment group were 8.27% (534/6459) for amiodarone, 7.15% (77/1077) for lidocaine, 11.10% (165/1487) for combined amiodarone/lidocaine use, and 3.26% (602/18,440) for use of neither amiodarone nor lidocaine (all, p0.0001). Relative to those given neither medication, odds ratios for 1-year survival via multiple regression analysis were 1.84 (95% CI: 1.58-2.13; p0.0001) for amiodarone, 1.88 (95% CI: 1.40-2.53; p0.0001) for lidocaine, and 2.18 (95% CI: 1.71-2.77; p0.0001) for dual agent use.In patients with shockable cardiac arrest, 1-year survival rates were improved with association of using amiodarone and/or lidocaine, as opposed to non-treatment. However, outcomes of patients given one or both medications did not differ significantly in intergroup comparisons.

This study investigated the risk of non-melanoma skin cancer (NMSC) in pre-dialysis patients with chronic kidney disease (CKD) and explored associated risk factors. A population-based cohort of 1,515,858 Taiwanese CKD patients was included. The standardized incidence ratio (SIR) for incident NMSC was determined. Compared with the general population, a 1.14-fold risk of NMSC was found in the CKD cohort. NMSC risk was significant in patients with pre-dialysis stage 5 CKD and anaemia (1.48-fold), and in those with uraemic pruritus after long-term antihistamine treatment (1.38-fold). A higher SIR for NMSC was found in younger patients with CKD (age

This study investigated the predominant skin cancer subtype among organ transplant recipients, patients on chronic dialysis, and patients with chronic kidney disease in Asian subjects. Among 23,644 patients with skin cancer, identified from Taiwan Cancer Registry Database, 53 were organ transplant recipients, 255 were on chronic dialysis, 1,792 had chronic kidney disease, and 21,544 were in the control group. The proportions of squamous cell carcinoma were 52.8%, 47.8%, 40.1%, and 33.5%, respectively. Compared with the control group, organ transplant recipients (1.99-fold) and patients on chronic dialysis (1.25-fold) were at higher risk of developing squamous cell carcinoma than other skin cancers after adjustment for potential confounders. Subgroups or covariates associated with increased squamous cell carcinoma compared with other skin cancer risk included patients with chronic kidney disease aged < 70 years (vs. control group; 1.3-fold), old age (vs. young age; 2.8-fold), male sex (vs. female sex; 1.1-fold), and south Taiwan residency (vs. north Taiwan residency; 1.1-fold). Organ transplant recipients and patients on chronic dialysis had immune dysregulation, resulting in a higher risk of squamous cell carcinomas.

BACKGROUND The prevalence of psychiatric comorbidities in patients with chronic urticaria (CU) in a national population is largely unknown. OBJECTIVES To investigate the prevalence of psychiatric disorders and psychiatric medication use in patients with CU in Taiwan. METHODS Data were sourced from Taiwan's National Health Insurance Research Database for 2011. Patients who had a primary/secondary International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code of 708·1, 708·8 or 708·9 during 2011 with at least two outpatient visits and an antihistamine prescription were identified as CU cases. Patients with CU were classified into three disease severity groups according to their medication types. Psychiatric disorders were identified by patients having three outpatient visits with a primary or secondary diagnosis of a given psychiatric disease. Psychiatric medication use was defined by having at least four outpatient visits with prescriptions for anxiolytics, antidepressants or sleeping pills in 2010 or 2011. RESULTS Of the 167 132 patients with CU, 82·5% had mild CU, 17·0% had moderate CU and 0·4% had severe CU. Patients with CU had a higher prevalence of psychiatric disorders and psychiatric medication prescription than control groups. The relative risk (RR) of psychiatric disorders was 1·43 for patients with mild, 1·50 for patients with moderate and 2·32 for patients with severe CU vs. the controls (P < 0·001). For psychiatric medication prescription, the RRs were 1·95, 2·70 and 2·09, respectively, vs. controls (P < 0·001). CONCLUSIONS Patients with CU had a higher prevalence and risk of psychiatric disorders and psychiatric medication prescription than control groups. What's already known about this topic? Previous studies have shown a high prevalence of psychiatric comorbidities in patients with chronic urticaria (CU), with rates ranging from 35% to 60%. Anxiety, depression and somatoform disorders have been reported as the most prevalent mental disorders in patients with CU. What does this study add? Patients with CU had a higher prevalence of psychiatric disorders and psychiatric medication use than control groups in the general population. The relative risk (RR) of psychiatric disorders was 1·43 for those with mild CU, 1·50 for those with moderate CU and 2·32 for those with severe CU vs. controls. The RR for psychiatric medication use was 1·95 for those with mild CU, 2·70 for those with moderate CU and 2·09 for those with severe CU vs. controls. Mental health evaluations and management are important elements in CU management.

This study aimed to assess the associations between the use of different types of antidepressants and health service utilization and costs among depressed patients. Data used in this study were retrieved from the Taiwan National Health Insurance Research Database. We identified 447 411 new antidepressant users during the study period (2011-2015) and they were individually followed for a 1-year period. Two-part generalized estimating equation models were conducted. Results demonstrated that there was a substantial decrease in outpatient service utilized by patients undertaking serotonin antagonists and reuptake inhibitors (β = -0.2074), serotonin-norepinephrine reuptake inhibitors (β = -0.0452), tricyclic antidepressants (β = -0.1308), or other antidepressants (β = -0.0637), compared with their counterparts in the selective serotonin reuptake inhibitors group (all P < 0.05). Compared with patients who were treated with selective serotonin reuptake inhibitors, those who were prescribed serotonin antagonists and reuptake inhibitors (β = -0.4934, P < 0.05) or tricyclic antidepressants (β = -0.4194, P < 0.05) had incurred lower costs pertaining to outpatient service, while considerably higher costs were borne by those patients embarked on the treatment of serotonin-norepinephrine reuptake inhibitors (β = 0.3228, P < 0.05) or other antidepressants (β = 0.1118, P < 0.05). We concluded that the initiation of various classes of antidepressants led to significant variations in health service utilization and costs among depressed patients.

ObjectivesThe total medical (economic) costs of haemodialysis (HD) and peritoneal dialysis (PD), including direct medical costs, out-of-pocket (OOP) costs and productivity losses, have become an important issue. This study aims to compare the direct non-medical costs and indirect medical costs of both modalities in Taiwan.Design and settingThis multicentre study included cross-sectional interviews of patients over 20 years old and articulate, who had been continuously receiving long-term HD or PD for more than 3 months between April 2015 and March 2016. Mann-Whitney U test, Wilcoxon rank-sum test and 1000 bootstrap procedures with replacement were used for analysis.Outcome measuresDifferences in OOP costs and productivity losses.ResultsThere were 308 HD and 246 PD patients available for analysis. HD patients had significantly higher monthly OOP costs than PD patients after bootstrap procedures (NTD 5912 vs NTD 5225, pConclusionsThe HD modality has higher OOP costs and productivity losses than the PD modality in Taiwan.

Objective: Although disease-related malnutrition has prognostic implications for patients with chronic obstructive pulmonary disease (COPD), its health-economic impact and clinical burdens are uncertain. We conducted a population-level study to investigate these questions. Methods: We excerpted data relevant to malnutrition, prolonged mechanical ventilation, and medications from claims by 1,197,098 patients which were consistent with COPD and registered by the Taiwan National Health Insurance Administration between 2009 and 2013. These patients were separated into cohorts with or without respiratory failure requiring long-term mechanical ventilation, and each cohort was divided to compare cases who developed malnutrition after their first diagnosis consistent with COPD, versus non-malnourished propensity-score matched controls. Results: The prevalence of malnutrition was 3.8% overall (10,259/287,000 non-ventilator-dependent; 1198/15,829 ventilator-dependent). Propensity-score matched non-ventilator-dependent patients who became malnourished (N = 10,242) had comparatively more hospitalizations, emergency room and outpatient visits, longer hospitalization (all p < 0.01), and higher mortality (HR =2.26, 95% CI 2.18‒2.34) than non-malnourished controls (N = 40,968). Malnourished ventilator-dependent patients, (N = 1,197) had higher rates of hospitalization, emergency room and outpatient visits, but shorter hospitalization (all p < .001) and lower mortality (HR =0.85, 95% CI 0.80‒0.93) than matched non-malnourished controls (N = 4,788). Total medical expenditure on malnourished non-ventilator-dependent COPD patients was 75% higher than controls (p < .001), whereas malnourished ventilator-dependent patients had total costs 7% lower than controls (p < .001). Conclusions: Malnourishment among COPD patients who were not dependent on mechanical ventilation was associated with greater healthcare resource utilization and higher aggregate medical costs.

Various studies have indicated that glucocorticoid supplementation during cardiopulmonary resuscitation (CPR), in conjunction with vasopressors, may improve outcomes in instances of cardiac arrest. However, further population-based analysis is warranted with respect to resuscitative and long-term survival benefits conferred by administering glucocorticoids in this setting.A total of 145,644 adult patients who experienced non-traumatic, cardiac arrest occurred at emergency room during years 2004-2011 were selected for study from the Taiwan National Health Insurance Research database. These patients were grouped as steroid and non-steroid recipients during CPR, and group members were matched in terms of patient characteristics, including presenting complaint, prior steroid use, resuscitative drugs and shocks delivered, treatment setting (medical center or not), socioeconomic status, and year that cardiac arrest occurred, through propensity scoring. Logistic regression analysis was performed to determine the impact of steroid usage on survival to admission, survival to discharge, and 1-year survival.Compared with matched non-steroid group members (n=8628), patients given steroid (n=2876) displayed significantly higher rates of survival to admission (38.32% vs 18.67%; adjusted OR=2.97, 95% CI 2.69-3.29; p0.0001), survival to discharge (14.50% vs 5.61%; adjusted OR=1.71, 95% CI 1.42-2.05; p0.0001), and 1-year overall survival (10.81% vs 4.74%; adjusted OR=1.48, 95% CI 1.22-1.79; p0.0001). Steroid use proved more beneficial in patients with COPD or asthma and in the absence of shockable rhythm during CPR.Glucocorticoid use during CPR is associated with improved survival-to-admission, survival-to-discharge, and 1-year survival rates.

Few studies on tumour necrosis factor (TNF) inhibitor-associated tuberculosis (TB) and hepatic events have been performed in regions where these risks are elevated. This study aimed to provide a direct comparison between adalimumab and etanercept in a high-risk population and to address the implications for physicians working with patients in such an environment.Data collected from the National Health Insurance Research Database (NHIRD) in Taiwan between 2007 and 2011 were analysed retrospectively for incidences of eight adverse events associated with TNF-α inhibitors. Hazard ratios (HRs) of adalimumab vs. etanercept were calculated using a Cox proportional hazards model.During this 5-year period, 86 events of TB were reported after 5317 person-years of exposure to adalimumab (1.62 events per 100 person-years), compared to 44 events after 7690 person-years of exposure to etanercept (0.57 events per 100 person-years). For serious hepatic events that led to hospitalization, 0.75 events were reported per 100 person-years of exposure to adalimumab compared to 0.39 events per 100 person-years of exposure to etanercept. Adjusted HRs for TB [aHR 3.06, 95% confidence interval (CI) 2.09-4.49, p 0.0001], hospitalization due to a hepatic event (aHR 2.05, 95% CI 1.27-3.30, p = 0.0035), and serious infection (aHR 1.48, 95% CI 1.19-1.84, p = 0.0005) attained significance.TNF-α-targeting therapies with the monoclonal antibody adalimumab confers significant added risk of TB and serious hepatic events compared to therapies with the soluble fusion protein etanercept. Tailored strategies to attenuate these risks are warranted in high-risk regions such as Taiwan.

Objective The aim of this study was to compare the treatment effectiveness between long-acting injectable risperidone and long-acting injectable first-generation antipsychotics among patients with bipolar disorder. Method We conducted a retrospective cohort study using Taiwan's National Health Insurance Research Database. Patients with bipolar disorder aged 15 years or higher, who were newly administered long-acting injectable antipsychotics between June 1, 2004 and December 31, 2011 were included. The clinical outcome indexes were hospitalization for any mood, manic/mixed, or depressive episodes. In addition, the all-cause discontinuation of long-acting injectable antipsychotic treatment was also assessed. Results A total of 3916 patients with bipolar disorder were extracted. Compared with risperidone, the use of first-generation antipsychotics was associated with a higher rate of hospitalization for any mood episode and major depressive episode. However, there was no statistically significant difference in treatment discontinuation rate between risperidone and first-generation antipsychotics. Limitations Information for the severity of mood symptoms, social support, life style, neurological and metabolic adverse effect was not available in this database. In addition, we only measured severe mood episodes with hospitalization as our outcome index. It may not be possible to generalize our findings to mild mood episodes. Conclusions Our findings suggested that patients treated with long-acting injectable risperidone might be superior to first-generation antipsychotics in the rate of psychiatric hospitalization.

OBJECTIVE To assess change in employment status in patients with bipolar disorder in comparison with non-mentally ill controls from 1 year before bipolar incidence to 10 years after. Sociodemographic factors of change in employment status were also examined for patients with bipolar disorder. METHOD A cohort of 502 patients with ICD-9-CM bipolar disorder was identified using claims data from the National Health Insurance Research Database of Taiwan between 1998 and 2001 and compared to non-mentally ill controls through December 31, 2008. The primary outcome measure was the time from bipolar incidence to the time of change in employment status, ie, from earning income to not earning income. RESULTS The probability of changing to a non-income earner was significantly higher (P < .0001) in patients with bipolar disorder than in controls over time, even before the incidence of bipolar disorder (27% vs 14% for patients with bipolar disorder vs controls, respectively). Risks of occupational deterioration in patients with bipolar disorder were greater in the year before incidence and in the following year, with gradually decreasing risks over the subsequent 2 years, and comparable to controls from the third year onward. The adjusted hazard ratio of changing to a non-income earner was 2.06 (95% CI, 1.82-2.33) in patients with bipolar disorder. Male sex, ages 18 to 25 years, lower payroll bracket (< NT$50,001 [US $1,489]), and living in an urban area and insured area in the Northern region were associated with the risk of changing to a non-income earner in patients with bipolar disorder. CONCLUSIONS Patients with bipolar disorder had poorer employment outcomes than the controls, with greater risks of occupational deterioration before and after the bipolar episodes. Employment status should be incorporated as a measure of functioning and of treatment and intervention effectiveness in clinical practices and research.

Background The aim of this study was to assess the association between various classes of antidepressants and the risk of medication noncompliance as well as suicidal behavior among depressed patients. Methods A retrospective cohort study was conducted utilizing two nationwide population-based datasets in Taiwan from 2010 to 2016. The outcome measures included the risk of medication noncompliance, attempted suicide, and completed suicide. Cox proportional hazards models with stratification of the propensity score deciles were performed. Results A total of 447,411 new antidepressant users were identified. Compared to SSRIs, patients who received SARIs [adjusted hazard ratio (aHR) = 1.124, 95% confidence interval (CI) = 1.108–1.142], SNRIs (aHR = 1.049, 95% CI = 1.033–1.065), and other classes of antidepressants (aHR = 1.037, 95% CI = 1.024–1.051) were more likely to exhibit poor medication noncompliance. Patients who received SNRIs had a higher risk of attempted suicide (aHR = 1.294, 95% CI = 1.114–1.513), compared to SSRIs. However, patents in the TCAs group revealed the opposite result (aHR = 0.543, 95% CI = 0.387–0.762). Concerning the risk of completed suicide, this analysis detected no statistical significance across different types of antidepressants. Limitations Although the universal coverage of Taiwan's national health insurance program tends to minimize the risk of selection and recall bias, it is difficult to rule out medical surveillance bias by using claim data. Conclusions This study demonstrated that classes of antidepressants exert different degrees of impact on the risk of medication noncompliance and attempted suicide, but not completed suicide, among depressed patients.

Pretreatment with statins is associated with improved outcomes in severe sepsis, acute coronary syndrome, and stroke. Patients with cardiac arrest experience sepsis-like syndrome and ischemia reperfusion injuries in the heart and brain. The objective of this study was to investigate the effects of statin use before cardiac arrest on outcomes in cardiac arrest patients. Medical records of 142,131 adult patients who experienced nontraumatic cardiac arrest and were resuscitated between 2004 and 2011 were analyzed. Patients were grouped into 2 groups: the "statin group" comprised patients who had received statin treatment for at least 30 days before the cardiac arrest event; the "never statin group" comprised patients who had no statin use within 30 days before the event. Patients with previous statin treatment had better chance of survival to hospital discharge (6.1% vs 4.3%, p0.0001) and 1-year survival (4.8% vs 3.2%, p0.0001) after propensity score matching. Previous statin use was an independent predictor for 1-year survival (adjusted odds ratio 1.41, 95% confidence interval 1.16 to 1.71; p = 0.001). A favorable outcome effect of statin on 1-year survival was observed in the presence of diabetes mellitus, chronic kidney disease, and Charlson Comorbidity Index score greater than 5 in the subgroup analysis. In conclusion, statin use before cardiac arrest is associated with 1-year survival in a propensity score-matched nationwide cohort study.

Aim To examine the changes in the risks of death and cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients treated with conventional synthetic or biologic disease-modifying antirheumatic drugs (csDMARD or bDMARD) during 1997-2013. Methods Two cohorts of RA patients and their matched controls were identified from the National Health Insurance Research database. There were 1569 patients in the csDMARD cohort who received cyclosporine ≥50 mg/d with concomitant usage of ≥2 csDMARDs during 1997-2003. There were 1530 patients in the bDMARD cohort if patients had ≥1 claim for bDMARD during 2003-2011. Adjusted hazard ratios (aHRs) for the risk of death, myocardial infarction, and stroke, were assessed using the Kaplan-Meier survival curves and the Cox proportional hazards models. Results Compared with matched cohorts, the incidence of death was higher with csDMARD with a more than 6-fold increase (csDMARD vs controls: 33% vs 5%); while it only increased with a much smaller magnitude with bDMARD (bDMARD vs controls: 15% vs 11%). In addition, an increase in the reduction of incidence rate of stroke with bDMARD (bDMARD vs controls: 2% vs 5%) than that with csDMARD (csDMARD vs controls: 3% vs 4%) was found. Results from multivariate analysis showed that RA patients receiving bDMARD had a significantly lower increase in the risk of deaths (aHR 1.05; 95% CI 0.84-1.33) compared with those receiving csDMARD (aHR 8.75; 95% CI 7.43-10.31). In addition, bDMARD was associated with a higher reduction in the risk of stroke compared with csDMARD (bDMARD: aHR 0.37; 95% CI 0.22-0.62; csDMARD: aHR 0.73; 95% CI 0.51-1.05). Conclusion Biologics used in RA patients have been shown to have a beneficial impact on improving clinical outcomes, including decreased risks of death and stroke. The economic burden from costs of biologics may be alleviated by improving outcomes.

Patients with end-stage renal disease (ESRD) on chronic hemodialysis (HD) experience chronic inflammation and immune dysregulation; whether these affect the development of chronic inflammatory disease such as psoriasis is unknown. We aimed to investigate the impact of ESRD on the development of psoriasis. We performed a retrospective cohort study using records between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Among 74 916 patients with ESRD on chronic HD and the control group comprising 74 916 sex and age group-matched patients, 165 and 81 incident psoriasis developed after a mean follow up of 2.4 and 2.9 years, respectively. The incidence rates of psoriasis in HD patients and the control group were 91.7 and 37.1 per 100 000 person-years, respectively (difference between groups, P < 0.001). HD patients had a shorter time to psoriasis diagnosis than the control group (P < 0.05). Cox proportional hazard adjustment showed the hazard ratio (HR) for psoriasis in HD patients as 2.09 (95% confidence interval [CI], 1.49-2.94; P < 0.001) than that of the control group. Younger HD patients had relatively higher risk of psoriatic development (age

The aim of the nationwide retrospective matched cohort study was to evaluate health service utilization and medical costs between patients with schizophrenia who received long-acting injectable (LAI) risperidone and those who took risperidone orally. Data were sourced from the 2008 to 2013 Psychiatric Inpatient Medical Claim Dataset in Taiwan. The sample selection process was performed by propensity score matching. Finally, there were 691 patients in the exposed cohort and 1382 patients in the unexposed cohort. Each patient was individually followed for a 1-year period. Two-part models and generalized estimating equations were used to evaluate health service utilization and direct medical costs of patients. Analytical results showed that patients receiving LAI risperidone had used outpatient services significantly more, had greater hospital admissions, and had shorter lengths of stay than those who took risperidone orally. Furthermore, compared with their counterparts in the unexposed group, patients in the exposed group had incurred higher medical costs because of costs incurred from increased utilization of outpatient service and hospital admissions, under the special context of the healthcare system in Taiwan, a single-payer universal health coverage system with low copayment rates. In summary, this study suggested that patients with schizophrenia treated with LAI risperidone had shorter lengths of stay, higher medical costs largely because of increased utilization of outpatient service and hospital admissions, compared with those who took risperidone orally.

Objective Adjuvant chemotherapy was introduced in patients with early-stage ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including taxane has not been established. Methods Patients with early-stage OC from the National Health Insurance Research database of Taiwan who received platinum plus cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3–6 cycles were recruited, and the disease-free survival (DFS) and overall survival (OS) were determined. Results A total of 1,510 early-stage OC patients, including 841 who received CP regimen and 699 who received PT regimen, were included. The 2 groups had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%; p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who received the CP regimen had a lower 5-year DFS than the patients ≤50 years of age who received the CP (p50 years of age who received the CP regimen had a worse 5-year OS compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age in the PT group; p=0.002 for patients ≤50 years of age in the CP group; and p=0.061 for patients ≤50 years of age in the PT group). Patients with the CP or PT regimen for 3–5 cycles had a similar 5-year DFS and OS compared to 6 cycles (p>0.050). Conclusion Chemotherapeutic regimens with taxane could be recommended for early-stage OC patients >50 years of age.

ObjectivesTo date, a value set for the EQ-5D-5L based on the health state preferences of the general Taiwanese population has not been available. This study aimed to develop a Taiwanese value set for EQ-5D-5L to facilitate health technology assessment for medical products and services.MethodsAn international standardized protocol for EQ-5D-5L valuation studies developed by the EuroQol group was adopted. Adult members of the general public were recruited from six geographic regions in Taiwan. In computer-based face-to-face interviews, each participant completed 10 composite time trade-off (C-TTO) tasks and 7 discrete choice experiment (DCE) tasks. The C-TTO and DCE data were modeled alone or in combination (using hybrid models) with additive models containing 20 dummy variables as main effects. The model performance was assessed both quantitatively and qualitatively (mainly logical consistency and prediction patterns).ResultsOf 1,073 recruited participants, 1,000 completed the study. Approximately 13% of observed utility values were -1 in the C-TTO tasks. The hybrid model, using all available data that assumed C-TTO response values left-censored at -1 and with main effects coefficients with logical consistency (monotonicity), was considered as the most appropriate model. The predicted utility ranged from -1.0259 to 1.ConclusionsAn EQ-5D-5L value set was developed for Taiwan using an established study protocol and a representative sample of the general population. This may facilitate health economic evaluations and decision making on resource allocation under Taiwan's national health insurance program in the future.

Patients with risk factors including younger age, mastoiditis, external ear disease, treatment by older surgeons, and concomitant mastoidectomy should receive detailed management to minimize the probability of re-operation for chronic otitis media (COM).Although COM remains a common ear disease requiring surgical intervention, its re-operation risks are less well-documented. This study aimed to compare patients with COM who underwent re-operation and those patients with no re-operation, and identify the risks of re-operation.This retrospective cohort study analyzed the trend of COM surgery from 1999-2009, and identified the re-operation risks of 18 895 patients with COM who underwent surgery from 2002-2006 using the National Health Insurance Research Database in Taiwan.Among the study population, 129 patients underwent revision surgery during a 5.5 ± 1.5 year follow-up period. A univariate logistic regression analysis showed that the re-operation rate was significantly higher in patients under 18 years of age, those with mastoiditis, disorders of external ear, treatment by surgeons of 50-64 years of age, use of a very high volume surgeon, and combined surgery with mastoidectomy. A multivariate analysis further limited the re-operation risk factors to younger patients, those with mastoiditis, external ear disorders, treatment by older surgeons, and concomitant mastoidectomy.

Summary Background An increased risk for ischaemic stroke has been reported in young hyperthyroidism patients independent of atrial fibrillation (AF). However, whether the use of antithyroid drugs in hyperthyroidism patients can reduce the occurrence of ischaemic stroke remains unclear. Methods A total of 36,510 newly diagnosed hyperthyroidism patients during 2003–2006 were identified from the Taiwan National Health Insurance Research database. Each patient was individually tracked for 5 years from their index date (beginning the antithyroid drugs) to identify those who suffered from new episode of ischaemic stroke. Medication possession ratio (MPR) was used to represent the antithyroid drug compliance. The association between the MPR and the risk of stroke was examined. Results The stroke incidence rates for hyperthyroidism patients with age

Objective To elicit a patient's willingness to participate in a diabetes pay-for-performance for patient (P4P4P) program using a discrete choice experiment method. Methods The survey was conducted in March 2013. Our sample was drawn from patients with diabetes at five hospitals in Taiwan ( International Classification of Diseases, Ninth Revision, Clinical Modification code 250). The sample size was 838 patients. The discrete choice experiment questionnaire included the attributes monthly cash rewards, exercise time, diet control, and program duration. We estimated a bivariate probit model to derive willingness-to-accept levels after accounting for the characteristics (e.g., severity and comorbidity) of patients with diabetes. Results The preferred program was a 3-year program involving 30 minutes of exercise per day and flexible diet control. Offering an incentive of approximately US $67 in cash per month appears to increase the likelihood that patients with diabetes will participate in the preferred P4P4P program by approximately 50%. Conclusions Patients with more disadvantageous characteristics (e.g., elderly, low income, greater comorbidity, and severity) could have less to gain from participating in the program and thus require a higher monetary incentive to compensate for the disutility caused by participating in the program's activities. Our result demonstrates that a modest financial incentive could increase the likelihood of program participation after accounting for the attributes of the P4P4P program and patients' characteristics.

In patients already receiving combination of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and calcium channel blocker (CCB), whether the choice of additional diuretic or beta-blocker affects the cardiovascular and cerebrovascular outcomes remains unclear. A total of 13,551 patients who were concurrently receiving three anti-hypertensive agents of different classes through outpatient clinics during 2004−2006 were identified from the National Health Insurance Research Database of Taiwan. Patients were further classified into two treatment groups according to the medication possession ratio of drug combinations; the A + B + C group as those who received concurrent therapy of ACEI/ARB, beta-blocker and CCB. The A + C + D group as patients who received ACEI/ARB, CCB, and diuretics. The event-free survival of stroke, acute myocardial infarction (AMI), mortality, and major adverse cardiovascular events (MACE) between the two treatment groups was investigated. After propensity score matching, there were 5120 patients in each group. There were no differences in the incidence of cardiovascular events between the two groups. In patients with prior history of cerebrovascular accident (CVA), the A + C + D group had a significantly higher AMI-free survival (adjusted HR = 1.56; 95% CI 1.051−2.307; p

Objective Whether migraine is associated with urinary calculi is an unresolved issue, although topiramate, a migraine-preventive agent, is known to contribute to this complication. This study investigates the association between migraine and the risk of urinary calculi. Methods We identified a total of 147,399 patients aged ≥18 years with migraine diagnoses recorded in the Taiwan National Health Insurance Research Database between 2005 and 2009. Each patient was randomly matched with one individual without headache using propensity scores. All participants were followed from the date of enrollment until urinary calculi development, death, or the end of 2010. Results The risk of urinary calculi was greater in the migraine than the control cohort (adjusted hazard ratio (aHR), 1.58; 95% confidence interval (CI), 1.52–1.63; p Conclusions Our study showed migraine was associated with an increased risk of urinary calculi, independent of topiramate use. A higher frequency of clinic visits was associated with a greater risk.