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Background Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. It has also imposed a substantial economic and social burden on the health care system. In Taiwan, a nationwide COPD pay-for-performance (P4P) program was designed to improve the quality of COPD-related care by introducing financial incentives for health care providers and employing a multidisciplinary team to deliver guideline-based, integrated care for patients with COPD, reducing adverse outcomes, especially COPD exacerbation. However, the results of a survey of the effectiveness of the pay-for-performance program in COPD management were inconclusive. To address this knowledge gap, this study evaluated the effectiveness of the COPD P4P program in Taiwan. Methods This retrospective cohort study used data from Taiwan’s National Health Insurance claims database and nationwide COPD P4P enrollment program records from June 2016 to December 2018. Patients with COPD were classified into P4P and non-P4P groups. Patients in the P4P group were matched at a ratio of 1:1 based on age, gender, region, accreditation level, Charlson Comorbidity Index (CCI), and inhaled medication prescription type to create the non-P4P group. A difference-in-difference analysis was used to evaluate the influence of the P4P program on the likelihood of COPD exacerbation, namely COPD-related emergency department (ED) visit, intensive care unit (ICU) admission, or hospitalization. Results The final sample of 14,288 patients comprised 7144 in each of the P4P and non-P4P groups. The prevalence of COPD-related ED visits, ICU admissions, and hospitalizations was higher in the P4P group than in the non-P4P group 1 year before enrollment. After enrollment, the P4P group exhibited a greater decrease in the prevalence of COPD-related ED visits and hospitalizations than the non-P4P group (ED visit: −2.98%, p, Graphical Abstract

Wen-Chien Cheng,1– 6 Biing-Ru Wu,1,3,5,6 Wei-Chih Liao,1,2,4,7 Chih-Yu Chen,1 Wei-Chun Chen,1,3– 6 Te-Chun Hsia,1,4,8 Chih-Yen Tu,1– 3 Chia-Hung Chen,1,2,7 Wu-Huei Hsu1 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 2School of Medicine, China Medical University, Taichung, Taiwan; 3Department of Life Science, National Chung Hsing University, Taichung, Taiwan; 4Department of Internal Medicine, Hyperbaric Oxygen Therapy Center, China Medical University Hospital, Taichung, Taiwan; 5Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 6Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan; 7Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; 8Department of Respiratory Therapy, China Medical University, Taichung, TaiwanCorrespondence: Chia-Hung Chen; Chih-Yu ChenDepartment of Internal Medicine, China Medical University Hospital, No. 2, Yude Road, Taichung, TaiwanEmail hsnu758@gmail.com; cychen0808@gmail.comPurpose: Triple therapy versus dual therapy for chronic pulmonary obstructive disease (COPD) can reduce symptoms, limit the risk of acute exacerbations (AEs) as well as improve lung function. Currently, studies that feature clinically important deterioration (CID) as a composite endpoint to assess the need for treatment intensification for patients maintained on dual therapy remained to be scarce.Patients and Methods: This study is a retrospective analysis (January 2014 to January 2018) of COPD patients that presented with moderate to severe AEs during the previous year with blood eosinophil counts ≥ 100 cells/μL. The first line of therapy included a combination of inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA). Composite CID was used in assessing the response to treatment after 24 weeks of therapy.Results: This study included 110 patients, of which 49 patients reportedly experienced CID. The most common events of CID include a decline in forced expiratory volume in 1 second (FEV1) ≥  100 mL from baseline (25/49, 51%) and an increase in COPD Assessment Test (CAT) scores ≥ 2 (13/49, 26.5%); many of these patients respond to the addition of a long-acting muscarinic antagonist (LAMA). Seven patients (7/110, 6.3%) experienced moderate to severe exacerbations while undergoing treatment with ICS/LABA. Univariate and multivariate analyses have identified low baseline FEV1 (OR = 0.81, p = 0.004), high CAT score (OR = 1.89, p = 0.004), and the frequency of AE (OR = 19.86, p = 0.021) as independent predictors of CID. A baseline FEV1 of ≤ 42%, an initial CAT score ≥ 18, and AE ≥ 2 last year were considered the optimal cut-off values, which were identified via receiver operating characteristics (ROC) curve analysis.Conclusion: Triple therapy (ICS/LABAs/LAMAs) may be considered as first-line treatment in patients experiencing more than 2 times moderate to severe AEs of COPD in the previous year and who have blood eosinophil counts ≥ 100 cells/μL, reduced lung function (FEV1 ≤ 42%), and more symptoms (CAT score ≥ 18).Keywords: inhaled corticosteroid, ICS, long-acting muscarinic antagonist, LAMA, long-acting β2 agonist, LABA, triple therapy, chronic pulmonary obstructive disease, COPD, clinically important deterioration, CID

Background Angiotensin receptor blockers (ARBs) have been reported to ameliorate anxiety and mood disorders in animal models. Cohort links between ARB use and suicide risk in humans require clarification. Methods Data were obtained from the National Health Insurance Research Database. Patients diagnosed as having hypertension according to the criteria of the International Classification of Diseases, Ninth Revision, Clinical Modification (401-405) from January 1, 2000 to December 31, 2012 were enrolled as the target population. We defined enrollees who had received ARB prescriptions for at least 28 days as ARB users. Those who had never taken ARB prior or during the study period were defined as ARB nonusers and were propensity score–matched with ARB users. The end outcome was confirmation of a suicide attempt. Results After propensity score matching was conducted, 40,976 ARB users and 40,976 nonusers were selected as the matched cohorts. The overall incidence rate of suicide attempt was significantly lower in ARB users than in nonusers (0.51 vs. 1.07 per 10,000 person-years; adjusted hazard ratio = 0.48, 95% confidence interval = 0.26–0.87). A Kaplan–Meier survival analysis with a log-rank test revealed a lower cumulative incidence of suicide attempt in ARB users than in nonusers (p Conclusions ARB use was not associated with an increased risk for suicide compared with non-ARB use.

Background We hypothesized that renin–angiotensin system (RAS) blockers have systemic protective effects beyond the respiratory tract and could reduce the risk of viral infections. Methods We used the National Health Insurance Research Database and identified 2 study cohorts: the angiotensin receptor blocker (ARB) cohort and angiotensin-converting enzyme inhibitor (ACEI) cohort. Propensity score matching was applied at a 1:1 ratio by all associated variables to select 2 independent control cohorts for the ARB and ACEI cohorts. A Cox proportional hazards model was applied to assess the end outcome of viral infection. Results The number of ARB and ACEI users was 20 207 and 18 029, respectively. The median age of ARB users and nonusers was 53.7 and 53.8 years, respectively. The median follow-up duration of ARB users and nonusers was 7.96 and 7.08 years; the median follow-up duration of ACEI users and nonusers was 8.70 and 8.98 years, respectively. The incidence rates of viral infections in ARB users and nonusers were 4.95 and 8.59 per 1000 person-years, respectively, and ARB users had a lower risk of viral infection than nonusers (adjusted hazard ratio [aHR], 0.53 [95% confidence interval {CI}, .48–.58]). The incidence rates of viral infections in ACEI users and nonusers were 6.10 per 1000 person-years and 7.72 per 1000 person-years, respectively, and ACEI users had a lower risk of viral infection than nonusers (aHR, 0.81 [95% CI, .74–.88]). Conclusions Hypertensive patients using either ARBs or ACEIs exhibit a lower risk of viral infection than nonusers.

Background We aimed to identify associations between the risk of acute respiratory failure (ARF) and types of antihypertensive agents in patients with viral pneumonia. Methods In this case-control study, data extracted from the Taiwan National Health Insurance Research Database were analysed. The base population comprised patients with viral pneumonia treated from 2000 to 2013. The case group comprised patients with ARF and the control group comprised participants without ARF. Adjusted odds ratios (ORs) were calculated using a multivariable logistic regression model. Results In total, 4427 viral pneumonia patients with ARF and 4427 matched control participants without ARF were recruited. Patients with diabetes, alcohol-related disease, asthma, chronic kidney disease or end-stage renal disease, chronic obstructive pulmonary disease, cancer, congestive heart failure, stroke, acute pulmonary oedema and shock had increased odds of developing ARF, especially shock (adjusted OR = 49.3; 95% CI = 27.4, 88.7), cancer (12.6; 8.67, 18.2) and stroke (7.51; 5.32, 10.6). Increasing odds of developing ARF were noted in patients using potassium-sparing diuretics (2.95; 1.54, 5.64), loop diuretics (68.2; 48.1, 96.6), calcium channel blockers (1.64; 1.26, 2.13) and angiotensin-converting enzyme inhibitors (1.70; 1.15, 2.53). Patients with prescriptions of α-blockers (0.44; 0.26, 0.74), β-blockers (0.37; 0.26, 0.52), thiazides (0.38; 0.25, 0.59) and angiotensin receptor blockers (0.65; 0.51, 0.83) had lower odds of having ARF. Conclusion Patients with viral pneumonia who received α-blockers, β-blockers, thiazides or angiotensin receptor blockers during hospitalisation had a lower risk of developing ARF.

Background: Air pollution is speculated to affect the reproductive health of women. However, a longitudinal association between exposure to air pollution and dysmenorrhea has not been identified, which this study aimed to examine this point.Methods: Two nationwide databases, namely the Taiwan Air Quality Monitoring database and the Taiwan National Health Research Institutes database were linked. Women with a history of dysmenorrhea (International Classification of Disease, Ninth Revision, Clinical Modification code 625.3) before 2000 were excluded. All participants were followed from January 1, 2000 until the diagnosis of dysmenorrhea, withdrawal from National Health Insurance, or December 31, 2013. Furthermore, air pollutants were categorized into quartiles with three cut-off points (25th, 50th, and 75th percentiles). The Cox regression model was used to calculate the hazard ratios of dysmenorrhea.Results: This study enrolled 296,078 women. The mean concentrations of yearly air pollutants were 28.2 (±12.6) ppb for nitric oxides (NOx), 8.91 (±7.93) ppb for nitric oxide (NO), 19.3 (±5.49) ppb for nitrogen dioxide (NO2), 0.54 (±0.18) ppm for carbon monoxide (CO), and 31.8 (±6.80) μg/m3 for PM2.5. In total, 12,514 individuals developed dysmenorrhea during the 12-year follow-up. Relative to women exposed to Q1 concentrations of NOx, women exposed to Q4 concentrations exhibited a significantly higher dysmenorrhea risk [adjusted hazard ratio (aHR)= 27.9, 95% confidence interval (CI) = 21.6–31.3]; similarly higher risk was found for exposure to NO (aHR = 16.7, 95% CI = 15.4–18.4) and NO2 (aHR = 33.1, 95% CI = 30.9–37.4). For CO, the relative dysmenorrhea risk in women with Q4 level exposure was 28.7 (95% CI = 25.4–33.6). For PM2.5, women at the Q4 exposure level were 27.6 times (95% CI = 23.1–29.1) more likely to develop dysmenorrhea than those at the Q1 exposure level.Conclusion: Our results showed that women would have higher dysmenorrhea incidences while exposure to high concentrations of NO, NO2, NOx, CO, and PM2.5.

BACKGROUND: According to several phase III studies, tiotropium [a long-acting muscarinic antagonist (LAMA)] is a well-tolerated add-on therapy to inhaled corticosteroids (ICS) for asthmatics with or without the addition of long-acting beta2-agonists (LABAs). However, real-world studies based on clinical phenotypes to predict the long-term need of tiotropium as an add-on therapy for asthmatics are limited. METHODS: This is a retrospective study conducted at a single medical center in Taiwan from July 2016 to July 2018. An asthma control test (ACT) is applied to uncontrolled asthmatics to evaluate the effectiveness of tiotropium as an add-on therapy. Asthmatic subgroups with different clinical phenotypes and needing long-term tiotropium as a maintenance treatment are identified. The effectiveness of tiotropium add-on therapy is defined as an improvement of ACT score ≥3 points 3 months after the treatment (vs. baseline), while the long-term requirement of tiotropium is defined as tiotropium dependency >1 year. RESULTS: The study analyzed a total of 160 uncontrolled asthmatics regardless of low- or medium-to-high-dose ICS plus LABA. One hundred and twelve patients responded well (ACT score increased ≥3 points) to tiotropium. These patients were further divided into two subgroups: one with tiotropium add-on therapy for ≥1 year due to patients’ difficulties in stepping down from tiotropium; the other with tiotropium add-on therapy for 30 kg/m(2) were predictors for asthmatics requiring long-term tiotropium add-on therapy. CONCLUSIONS: Tiotropium add-on therapy is effective for uncontrolled asthmatics. Moreover, patients with ACO, initial FEV1% predicted 30 kg/m(2) require long-term tiotropium add-on therapy for asthma control.

Background: Patients with chronic kidney disease (CKD) receiving maintenance renal replacement therapy are at higher risk of tuberculosis (TB) infection. The risk of TB infection in CKD patients not receiving dialysis is unknown.Aim: We conduct this study to test the hypothesis that TB infection is negatively correlated to renal function.Design: Non-dialysis CKD stage 1–5 patients, admitted in China Medical University Hospital from January of 2003 to May of 2014, were enrolled in this study and were prospectively followed up to the diagnosis of TB, death, loss to follow-up, or December 2014. The risk factors of TB infection were analyzed using competing-risks regression analysis with time-varying covariates. The initiation of dialysis and patients' death were considered as competing events. Patients' estimated glomerular filtration rate (eGFR) and body mass index (BMI) were recorded at enrollment.Results: They were followed-up for a median duration of 1.4 years. Of the 7221 patients, TB infection was identified in 114 patients. Higher eGFR was associated with lower risk of TB infection (P < 0.01). The adjusted subdistribution hazard ratio (aSHR) was 0.82 [95% confidence interval (CI), 0.72 to 0.94] for every 5 ml/min/1.73 m2 increase in eGFR. In addition, higher BMI (p = 0.01) was associated with a lower risk of TB infection and the aSHR was 0.91 (95% CI, 0.85 to 0.98) for every 1 kg/m2 increase in BMI.Conclusion: Renal function and body mass index are independently associated with the risk of tuberculosis infection in patients with chronic kidney disease not receiving dialysis.

The evidence indicates that the optimal observation period following renal biopsy ranges between 6 and 8 h. This systematic review and meta-analysis explored whether differences exist in the complication rates of renal biopsies performed in outpatient and inpatient settings. Methods: We searched the MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 1985 to February 2020. Two reviewers independently selected studies evaluating the bleeding risk from renal biopsies performed in outpatient and inpatient settings and reviewed their full texts. The primary and secondary outcomes were risks of bleeding and major events (including mortality) following the procedure, respectively. Subgroup analysis was conducted according to the original study design (i.e., prospective or retrospective). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effect meta-analysis. Heterogeneity was assessed using the I2 test. Results:Data from all 10 eligible studies, which included a total of 1801 patients and 203 bleeding events, were included for analysis. Renal biopsies in outpatient settings were not associated with a higher bleeding risk than those in inpatient settings (OR = 0.81, 95% CI, 0.59–1.11, I2 = 0%). The risk of major events was also comparable across both groups (OR = 0.45, 95% CI, 0.16–1.29, I2 = 4 %). Conclusions:Similar rates of bleeding and major events following renal biopsy in outpatient and inpatient settings were observed.

Chronic obstructive pulmonary disease (COPD) is preventable and treatable. However, many patients remain undiagnosed and untreated due to the underutilization or unavailability of spirometers. Accordingly, we used Spirobank Smart, an app-based spirometer, for facilitating the early detection of COPD in outpatient clinics. This prospective study recruited individuals who were at risk of COPD (i.e., with age of ≥40 years, ≥10 pack-years of smoking, and at least one respiratory symptoms) but had no previous COPD diagnosis. Eligible participants were examined with Spirobank Smart and then underwent confirmatory spirometry (performed using a diagnostic spirometer), regardless of their Spirobank Smart test results. COPD was defined and confirmed using the postbronchodilator forced expiratory volume in 1 s/forced vital capacity values of &lt, 0.70 as measured by confirmatory spirometry. A total of 767 participants were enrolled and examined using Spirobank Smart, 370 participants (94.3% men, mean age of 60.9 years and mean 42.6 pack-years of smoking) underwent confirmatory spirometry. Confirmatory spirometry identified COPD in 103 participants (27.8%). At the optimal cutoff point of 0.74 that was determined using Spirobank Smart for COPD diagnosis, the area under the receiver operating characteristic was 0.903 (95% confidence interval (CI) = 0.860–0.947). Multivariate logistic regression revealed that participants who have an FEV1/FVC ratio of &lt, 74% that was determined using Spirobank Smart (odds ratio (OR) = 58.58, 95% CI = 27.29–125.75) and old age (OR = 3.23, 95% CI = 1.04–10.07 for 60 ≤ age &lt, 65, OR = 5.82, 95% CI = 2.22–15.27 for age ≥ 65) had a higher risk of COPD. The Spirobank Smart is a simple and adequate tool for early COPD detection in outpatient clinics. Early diagnosis and appropriate therapy based on GOLD guidelines can positively influence respiratory symptoms and quality of life.

Background Few large-scale cohort studies have investigated the association between community acquired pneumonia and the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). We aimed to study whether using ACEIs or ARBs had protective effects for community acquired pneumonia. Methods This database cohort study was conducted retrospectively in Taiwan. The hypertensive patients were the target population of this study. Patients with ARB use were defined as our first study cohort. The second study cohort comprised patients who used ACEI. Propensity-score matching at 1:1 was used between ARB users and non-ARB users. We recruited 67 944 participants for the ARB study and 58 062 participants for the ACEI study. The same matching was also performed between ACEI users and non-ACEI users. Cox proportional hazard regression was used to analyze the risk of the outcome of viral pneumonia. Results The hazard ratio of community acquired pneumonia for ARB users relative to non-ARB users was 0.33. The hazard ratio of community acquired pneumonia was 0.71 times in ACEI users compared with ACEI nonusers. In stratification analysis, both ARB and ACEI both exhibited a protective effect for community acquired pneumonia in each age and sex group. In the analysis of the effects of therapy duration, patients using ARB for fewer than 100 days exhibited a greater reduction in the risk of community acquired pneumonia (adjusted HR = 0.58) compared with the non-ARB cohort. For the ACEI study, patients who used ACEI for 121 to 450 days were more likely to exhibit reduced risks of community acquired pneumonia (adjusted HR = 0.5). Conclusion Both ACEI and ARB uses were associated with decreased risk of community acquired pneumonia infection.

Objectives We aimed to investigate whether the risk of diabetes mellitus (DM) is heightened in patients with prostate cancer receiving injection therapy. Methods Men diagnosed with prostate cancer between 2000 and 2012 were included in the case cohort, and men without prostate cancer were included as controls. Each patient with prostate cancer was matched with a control patient with the same index year, demographic variables and comorbidities, and comparisons were made using propensity score matching. The hazard ratio of DM was estimated using the Cox proportional hazards model. Results This cohort study consisted of 1213 patients with prostate cancer and 1213 control patients. The risk of DM in patients with prostate cancer was 1.60 times (95% CI = 1.12, 2.27) that of patients without prostate cancer. Compared with the controls, the hazard ratios of DM for patients with prostate cancer not receiving oral hormone therapy, patients with prostate cancer receiving oral hormone therapy, and patients with prostate cancer not receiving injection hormone therapy were 1.65 (95% CI = 1.01, 2.70), 1.57 (95% CI = 1.07, 2.70), and 1.94 (95% CI = 1.34, 2.81), respectively. The risk of DM in patients who received injection hormone therapy was 0.45 times (95% CI = 0.25, 0.82) that of patients who did not receive injection hormone therapy. Conclusion Patients with prostate cancer had an increased risk of DM compared with patients without prostate cancer. Patients with prostate cancer who received injection therapy had a lower risk of DM compared with those who did not.

BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

Background Whether patients with end-stage renal disease (ESRD) have a higher risk of idiopathic polyneuropathy (IPN) than those without ESRD remains unclear. We hypothesised that carpal tunnel syndrome (CTS) is a prodrome of IPN in patients with ESRD. Methods Data were collected from the Taiwan National Health Insurance research database (NHIRD) for the 2000-2011 period. Two matching strategies, age- and sex-matching and propensity matching, were used, which yielded 2596 age- and sex-matched patients with ESRD and 2210 propensity-matched patients with ESRD. The comparison cohort was chosen in a 1:4 ratio for the age- and sex-matched method and in a 1:1 ratio for the propensity-matching method. The primary outcome was the incidence of IPN. Cox proportional hazards modelling was used. Results In the age- and sex-matched cohort, the IPN incidence was 7.64 and 2.88 per 1000 person-years for the ESRD and controls cohorts, respectively. After we adjusted for age, sex, comorbidities and medications relative to controls, having ESRD was significantly associated with increased risk of IPN (hazard ratio [HR] = 2.45, 95% confidence interval [CI] = 1.76-3.41). Competing risk of death as sensitivity analysis revealed that having ESRD with CTS was still associated with higher risk of IPN than having CTS without ESRD (HR = 2.85, 95% CI = 1.87-4.34). Conclusion Patients with ESRD with CTS had higher incidences of idiopathic peripheral neuropathy than those without ESRD with CTS.

Background: Direct evidence of lung cancer risk in Asian users of angiotensin-converting enzyme inhibitors (ACEIs) is lacking. Methods: The ACEI cohort comprised 22,384 patients aged &ge, 18 years with a first prescription of ACEI. The comparison angiotensin receptor blocker (ARB) cohort consisted of age-, sex- and comorbidity-matched patients at a ratio of 1:1. The primary outcome was the incidence of lung cancer, which was evaluated using a proportional hazard model. Results: The overall incidence rates of lung cancer in the ACEI and ARB cohorts were 16.6 and 12.2 per 10,000 person-years, respectively. The ACEI cohort had a significantly higher risk of lung cancer than the ARB cohort (adjusted hazard ratio [aHR]. = 1.36, 95% confidence interval [CI]. = 1.11&ndash, 1.67). Duration&ndash, response and dose&ndash, response analyses revealed that compared with patients who did not receive ACEIs, patients who received ACEIs for more than 45 days per year (aHR = 1.87, 95% CI = 1.48&ndash, 2.36) and patients who received more than 540 defined daily doses of ACEIs per year (aHR =1.80, 95% CI = 1.43&ndash, 2.27) had a significantly higher risk of lung cancer. The cumulative incidence of lung cancer was also significantly higher in the ACEI cohort than in the ARB cohort (log-rank test, p = 0.002). Conclusions: ACEI use is associated with an increased risk of lung cancer compared with ARB use. Patients using ARBs have a significantly lower risk of lung cancer than non-ARB users.

Background: The objective of this study was aimed to investigate whether sleep apnea patients had a higher risk of traumatic brain injury. Methods: Data were collected from the Taiwan Longitudinal Health Insurance Database during the period of 2000–2012. The study cohort comprised 6,456 patients aged ≥20 years with a first diagnosis of sleep apnea. The primary outcome was the incidence of traumatic brain injury. Kaplan-Meier survival analysis and Cox proportional-hazards modeling were used. Results: After adjustments for associated comorbidities and hypnotic medications, sleep apnea patients were associated with a 1.19-fold higher risk of traumatic brain injury (95% CI, 1.07–1.33) compared with patients without sleep apnea. Sleep apnea patients who took benzodiazepine (BZD) had a 1.30-fold increased risk of traumatic brain injury compared with patients without sleep apnea (95% CI, 1.14–1.49). However, this risk was not statistically significant, with a 1.03-fold risk of traumatic brain injury in sleep apnea patients without BZD use (95% CI, 0.84–1.25) compared with patients without sleep apnea. Compared with patients without sleep apnea, the risk of traumatic brain injury in sleep apnea patients aged 65–79 years old was higher (adjusted hazard ratio, 1.36; 95% CI, 1.06–1.74). Conclusion: Sleep apnea patients, regardless of hypnotic use, had a higher risk of traumatic brain injury compared with patients without sleep apnea.

Background: Association between hydroxychloroquine (HCQ) and bacterial infections required to be determined. Whether hydroxychloroquinehad use could reduce lesser risk of bacterial infections are unknown. We aimed to conduct a retrospective cohort propensity-matching study to investigate the association between HCQ use and the incidence of bacterial pneumonia in rheumatic patients. Methods: The Longitudinal Health Insurance Database (LHID), a one million extract from Taiwan National Health Insurance Research Database (NHIRD) of 23 million Taiwanese populations was used. We included patients who newly diagnosed rheumatic and immune disease (ICD-9-CM codes 696.0, 710, 714) within 2000-2012.HCQ users and nonusers were then matched according to age, sex, urbanization level, monthly income, comorbidities and medications in the ratio of 1:1 by the propensity score matching. Cox proportional hazard model was used to evaluate the risk of bacterial pneumonia in rheumatic patients who used HCQ and who did not use HCQ. Results: There were total 3285 patients with rheumatic and immune disease enrolled. The cumulative incidence curve of patients with the use of HCQ sulfate had no difference to that of patient without the use of HCQ sulfate in propensity score matched cohort, (Log-rank test: p-value=0.5). However, patients used HCQ sulfate for more than 1400 average use days had a lesser risk of bacterial pneumonia (adjusted HR=0.55, 95% CI=0.35, 0.89) in the cohort matched, with regarding HCQ nonusers as a reference. Conclusion: Rheumatic patients taking HCQ had no overall significant differences of bacterial pneumonia incidences compared with rheumatic patients not taking HCQ. HCQ used more than >1400 days was associated with lower risk of bacteria pneumonia. Funding Statement: This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW109-TDU-B-212-114004), China Medical University Hospital (CMU107-ASIA-19, DMR-109-231); MOST Clinical Trial Consortium for Stroke (MOST 108-2321-B-039-003-), Tseng-Lien Lin Foundation, Taichung, Taiwan. No additional external funding was received for this study. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the Institutional Review Board of the China Medical University Hospital (CMUH104-REC2-115(AR-4)).

Background: Long-acting muscarinic antagonist (LAMA) tiotropium improved lung function and reduced risks of exacerbation when added on to inhaled corticosteroids (ICS) with or without long-acting B2 agonists (LABAs) in patients with uncontrolled asthma. However, studies predicting the effectiveness of tiotropium based on patients’ clinical characteristics were limited. Methods: We conducted this retrospective study at a single medical center from July 2016 to July 2017, and used asthma control test (ACT) to evaluate the effectiveness of tiotropium add-on therapy in patients with uncontrolled asthma. The effectiveness was shown by an increase in ACT score from baseline of 3 or greater after 3 months of tiotropium add-on therapy. Results: Patients with uncontrolled asthma despite the use of low- or medium- to high-dose of ICS plus LABA (n=160) were analyzed. Among patients having good response (n=112, ACT score increased ≥3 points) to tiotropium (TGR group) and patients having poor response (n=48, ACT increased 30 were predictors of the effectiveness of tiotropium. Patients with high serum total IgE level >430 µg/L and eosinophil count >0.6×10 9 /L had a negative impact on response to tiotropium. Multivariate logistic regression analysis demonstrated that the independent factor of poor response to tiotropium was high serum IgE level >430 µg/L. Conclusions: Tiotropium add-on therapy in patients with uncontrolled asthma was effective. However, patients with serum total IgE level >430 µg/L were less likely to benefit from tiotropium.

// Jun-Jun Yeh 1, 2, 3, 4, * , Yu-Feng Wei 5 , Cheng-Li Lin 6, 7 and Wu-Huei Hsu 8, 9, * 1 Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan 2 Chia Nan University of Pharmacy and Science, Tainan, Taiwan 3 Meiho University, Pingtung, Taiwan 4 Pingtung Christian Hospital, Pingtung, Taiwan 5 Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan 6 Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan 7 College of Medicine, China Medical University, Taichung, Taiwan 8 Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan 9 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan * These authors contributed equally to this work Correspondence to: Wu-Huei Hsu, email: pccm.hsu@gmail.com Jun-Jun Yeh, email: anvin.funlan@msa.hinet.net Keywords: asthma–chronic obstructive pulmonary disease syndrome (ACOS); stroke; Parkinson's disease (PD); dementia; inhaler steroids Received: April 25, 2017 Accepted: November 10, 2017 Published: December 26, 2017 ABSTRACT Background: To evaluate the association of asthma–chronic obstructive pulmonary disease syndrome (ACOS) with neurodegenerative diseases (stroke, Parkinson's disease and dementia) and the role of the steroids in the neurodegenerative diseases among the ACOS cohort. Materials and Methods: Comparison of the ACOS cohort ( N = 10,260) with the non-ACOS cohort ( n = 20,513) based on the patients aged ≧40 years in the National Health Insurance Research Database from January 1, 2000 to December 31, 2010. These patients follow up to diagnosis of neurodegenerative diseases or the December 31, 2011; using multivariable Cox proportional hazards models. Results: After adjustment for potential confounders, the [adjusted hazard ratio (aHR), 95% confidence interval (CI)] in the ACOS cohort were [1.39, 1.28–1.50] [1.56, 1.34–1.81] and [1.43, 1.29–1.59] for stroke, Parkinson's disease, dementia; respectively. The [aHR, 95% CI] for ACOS cohort with (inhaler corticosteroids ≧0.13 gram/ oral steroids ≧0.08gram) were with less risk (all aHR 0.43 gram. The risk of stroke and dementia were the lower in patients with < 250 μg/d of a fluticasone equivalent inhaler corticosteroids (aHR = 0.53, 95% CI = 0.35–0.79; aHR = 0.53, 95% CI = 0.31–0.90, respectively). Conclusions: The ACOS cohort had a higher risk of the neurodegenerative diseases. The lower dose of the inhaler corticosteroids with cumulative dose ≧0.13 gram have the less risk of stroke and dementia.

Background: Studies have reported an association between asthma and oral diseases, including periodontal diseases. The aim of this retrospective study is to investigate risk of periodontal diseases for patients with asthma.Methods: Using the claims data of National Health Insurance of Taiwan and patients without a history of periodontal diseases, 19,206 asthmatic patients, who were newly diagnosed from 2000 through 2010, were identified. For each case, four comparison individuals without history of asthma and periodontal disease were randomly selected from the general population and frequency matched (categorical matched) by sex, age, and year of diagnosis (n = 76,824). Both cohorts were followed to the end of 2011 to monitor occurrence of periodontal diseases. Adjusted hazard ratios (aHRs) of periodontal disease were estimated using Cox proportional hazards regression analysis.Results: Overall incidence of periodontal diseases was 1.18-fold greater in the asthma cohort than in the comparison cohort (P

Pleural empyema is an important complication of pneumonia. Patients with stroke are at a higher risk developing pneumonia; however, the association between stroke and pleural empyema risk is largely unknown. We used the data from the National Health Insurance Research Database of Taiwan to establish a stroke group consisting of 466,170 patients diagnosed between 2000 and 2010, and a non-stroke group consisting of the same number of individuals matched by the propensity score. Incident pleural empyema was monitored toward the end of 2011. Adjusted hazard ratios (aHRs) of pleural empyema in the stroke group, compared to the non-stroke group, were estimated using the Cox proportional hazards model. We found that the incidence of pleural empyema is 2.69-fold higher in the stroke group than in the non-stroke group (15.2 vs. 5.59/10,000 person-years, p

Backgrounds Worldwide, the incidence of acute kidney injury (AKI) has been increasing. However, information on the long-term incidence of Parkinson disease (PD) in patients with AKI has not been reported. Methods A total of 9380 patients with AKI and 37,484 age- and sex-matched patients who did not have AKI were identified during 2003–2011. All patients were tracked until a diagnosis of PD, death, or the end of 2011. Cumulative incidences and hazard ratios (HRs) were calculated. Results The mean follow-up time for PD was 6.89 (SD = 3.30) years in the AKI cohort and 6.78 (SD = 3.29) years in the non-AKI cohort. The overall incidence densities of PD were significantly higher in the AKI cohort than in the non-AKI cohort (6.04 vs. 3.99/1000 person-years), with an adjusted HR of 1.47 (95% confidence interval [CI] = 1.18–1.83). Compared with the patients in the non-AKI cohort aged ≤ 64 years, the relative risk (95% CI) of PD was 2.17 (1.12–4.18), 14.1 (9.16–21.8), and 14.1 (8.43–23.6) for the patients in the AKI cohort aged ≤ 64, 65–79, and ≥ 80 years, respectively. Conclusion Patients with AKI were associated with a higher long-term risk of PD.

Background: Air pollutants cause endocrine disorders and hormone disruption. The relationship between air pollutants and polycystic ovary syndrome (PCOS) must be carefully investigated using a nationwide cohort. Methods: Data were extracted from two nationwide databases, namely Longitudinal Health Insurance Database and Taiwan Air Quality Monitoring Database, and analyzed. The study considered a range of data that began on 1 January 2000 and ended on 31 December 2013. Women diagnosed with PCOS were excluded. From the residential data, the study assessed the daily concentrations of sulfur dioxide (SO2), nitrogen oxides (NOx), nitrogen monoxide (NO), nitrogen dioxide (NO2), and PM2.5 the women were exposed to. A Cox proportional hazard regression model was applied to assess PCOS risk. Results: In total, 91,803 women were enrolled in this study, of those women, 2072 developed PCOS after 12 years of follow-up. The mean daily concentrations of SO2, NOx, NO, NO2, and PM2.5 women were exposed to were 4.25 (&plusmn, 1.44) ppb, 20.41 (&plusmn, 6.65) ppb, 9.25 (&plusmn, 4.36) ppb, 20.99 (&plusmn, 3.33) ppb, and 30.85 (&plusmn, 6.16) &mu, g/m3, respectively. Compared with the first-quartile levels of exposure, the fourth-quartile levels of exposure to SO2, NOx, NO, NO2, and PM2.5 increased PCOS risk by 10.31 times (95% CI = 8.35&ndash, 12.7), 3.37 times (95% CI = 2.86&ndash, 3.96), 4.18 times (95% CI = 3.57&ndash, 4.89), 7.46 times (95% CI = 6.38&ndash, 8.71), and 3.56 times (95% CI = 3.05&ndash, 4.15), respectively. Conclusion: Women exposed to a high concentrations of air pollutants, namely SO2, NO, NO2, NOx, and PM2.5, had a high PCOS risk.

Air pollutants have been reported to be a possible risk factor of chronic kidney disease (CKD). However, epidemiologic results regarding acidic gases and CKD have yet to be elucidated. We linked the Taiwan Air Quality Monitoring Database (TAQMD) to the Longitudinal Health Insurance Database. An observational cohort of 161,970 Taiwan citizens who had not been diagnosed with CKD was formed. The concentrations of air pollutant were classified into four levels based on quartile. Multivariable and univariable Cox proportional hazard regression models were used to assess the risk of developing CKD and end-stage renal disease (ESRD). Compared with Q1-level SO2, exposure to the Q4 level was at a 1.46-fold risk of developing CKD (95% confidence interval [CI] = 1.28-1.65) and 1.32-fold risk of ESRD (95% CI = 1.03-1.70). Compared with Q1-level NOx, exposure to the Q4 level was at a 1.39-fold higher risk of developing CKD (95% CI = 1.22-1.58) and 1.70-fold risk of ESRD (95% CI = 1.33-2.18). Compared with Q1-level NO, exposure to the Q4 level was at a 1.48-fold risk of CKD (95% CI = 1.30-1.68) and 1.54-fold risk of ESRD (95% CI = 1.20-1.98). Compared with Q1-level particles2.5 μm (PM2.5), exposure to the Q4 level were at a 1.74-fold risk of CKD (95% CI = 1.53-1.98) and 1.69-fold risk of ESRD (95% CI = 1.32-2.16). Exposure to particulate and acidic gas air pollution was observed to be associated with an increased risk of CKD and ESRD.

Purpose: The association between neurodegenerative diseases and transfusion remains to be investigated. Methods: The study population comprised 63,813 patients who underwent a blood transfusion and 63,813 propensity score-matched controls between 2000 and 2010. Data were obtained from the Taiwan National Health Insurance Research Database, which is maintained by the National Health Research Institutes. A Cox regression analysis was conducted to elucidate the relationship between blood transfusions and the risk of dementia. Results: A multivariate Cox regression analysis of factors, such as age, sex, cardiovascular ischemia disease, and depression, revealed that patients who underwent a blood transfusion showed a 1.73-fold higher risk of dementia [95% confidence interval (CI) = 1.62-1.84] and a 1.37-fold higher risk of Alzheimer’s disease (AD) [95% CI = 1.13-1.66] than those who did not. Patients who received a transfusion of washed red blood cells showed a 2.37-fold higher risk of dementia (95% CI = 1.63-3.44) than those who did not. Conclusion: Blood transfusion, especially transfusion of any type of red blood cells is associated with an increased risk of dementia.

Background: Prognosis of the aged population requiring maintenance dialysis has been reportedly poor. We aimed to develop prediction models for one-year cost and one-year mortality in aged individuals requiring dialysis to assist decision-making for deciding whether aged people should receive dialysis or not. Methods: We used data from the National Health Insurance Research Database (NHIRD). We identified patients first enrolled in the NHIRD from 2000&ndash, 2011 for end-stage renal disease (ESRD) who underwent regular dialysis. A total of 48,153 Patients with ESRD aged &ge, 65 years with complete age and sex information were included in the ESRD cohort. The total medical cost per patient (measured in US dollars) within one year after ESRD diagnosis was our study&rsquo, s main outcome variable. We were also concerned with mortality as another outcome. In this study, we compared the performance of the random forest prediction model and of the artificial neural network prediction model for predicting patient cost and mortality. Results: In the cost regression model, the random forest model outperforms the artificial neural network according to the mean squared error and mean absolute error. In the mortality classification model, the receiver operating characteristic (ROC) curves of both models were significantly better than the null hypothesis area of 0.5, and random forest model outperformed the artificial neural network. Random forest model outperforms the artificial neural network models achieved similar performance in the test set across all data. Conclusions: Applying artificial intelligence modeling could help to provide reliable information about one-year outcomes following dialysis in the aged and super-aged populations, those with cancer, alcohol-related disease, stroke, chronic obstructive pulmonary disease (COPD), previous hip fracture, osteoporosis, dementia, and previous respiratory failure had higher medical costs and a high mortality rate.

Aims This study investigated whether patients with alcoholic cirrhosis have a high risk of hemorrhagic stroke. Methods In this study, 17,094 patients diagnosed with cirrhosis between 2000 and 2010 were identified using the Taiwan National Health Insurance claims data. Identified patients were randomly selected and propensity score matched with individuals without cirrhosis according to age, sex, comorbidities and index year. Results The overall incidence rate of stroke was 4.41 and 12.1 per 1000 person-years in the chronic liver disease and cirrhosis (CLDC) with hepatitis B virus (HBV) or hepatitis C virus (HCV) cohort and the alcoholic CLDC cohort, respectively. The alcoholic CLDC cohort exhibited a 4.53-fold higher risk of hemorrhagic stroke (adjusted subhazard ratio [aSHR] = 4.53, 95% confidence interval [CI] = 3.05-6.71) than did the non-CLDC cohort, and the CLDC with HBV or HCV cohort exhibited a 1.40-fold higher risk of hemorrhagic stroke (aSHR = 1.40, 95% CI = 1.10-1.78) than did the non-CLDC cohort. The alcoholic CLDC cohort and the CLDC with HBV or HCV cohort showed an aSHR of 1.80 (95% CI = 1.36-2.40) and 0.95 (95% CI = 0.83-1.07) for ischemic stroke, respectively, compared with the non-CLDC cohort. Conclusion Alcoholic patients with CLDC had a higher risk of hemorrhagic stroke compared with non-alcoholic patients with CLDC and patients without CLDC.

Background: Air pollution has been associated with autoimmune diseases. Nephrotic syndrome is a clinical manifestation of immune-mediated glomerulopathy. However, the association between nephrotic syndrome and air pollution constituents remains unknown. We conducted this nationwide retrospective study to investigate the association between PM2.5 and nephrotic syndrome. Methods: We used the Longitudinal Health Insurance Database (LHID) and the Taiwan Air Quality-Monitoring Database (TAQMD). We combined and stratified the LHID and the TAQMD data by residential areas of insurants linked to nearby air quality-monitoring stations. Air pollutant concentrations were grouped into four levels based on quartile. Univariable and multivariable Cox proportional hazard regression models were applied. Findings: Relative to Q1-level SO2, subjects exposed to the Q4 level were associated with a 2.00-fold higher risk of nephrotic syndrome (adjusted HR = 2.00, 95% CI = 1.66&ndash, 2.41). In NOx, relative to Q1 NOx concentrations, the adjusted HRs of nephrotic syndrome risk were 1.53 (95% CI = 1.23&ndash, 1.91), 1.30 (95% CI = 1.03&ndash, 1.65), and 2.08 (95% CI = 1.69&ndash, 2.56) for Q2, Q3, and Q4 levels, respectively. The results revealed an increasing trend for nephrotic syndrome risk correlating with increasing levels of NO, NO2, and PM2.5 concentrations. Interpretation: High concentrations of PM2.5, NO, NO2, and SO2 are associated with increased risk of nephrotic syndrome.

The objective of this nationwide cohort study was to investigate the risk of peptic ulcer disease (PUD) in living liver donors (LDs). A total of 1333 LDs and 5332 matched nondonors were identified during 2003-2011. Hospitalized patients identified as LDs were assigned to the LD cohort, and the non-LD comparison cohort comprised age- and sex-matched nondonors. Cumulative incidences and hazard ratios (HRs) were calculated. The overall incidence of PUD was 1.74-fold higher in the LD cohort than in the non-LD cohort (2.14 vs. 1.48 per 1000 person-years). After adjustment for age, sex, monthly income and comorbidities, we determined that the LD cohort exhibited a higher risk of PUD than did the non-LD cohort (adjusted HR 1.74, 95% confidence interval [CI] 1.45-2.09). The incidence of PUD increased with age; the risk of PUD was 2.53-fold higher in patients aged ≥35 years (95% CI 2.14-2.99) than in those aged ≤34 years. LDs with comorbidities of osteopathies, chondropathies and acquired musculoskeletal deformities exhibited a higher risk of PUD (adjusted HR 3.93, 95% CI 2.64-5.86) compared with those without these comorbidities. LDs are associated with an increased risk of PUD after hepatectomy.

Although experimental models have shown that statins could alleviate glomerular damage and decrease urinary protein excretion, the renal effects of statins remain unclear. A case-control study was conducted using data from Taiwan's National Health Insurance system.An end-stage renal disease (ESRD) group comprising 11,486 patients was established. Each patient was frequency-matched by age, sex, and comorbidities with one person without ESRD from the general population. Logistic regression analysis was performed to estimate the influence of statin use on ESRD risk.The overall adjusted odds ratios (ORs) of ESRD among patients who received statins was 1.59 (95% confidence interval=1.50-1.68). The raised ESRD risk of statin remained consolidated regardless of statin type (P.001), except lovastatin. Further, while stratified by cumulative define daily dose, the risk of ESRD increased with accumulative dosage of statins (P for trend.001).This population-based case-control study showed that statin use might be associated with increased ESRD risks. Large-scale randomized clinical trial encompassing statins of different kinds and populations of different comorbidities would be helpful to clarify the potential ESRD risks of statin users.

Meng-Jer Hsieh,1,2 Shu-Yi Huang,1 Tsung-Ming Yang,1 Chi-Wei Tao,3 Shih-Lung Cheng,4 Chao-Hsien Lee,5 Ping-Hung Kuo,6 Yao-Kuang Wu,7,8 Ning-Hung Chen,9 Wu-Huei Hsu,10 Jeng-Yuan Hsu,11 Ming-Shian Lin,12 Chin-Chou Wang,13 Yu-Feng Wei,14 Ying-Huang Tsai1,2 1Department of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Chang-Gung Medical foundation, Chiayi, Taiwan; 2Department of Respiratory Therapy, School of Medicine, Chang-Gung University, Taoyuan, Taiwan; 3Department of Internal Medicine, Cheng Hsin General Hospital, Taipei, Taiwan; 4Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 7Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; 8School of Medicine, Tzu Chi University, Hualien, Taiwan; 9Department of pulmonary and critical care medicine, LinKou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 10Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 11Division of Chest Medicine, Taichung Veterans General Hospital, Taiwan; 12Dpartment of Internal Medicine, Ditmanson Medical Foundation, Chia-Yi Cristian Hospital, Chia-Yi, Taiwan; 13Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang-Gung Medical Foundation, Kaohsiung, Taiwan; 14Department of Internal Medicine E-Da Hospital, I-Shou University, Kaohsiung, Taiwan Background: This nationwide study was performed to evaluate the evolution of distributions of patients with COPD according to the 2011 and 2017 Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines and to assess the concordance between the prescribed medications and the pharmacological management recommended by the two distinct classification systems in Taiwan.Subjects and methods: Data were retrospectively retrieved from stable COPD patients in 11 participating hospitals across Taiwan. Patients were grouped according to GOLD 2011 and 2017 guidelines respectively. Definitions of undertreatment and overtreatment were based on the pharmacological recommendations in the individual guidelines.Results: A total of 1,053 COPD patients were included. The percentages of patients in GOLD 2011 groups A, B, C and D were 18.4%, 40.6%, 6.7% and 34.2%, respectively. When reclassified according to the GOLD 2017, the percentages of group A and B increased to 23.3% and 63.2%, and groups C and D decreased to 1.9% and 11.6%, respectively. Up to 67% of patients in GOLD 2011 groups C and D were reclassified to GOLD 2017 groups A and B. The pharmacological concordance rate was 60.9% for GOLD 2011 and decreased to 44.9% for GOLD 2017. Overtreatment was found in 29.5% of patients according to GOLD 2011 and the rate increased to 46.1% when classified by the GOLD 2017. The major cause of overtreatment was unnecessary inhaled corticosteroids and the main cause of undertreatment was a lack of maintenance long-acting bronchodilators.Conclusion: The distribution of COPD patients in Taiwan was more uneven with the GOLD 2017 than with the GOLD 2011. A pharmacological discordance to the guidelines was identified. Updated guidelines with reclassification of COPD patients resulted in more discordance between prescribed medications and the guidelines. Physicians should make proper adjustments of the prescriptions according to the updated guidelines to ensure the mostly appropriate treatment for COPD patients. Keywords: chronic obstructive pulmonary disease, GOLD guidelines, inhaled corticosteroids, long-acting bronchodilators

Type 1 diabetes mellitus (T1DM) has been linked to many autoimmune problems. The association between T1DM and urticaria warrants investigation. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Participants with T1DM were recruited as the case group, and that group was matched by sex and age at a ratio of 1:4 to the control group comprising those without T1DM. The study period was 1998&ndash, 2011. All participants were followed up to the diagnosis of urticaria, withdrawal from the insurance program, death, or the end of the study. A multivariable Cox proportional hazard model was used to calculate the adjusted and crude hazard ratios for urticaria. A total of 5895 participants (1179 in the case group and 4716 in the control group) were followed up in the study. The total incidence rate of urticaria in patients with type 1 DM was 26.6 per 1000 person-years, and that in controls was 6.85 per 1000 person-years. Compared with the control group, the hazard ratio of urticaria in the case group was 2.84 (95% CI = 2.27&ndash, 3.56). Compared with age-matched participants without T1DM, patients with type 1 DM aged &lt, 18 years had a 3.62-fold higher risk of urticaria (95% CI = 2.85&ndash, 4.59). The hazard ratio in patients with an adjusted Diabetes Complications Severity Index (aDCSI) score of 1.01&ndash, 2.00 per year was 2.57 (95% CI = 1.18&ndash, 5.57), and that in patients with an aDCSI score of &gt, 2.00 per year was 4.47 (95% CI = 2.68&ndash, 7.47). T1DM patients aged &lt, 18 years had an increased risk of urticaria, but a similar phenomenon was not observed among T1DM patients older than 18 years.

Background: A suitable multivariate predictor for predicting mortality following percutaneous coronary intervention (PCI) remains undetermined. We used a nationwide database to construct mortality prediction models to find the appropriate model. Methods: Data were analyzed from the Taiwan National Health Insurance Research Database (NHIRD) covering the period from 2004 to 2013. The study cohort was composed of 3,421 patients with acute myocardial infarction (AMI) diagnosis undergoing PCI. The dataset of enrolled patients was used to construct multivariate prediction models. Of these, 3,079 and 342 patients were included in the training and test groups, respectively. Each patient had 22 input features and 2 output features that represented mortality. This study implemented an artificial neural network model (ANN), a decision tree (DT), a linear discriminant analysis classifier (LDA), a logistic regression model (LR), a naive Bayes classifier (NB), and a support vector machine (SVM) to predict post-PCI patient mortality. Results: The DT model was found to be the most suitable in terms of performance and real-world applicability. The DT model achieved an area under receiving operating characteristic of 0.895 (95% confidence interval: 0.865–0.925), F1 of 0.969, precision of 0.971, and recall of 0.974. Conclusions: The DT model constructed using data from the NHIRD exhibited effective 30-day mortality prediction for patients with AMI following PCI.

Background: Sympathetic activity, including cervical ganglia, is involved in the development of cardiac arrhythmias. Objective: The present study investigated the association between cervical spondylosis and arrhythmia, which has never been reported before. Methods: Patients newly diagnosed with cervical spondylosis (CS) with an index date between 2000 and 2011 were identified from the National Health Insurance Research Database. We performed a 1:1 case-control matched analysis. Cases were matched to controls according to their estimated propensity scores, based on demographics and existing risk factors. Cox proportional hazard models were applied to assess the association between CS and arrhythmia. Results: The CS cohort comprised 22,236 patients (males, 42.6%, mean age, 54.4 years) and non-CS cohort comprised 22,236 matched controls. There were 1441 events of arrhythmia in CS cohort and 537 events of arrhythmia in non-CS cohort, which 252 and 127 events of atrial fibrillation in CS and non-CS cohort, 33 and 12 events of ventricular tachycardia in CS cohort and non-CS cohort, 78 and 35 events of supraventricular tachycardia in CS cohort and non-CS cohort. The CS cohort had an arrhythmia incidence of 11.1 per 1000 person-years and a higher risk [adjusted hazard ratio (aHR) = 3.10, 95% confidence interval (CI) = 2.80&ndash, 3.42] of arrhythmia, 2.54-fold aHR of ventricular tachycardia (95% CI = 1.70&ndash, 3.79), and 2.22-fold aHR of atrial fibrillation (95% CI = 1.79&ndash, 2.76) compared with non-CS cohort. Conclusions: Cervical spondylosis is associated with a higher risk of arrhythmia.

ObjectiveThoracic infection and pneumonia are prevalent in patients with schizophrenia; however, it is unclear whether patients with schizophrenia are at an increased risk of developing pleural empyema.DesignA retrospective cohort study with propensity-matched cohorts with and without schizophrenia.SettingUsing the National Health Insurance Research Database of Taiwan.ParticipantsWe identified 55 888 patients with schizophrenia newly diagnosed in 2000–2011 and same number of individuals without schizophrenia as the comparison cohort, frequency matched by propensity scores estimated using age, sex, occupation, income, urbanisation, year of diagnosis and comorbidities.Primary outcome measuresWe assessed incident pleural empyema by the end of 2011 and used the Cox proportional hazards model to calculate the schizophrenia cohort to comparison cohort HR of pleural empyema.ResultsThe overall incidence of pleural empyema was 2.44-fold greater in the schizophrenia cohort than in the comparison cohort (4.39vs1.80 per 10 000 person-years), with an adjusted HR of 2.87(95% CI 2.14 to 3.84). Stratified analyses by age, sex, occupation, income, urbanisation and comorbidity revealed significant hazards for pleural empyema associated with schizophrenia in all subgroups.ConclusionsPatients with schizophrenia are at an increased risk of developing pleural empyema and require greater attention and appropriate support.

Background: Sitagliptin, a dipeptidyl peptidase-4 inhibitor possibly affects bone turnover. We conducted this cohort study to determine whether sitagliptin is associated with an increased risk of fracture. Methods: The sitagliptin cohort included 1,578 patients aged 20 years and above. The nonsitagliptin cohort comprised propensity-score matched patients at a ratio of 1:1. The primary outcome was the incidence of fractures, which was evaluated using Kaplan–Meier survival analysis and proportional hazards modeling. Results: The mean age of patients in the sitagliptin and nonsitagliptin cohorts was 63.1 and 63.3 years, respectively. The incidence of fractures in the sitagliptin cohort was 46 per 1,000 person-years and that in the nonsitagliptin cohort was 40.8 per 1,000 person-years. Compared with patients in the nonsitagliptin cohort, those in the sitagliptin cohort who received sitagliptin for ≥250 days had a higher risk of fracture (aHR = 1.32, 95% CI = 1.06–1.64). Conclusion: Using sitaglipin ≥250 days was associated with an increased risk of fracture.

Direct evidence of whether thyroid cancer patients have a higher risk of age-related macular degeneration (AMD) has yet to be investigated. Patients older than 50 years-old and newly diagnosed with thyroid cancer between 2000 and 2008 were identified from the national health insurance research database (NHIRD). We applied time-varying Cox proportional hazard models to assess the association between thyroid cancer and AMD. The multivariable models included conventional cardiovascular risk factors, myopia, vitreous floaters, hypothyroidism, hyperthyroidism, and treatment modality of thyroid cancer. The analysis process was stratified by age, gender, and comorbidity. In this study, 5253 patients were included in a thyroid cancer cohort (men 24.5%; median age 59.1 years (53.7–67.4 years), and 21,012 matched controls were included in a non-thyroid cancer cohort. The AMD incidence was 40.7 per 10,000 person/year in the thyroid cancer cohort. The thyroid cancer cohort had a higher risk (adjusted hazard ratio (aHR) = 1.38, 95% confidence interval, CI = 1.09–1.75) of AMD than the non-thyroid cohort. Thyroid cancer patients had a higher risk of AMD, especially the male patients (aHR = 1.92, 95% CI = 1.38–3.14) and the patients with comorbidities (aHR = 1.38, 95% CI = 1.09–1.74). In conclusion, thyroid cancer patients older than 50 years-old have increased risk of AMD.

Objective Data regarding the association between hypoglycemia and attention deficit hyperactivity disorder (ADHD) in children and adolescents with type 1 diabetes mellitus (T1DM) are limited. This study investigated whether hypoglycemia was associated with the risk of ADHD in young people with T1DM. Methods Children and adolescents with a diagnosis of T1DM were identified from the Longitudinal National Health Insurance Database in Taiwan from 1998 to 2011. Among them who were newly diagnosed with hypoglycemia during 2000 to 2007 were selected for the hypoglycemia cohort. The hypoglycemia diagnosis date was defined as the index date. Those who were diagnosed with ADHD before the index date were excluded. The main outcome was the development of ADHD. In total, 726 participants with hypoglycemia and 2852 participants without hypoglycemia were included in this study. Results The overall incidence density of ADHD was markedly increased among cohort with hypoglycemia compared with cohort without hypoglycemia (4.74 vs 1.65 per 1000 person-years), with an adjusted hazard ratio (aHR) of 2.73 (95% confidence interval [CI] = 1.50-4.98). Cohort with hypoglycemia who had experienced a hypoglycemic coma had a significantly higher risk of ADHD (aHR = 6.54, 95% CI = 1.89-22.7) compared with cohort without hypoglycemia. Conclusions Hypoglycemia, especially hypoglycemic coma, is significantly associated with a subsequent risk of ADHD in young people with T1DM.

Background Previous studies have suggested that mycobacterial infections could trigger autoimmune diseases, including rheumatoid arthritis (RA). Objective To explore the association between previous tuberculosis (TB) and RA. Methods We conducted a case-control study using data obtained from the National Health Insurance (NHI) system of Taiwan. We identified 26 535 adults with RA from 2002 to 2011, with the date of diagnosis as the index date. This number was randomly selected and frequency-matched four times by age, sex and the year of index date from among non-RA individuals. Odds ratios (ORs) of RA were calculated for associations with TB. Results Compared with controls, RA patients had a crude OR of 1.77 for TB (95%CI 1.61-1.94). The strength of the association between RA and TB remained at the same level after controlling for other potential risk factors (adjusted OR 1.73, 95%CI 1.57-1.90), although RA patients tended to have a higher prevalence of hypertension, coronary artery disease and kidney disease. Conclusion TB was much more prevalent in RA patients than in control subjects. Prospective cohort studies are required to establish a causal relationship between previous TB and RA.

Study objectives Previous literature lacks the analysis of non-apnea sleep disorder (NASD) and peripheral arterial disease (PAD). The aim of this study was to evaluate the association between NASD and risk of developing PAD using retrospective data from a national database in Taiwan. Design, setting, and participants We identified 46,064 patients with NASD using the catastrophic illness registry of the Taiwan National Health Insurance Research Database (NHIRD) from 1996 to 2010. We also selected a comparison cohort of 92,128 subjects who were randomly frequency-matched by age, sex, and entry year of the NASD cohort from the same database. Interventions non-apnea sleep disorders. Main outcome and measurements The study followed up all subjects from their entry date to the occurrence of PAD. We evaluated the risks of PAD using Cox proportional hazards regression models. The survival function for PAD was assessed using the Kaplan–Meier method. Results The risk of PAD was 1.49-fold in patients with NASD compared with patients without NASD after adjusting for age, sex, and comorbidities. Patients with NASD and diabetes or with NASD and hyperlipidemia had an increased risk of PAD compared to those without NASD and diabetes or hyperlipidemia. Conclusions We demonstrated the significantly increased risk of PAD in NASD patients through a nationwide population-based retrospective cohort study.

BACKGROUND Tuberculosis (TB) is an infectious disease involving multiple organs, including the eyes. We examined the risk of cataract among patients with TB using population data. METHOD Using data from the National Health Insurance (NHI) system of Taiwan, we established a TB cohort with 6994 patients newly diagnosed between 2000 and 2010. For each TB patient, four subjects without TB were randomly selected for the non-TB cohort, frequency matched by age, sex and diagnosis years. The incidence of cataract was measured by the end of 2011. The hazard ratio (HR) of cataract was estimated using Cox proportional hazards regression analysis. RESULTS The overall incidence rate of cataract was 21% greater in the TB cohort than in the non-TB cohort (22.9 vs. 18.8/1000 person-years, P < 0.001), with an adjusted HR (aHR) of 1.26 (95%CI 1.16-1.37). Cataract incidence increased with age, and was higher in men than women and much higher for those with comorbidity. The hazard of cataract was higher in the first 6 months after TB diagnosis. CONCLUSION TB patients are at elevated risk of developing cataract. Although the incidence decreased with time, the aHR remains statistically significant through the follow-up years.

Background & Aims We conducted a nationwide, population-based cohort study to evaluate the effects of inflammatory bowel disease (IBD) on the risks of developing deep vein thrombosis (DVT) and pulmonary embolism (PE) in Taiwan. Methods We randomly selected the study cohort with IBD from the National Health Insurance (NHI) database ( N =23.74 million) and the control cohort without IBD who was frequency-matched the study cohort based on age, sex, and index year to each IBD patient between 2000 and 2010. Using a follow-up period ending in 2011, we analyzed the risks of DVT and PE using Cox proportional hazard regression analyses. Results The 11 445 IBD patients and 45 780controls were followed 65 256 and 293 377 person-years, respectively. After adjusting for age, sex, and comorbidities, the risks of IBD patients developing DVT and PE was 1.98-fold and 1.80-fold higher, respectively, than those of the comparison cohort. The IBD patients presenting with 2 or more annual hospitalizations exhibited a significantly greater risk of developing DVT (adjusted hazard ratio [HR] 32.9, 95% confidence interval [CI] 20.5–52.8) and PE (adjusted HR=24.2, 95% CI=11.1–52.9) than did the comparison cohort. Women with IBD showed a significantly greater risk of DVT and PE than did the comparison cohort (adjusted HR=1.80, 95% CI=1.18–2.78 for DVT and adjusted HR=2.08, 95% CI=1.14–3.80 for PE respectively). Conclusion The risks of DVT and PE are significantly higher in IBD patients compared with risks in the general population. What is current knowledge Thromboembolic complications are easily overlooked in IBD patients. What is new here The risks of DVT and PE are significantly higher in IBD patients.

Background: Studies investigating the epidemiological relationship between Mycoplasma pneumonia (MP) and the subsequent development of acute coronary syndrome (ACS) are scant. We conducted a nationwide longitudinal cohort study in Taiwan to explore whether MP patients are at an increased risk of developing ACS. Methods: This study investigated the incidence and risk factors for ACS in 12 152 newly diagnosed MP patients from the Taiwan National Health Insurance Research Database between 2004 and 2011. The control group consisted of 48 600 individuals without MP. The follow-up period ran from the time of initial MP diagnosis to the date of an ACS event, censoring, or 31 December 2011. We analyzed the risk of ACS by using Cox proportional hazard regression models, including variables for sex, age and comorbidities. Results: The incidence of ACS was higher in MP patients than in comparison cohort (3.08 vs. 2.42 per 1000 person-years). The hazard ratio of developing ACS increased 37% in MP patients compared with that in the comparison cohort after adjustment for covariates. The effect of MP on subsequent ACS development appeared to 12 months after infection. Conclusion: This nationwide study determined that compared with the general population, MP patients exhibited a 37% increase in the risk of subsequently developing ACS. Clinicians should be aware of this risk in MP patients and provide appropriate cardiovascular management in addition to MP treatment.

Objective Studies investigating the relationship between sleep disorders (SDs) and the risk of venous thromboembolism (VTE) are scarce. The present study from Taiwan evaluated whether the risk of VTE was associated with SDs other than sleep apnea. Methods The present study investigated the incidence and risk of VTE in 46,371 people with SDs, compared with 92,742 controls without SDs. The follow-up period began from the date of entering the study cohort to the date of a VTE event, censoring, or December 31, 2011. A Cox proportional hazards regression analysis was conducted to estimate the effects of SDs on the risk of VTE. Results The SD cohort had a 1.79-fold adjusted hazard ratio (HR) of subsequent VTE, compared with the non-SD cohort (95% CI 1.49–2.16). The incidence of VTE increased with age for both cohorts but was higher for those in the SD cohort. However, the adjusted HRs for VTE were significantly higher for the people with SDs aged ≦49 years (HR 3.29, 95% CI 2.12–5.12) and 50–64 years (HR 2.43, 95% CI 1.76–3.35), but were not significant for the oldest group (HR 1.11, 95% CI 0.84–1.47), compared with the controls. The multiplicative increased risk of VTE was significant for the people with SDs with any comorbidity. Conclusion This nationwide cohort study determined that the VTE risk significantly increased in people with SDs compared with those of the general population.

Objectives Few studies have examined the risk of acute coronary syndrome (ACS) in asthmatics. We investigate the effects of asthma on the risk of ACS development in an Asian population. Methods Asthma patients aged ≥ 18 years were identified, and asthma-free controls were randomly selected from the general population and frequency-matched according to age, sex, index year, and baseline comorbidity by using the National Health Insurance Research Database. Both cohorts were followed up until the end of 2011 to measure the incidence of ACS. The risk of ACS was analyzed using Cox proportional hazards regression models. Results We observed the asthmatic patients for 97,506 person–years and followed the nonasthmatic people for 193,423 person–years. The incidence density rate of ACS increased in all groups of the asthmatic patients compared with those of the controls when the data were stratified according to sex, age, and comorbidities. The hazard ratio (HR) of ACS was 1.66-fold greater in the asthmatic cohort than in the nonasthmatic cohort, after adjusting for sex, age, and comorbidities (95% confidence interval [CI]: 1.31–2.11). The adjusted HR of developing ACS increased substantially as age and the frequency of asthmatic exacerbation and hospitalization increased. Conclusions Asthma is an independent risk factor of ACS, and poor control of asthma increases the risk of ACS development in a dose-dependent manner.

Background There is some evidence that the prevalence of depression in patients with tuberculosis (TB) is higher than those in the general population. However, the incidence of depression after Mycobacterium tuberculosis infection remains unknown. Our aim was to assess the association between TB and the subsequent risk of depression. Methods We conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The TB cohort included 9020 patients who were newly diagnosed and recruited between 2000 and 2010. Each patient was randomly frequency-matched for age, sex and the year of index date with four people without TB from the general population. The newly diagnosed depression was followed up until the end of 2011. The relative risks of depression were estimated using Cox proportional hazard models after adjusting for age, sex, index year and comorbidities. Results The overall incidence rate of depression was 1.54-fold higher in the TB cohort as compared with the controlled cohort (8.15 vs. 5.29 per 1000 person-years, 95% confidence interval [CI] = 1.45–1.64). Stratified analyses by gender, age group, monthly income and comorbidities revealed that the adjusted hazard ratio (HR) of depression was higher in males as well as individuals older than 65 years with a low monthly income and comorbidities. Conclusion People who have been diagnosed with TB have a significantly higher risk of developing depression compared with those in the general population. We should pay more attention to this group of individuals and ensure that they are offered appropriate support.

Background & aims Until now, no study has investigated the risks of acute coronary syndrome (ACS) and peripheral arterial disease (PAD) in cirrhosis. Methods In this study, 57,214 patients diagnosed with cirrhosis between 2000 and 2010 were identified from the Taiwan National Health Insurance claims data. Each patient was randomly selected and frequency-matched with an individual without cirrhosis by age, sex, and index year. Results The overall incidence rates of ACS and PAD were 2.81 and 2.97 per 1000 person-years, respectively, in the cirrhosis cohort. The cirrhosis cohort had a higher risk of ACS [adjusted subhazard ratio (aSHR) = 1.12, 95% confidence interval (CI) = 1.03–1.22] and PAD (aSHR = 1.11, 95% CI = 1.02–1.21). The risk of ACS was highest among members of the cirrhosis cohort with ascites (aSHR = 1.09, 95% CI = 1.11–1.19). Conclusions Patients with chronic liver disease and cirrhosis have higher risks of ACS and PAD than those without chronic liver disease and cirrhosis.

Purpose To clarify the relationship between asthma–chronic obstructive pulmonary disease overlap syndrome (ACOS) and depression. Methods We identified 10,911 patients who received an ACOS diagnosis and concurrent treatment between January 2000 and December 2009. Subjects without ACOS were included in the non-ACOS cohort (n = 10,911). Cox proportional hazard regression analysis was performed to compare the risk of depression between the ACOS and non-ACOS cohorts. Results The risk of depression was higher in the ACOS cohort than in the non-ACOS cohort (adjusted hazard ratios (aHRs) = 1.67, 95% confidence interval [CI] = 1.48–1.88). In the ACOS cohort, the aHRs for depression were [2.44 (95% CI = 1.45–4.11); 2.36 (95% CI = 1.58–3.52)] in patients [aged 20–39 years; without comorbidity]. In the ACOS cohort, the aHRs for depression were 1.70 (95% CI = 1.51–1.93) and 1.84 (95% CI = 1.55–2.19) in patients without inhaled corticosteroids (ICSs) and oral steroids (OSs) use, respectively. Moreover, the aHRs for the risk of depression were 1.16 (95% CI = 0.95–1.41) and 1.12 (95% CI = 0.96–1.29) in patients with ICSs and OSs use, respectively. Conclusion The risk of depression is higher in ACOS patients, even in those without comorbidities or in young adults. The events of the depression were not significant difference in patients receiving the ICSs/OSs between the ACOS and the non-ACOS cohorts.