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We would like to thank Dr Lee and Dr Song for their correspondence to our preliminary study recently published in Annals of the Rheumatic Diseases .1 2 Dr Lee and Dr Song have raised some concerns. We make a response as follows. First, the non-ankylosing spondylitis group included persons without a diagnosis code of ankylosing spondylitis (based on International …

The association between systemic lupus erythematosus and other comorbidities has been extensively studied.1 2 Recently, an article written by Orsolini et al published in Annals of the Rheumatic Diseases commented that osteoporosis and fractures are frequently found in patients with systemic lupus erythematosus.3 Orsolini et al ’s article is a timely one and provides the updated concepts to the readers. Some points are discussed here. A cohort study in South Korea conducted by Kim et al reported that the incidence of fractures was higher in patients with systemic lupus erythematosus than those with non-lupus (19 vs 6.5 per 1000 person-years).4 A cohort study in USA conducted by Tedeschi …

Proton pump inhibitors therapy has been found to be associated with some comorbidities.1 Recently, one case-control study disclosed a positive association between tuberculosis and proton pump inhibitors therapy (OR=1.13; 95% CI 1.10 to 1.28),2 which was compatible with another case-control study in Taiwan (OR=1.31; 95% CI 1.22 to 1.41).3 Some points need to be discussed. Proton pump inhibitors and histamine-2 receptor antagonists have similar indications for acid-related gastrointestinal diseases, but little research explores the association between the risk of tuberculosis and histamine-2 receptor antagonists therapy. In order to explore this issue, a preliminary case-control study was conducted …

Ankylosing spondylitis is a systemic inflammatory disease which always influences the spine joints. The association between ankylosing spondylitis and multiple systemic comorbidities has been well assessed.1 2 Recently, one meta-analysis conducted by Mathieu et al published in Annals of the Rheumatic Diseases reported that persons with ankylosing spondylitis were significantly associated with increased risks of myocardial infarction and stroke when compared with controls (risk ratio=1.44 for myocardial infarction, and risk ratio=1.37 for stroke).3 Mathieu et al ’s research is well performed and informative to the readers. Diabetes mellitus is a well-established risk factor for myocardial infarction and stroke. One cross-sectional study reported that 13.64% of persons with ankylosing spondylitis had diabetes mellitus.4 We make a rational hypothesis that diabetes mellitus could be involved in the association between ankylosing …

Statins are commonly used for the treatment of hypercholesterolaemia. The association between statin use and gastric cancer risk has been extensively assessed.1 2 Recently, a cohort study in UK conducted by Spence et al revealed that statin use after a diagnosis of gastric cancer was associated with a lower hazard of cancer-specific death (HR=0.83, 95% CI 0.74 to 0.93).3 This result was partially compatible with that of a cohort study in Republic of Korea showing that statin use for more than 6 months was associated with increased survival rate of gastric cancer compared with non-use (HR=0.168, 95% CI 0.032 to 0.881).4 In order to test the …

Hydroxychloroquine is an immunomodulatory agent which is commonly used to treat malaria and autoimmune diseases.1 The association between hydroxychloroquine therapy and subsequent comorbidities has been extensively addressed.1 2 Recently, a cohort study conducted in the UK by Fardet et al published in Annals of the Rheumatic Diseases reported that long-term use of hydroxychloroquine was not associated with the risk of Alzheimer’s disease when compared with non-use of hydroxychloroquine (adjusted HR=0.81, 95% CI=0.58 to 1.12, p=0.20).3 One comment published in Annals of the Rheumatic Diseases reported that due to conflicting results between observational studies regarding the impact of hydroxychloroquine on Alzheimer’s disease, the relationship cannot be determined currently.4 In order to test such an association in a different population, a …

Proton pump inhibitors are commonly prescribed for the treatment of acid-related gastrointestinal diseases. The association between proton pump inhibitors therapy and other subsequent comorbidities has been extensively explored.1 Recently, a cohort study in USA conducted by Ozen et al published in the Annals of the Rheumatic Diseases reported that proton pump inhibitors therapy was not associated with increased fracture risk in patients with rheumatoid arthritis (HR=0.92; 95% CI 0.80 to 1.06).2 Ozen et al ’s study is an important one and deserves a practical value. Some points not shown in the original article are shared with the readers. First, in order to test …

Allopurinol is commonly prescribed to treat hyperuricemia. The association between allopurinol use and other comorbidities has been widely explored.1 2 Recently one cohort study revealed that no significant association could be detected between allopurinol use and the risk of prostate cancer (HR=1.03; 95% CI 0.92 to 1.16),3 but another cohort study revealed that long-term use of allopurinol for more than 1 year was associated with a lower risk of prostate cancer in men with gout when compared with …

Ankylosing spondylitis is a type of arthritis that commonly affects the joints of the spine. The relationship between ankylosing spondylitis and other diseases has been extensively explored.1 2 Recently, a cohort study in Canada conducted by Avina-Zubieta et al published in Annals of Rheumatic Diseases disclosed that people with ankylosing spondylitis were at higher risk of venous thromboembolism compared with people without ankylosing spondylitis (HR 1.53, 95% CI 1.16 to 2.01).3 Avina-Zubieta et al ’s study is well performed and is informative to the researchers. Some of my views are shared with the readers as follows. First, the overall …

The article by De Pablo-Fernandez et al.1 reported that type 2 diabetes mellitus (DM) was associated with increased hazard of Parkinson disease (PD) (hazard ratio 1.32, 95% confidence interval 1.29–1.35). The authors proposed that DM and PD might share a similar genetic predisposition with potential opportunities to develop therapeutic strategies.1 To the contrary, other studies revealed a negative association or no association between DM and PD.2,3 One meta-analysis revealed data from cohort studies that suggested DM being associated with an increased risk of PD, but case–control studies did not reveal such an association.4 There seems to be no conclusive evidence on this association.

One cohort study revealed that patients with type 2 diabetes with metformin use had a lower risk of developing pancreatic cancer (HR 0.49, 95% CI 0.25 to 0.96).1 One meta-analysis revealed that patients with type 2 diabetes with metformin use had a lower mortality of pancreatic cancer (risk ratio 0.84, 95% CI 0.73 to 0.96) .2 However, one cohort study revealed no significant association between metformin use and pancreatic cancer (HR 0.85, 95% CI 0.39 to 1.89).3 Another cohort study revealed no significant association between metformin use and survival of pancreatic cancer (HR 0.86, 95% CI 0.66 to 1.11).4 Conflicting findings exist on this issue. In order to clarify these debates, a population-based case–control study was designed to analyse the database of …

One article written by Waldum et al. commented that the association between proton pump inhibitors and gastric cancer could be related to hypergastrinemia caused by proton pump inhibitors use [1]. ...

Background and purpose The aim of this study was to explore whether hearing loss is associated with the risk of Parkinson's disease in the elderly in Taiwan. Methods Using claims data of the Taiwan National Health Insurance Program, 4976 patients (aged 65 years or older) with newly diagnosed hearing loss from 2000 to 2010 were identified and 19 904 subjects without hearing loss were randomly selected as comparisons, frequency matched by sex, age and index year of diagnosing hearing loss. The incidence of Parkinson's disease by the end of 2010 and the associated risk factors were investigated. Results The incidence of Parkinson's disease in the hearing loss group was 1.77-fold higher than that in the non-hearing-loss group (3.11 vs. 1.76 per 1000 person-years). After controlling for confounding factors, the adjusted hazard ratio (HR) of Parkinson's disease was 1.53 (95% CI 1.17, 1.99) for the hearing loss group compared with the non-hearing-loss group. Male sex (HR = 1.33, 95% CI 1.02, 1.74), age (for each year, HR = 1.06, 95% CI 1.04, 1.09), hypertension (HR = 1.70, 95% CI 1.26, 2.30) and cerebrovascular disease (HR = 1.78, 95% CI 1.37, 2.32) were also significantly associated with the risk of Parkinson's disease. Conclusions Hearing loss correlates with an increased risk of Parkinson's disease in the elderly. Further studies are needed to confirm whether hearing loss could be a non-motor feature of Parkinson's disease.

Purpose The elderly with non-alcoholic fatty liver disease (NAFLD) are more at risk for cirrhosis, plus even higher mortality. However, few studies of NAFLD focused on the elderly. This study explores prevalence of NAFLD to determine related factors among the elderly in Taiwan. Materials and methods Hospital-based, retrospective cross-sectional study analyzed medical records of elderly patients receiving periodic health examination at a medical center in Taichung, Taiwan, during 2000 to 2004. Subjects with alcoholism, hepatitis B surface antigen positive, or hepatitis C virus antibody positive were excluded. Each subject received anthropometric measurement, biochemical testing, and abdominal ultrasonography; 521 underwent further analysis. Results There were 258 men (49.5%) and 263 women (50.5%), mean age 70.3 ± 4.6 years (range 65–87). Overall NAFLD prevalence was 50.1%, no significant difference between men and women (46.1% vs. 54.0%, P > 0.05). Controlling for covariates, multivariate logistic regression pinpointed factors for NAFLD: generalized obesity (OR = 2.59, 95% CI = 1.50–4.48), central obesity (OR = 1.85, 95% CI = 1.20–2.87), hyperglycemia (OR = 1.50, 95% CI = 1.01–2.23), hypertriglyceridemia (OR = 2.00, 95% CI = 1.22–3.30), and elevated alanine aminotransferase (ALT) (OR = 6.43, 95% CI = 2.00–20.61). Smoking proved negatively correlated with NAFLD (OR = 0.55, 95% CI = 0.31–0.97). Conclusion This study discloses NAFLD prevalence among the elderly in Taiwan as above 50%. Related factors include obesity, hypertriglyceridemia, hyperglycemia, and elevated ALT. Despite the high prevalence in the elderly population, we identified no unique risk factors when comparing with other Oriental and European studies.

Little is known on the relationship between herpes zoster and Parkinson's disease in older people. This study aimed to explore whether herpes zoster could be associated with Parkinson's disease in older people in Taiwan. We conducted a retrospective cohort study using the claim data of the Taiwan National Health Insurance Program. There were 10,296 subjects aged 65 years and older with newly diagnosed herpes zoster as the herpes zoster group and 39,405 randomly selected subjects aged 65 years and older without a diagnosis of herpes zoster as the nonherpes zoster group from 1998 to 2010. Both groups were followed up until subjects received a diagnosis of Parkinson's disease. This follow-up design would explore whether subjects with herpes zoster were at an increased risk of Parkinson's disease. Relative risks were estimated by adjusted hazard ratio (HR) and 95% confidence interval (CI) using the multivariable Cox proportional hazards regression model. The incidence of Parkinson's disease was higher in the herpes zoster group than that in the nonherpes zoster group (4.86 vs 4.00 per 1000 person-years, 95% CI 1.14, 1.29). After adjustment for confounding factors, the multivariable Cox proportional hazards regression model revealed that the adjusted HR of Parkinson's disease was 1.17 for the herpes zoster group (95% CI 1.10, 1.25), compared with the nonherpes zoster group. Older people with herpes zoster confer a slightly increased hazard of developing Parkinson's disease when compared to those without herpes zoster. We think that herpes zoster correlates with increased risk of Parkinson's disease in older people. When older people with herpes zoster seek help, clinicians should pay more attention to the development of the cardinal symptoms of Parkinson's disease.

Little research is available on the relationship between statin use and pyogenic liver abscess. The objective of the study was to determine whether prior use of statins is associated with pyogenic liver abscess. This case-control study was conducted to analyse the claim data of the Taiwan National Health Insurance Program. There were 1828 participants aged 20-84 years with first episode of pyogenic liver abscess from 2000 to 2013 as the cases and 1828 randomly selected participants without pyogenic liver abscess matched with sex, age and index year as the controls. Statin use was defined as 'current', 'recent' or 'past' if the statin prescription was filled ≤3 months, 3-6 months or >6 months before the date of pyogenic liver abscess diagnosis, respectively. Relative risk of pyogenic liver abscess associated with statin use was estimated by the odds ratio (OR) with 95% confidence interval (CI) using the multivariable logistic regression model. After controlling for potential confounders, the adjusted ORs of pyogenic liver abscess were 0.65 for participants with current use of statins (95% CI 0.50, 0.84), 0.74 for participants with recent use of statins (95% CI 0.49, 1.11), and 1.10 for participants with past use of statins (95% CI 0.90, 1.34), compared with participants with never use of statins. In the further analysis, the adjusted ORs of pyogenic liver abscess were 0.65 for participants with cumulative duration of statin use ≥12 months (95% CI 0.48, 0.88) and 0.68 for participants with cumulative duration of statin use

Little is known about the acute effects of furosemide use on the risk of hip fracture. The aim of the present study was to evaluate the association between furosemide use and acute risk of hip fracture in older people in Taiwan.We carried out a retrospective nationwide case-control study using the database of the Taiwan National Health Insurance Program. A total of 4523 older adults aged ≥65 years with newly diagnosed hip fracture from 2000 to 2013 were identified as the cases. Additionally, 4523 older adults aged ≥65 years without hip fracture were randomly selected as the controls. The cases and the controls were matched by sex, age, comorbidities, and index year and month of hip fracture diagnosis. Furosemide use was defined as "current," "recent" or "past" if the furosemide prescription was filled3 months, 3-6 months or ≥6 months before the date of hip fracture diagnosis, respectively. The unconditional logistic regression model was used to calculate the odds ratio and 95% confidence interval (CI) for the relative risk of hip fracture associated with furosemide use.After adjustment for potential covariables, the adjusted odds ratios of hip fracture were 1.30 for participants with current use of furosemide (95% CI 1.14-1.48), 1.23 for participants with recent use of furosemide (95% CI 0.98-1.53) and 1.08 for participants with past use of furosemide (95% CI 0.90-1.30), compared with non-users.Current use of furosemide is associated with a 30% increased odds of hip fracture in older people in Taiwan. Geriatr Gerontol Int 2017; 17: 2552-2558.

Background: We investigated the association between cardiovascular disease (CVD) and the risk of major osteoporotic fracture in Taiwan. Methods: Using the Taiwan National Health Insurance Database for the period 2000–2007, we classified 43874 patients aged 50 years or older with newly diagnosed CVD (coronary artery disease, heart failure, cerebrovascular disease, or peripheral atherosclerosis) as the CVD group and 43874 subjects without CVD (frequency-matched by sex, age, and date selected) as the non-CVD group. Incidence and hazard ratios (HRs) for major osteoporotic fracture of the spine, hip, humerus, and forearm/wrist were estimated for the period until the end of 2010. Results: After adjustment for confounders, the overall HRs for major osteoporotic fracture were 1.24 (95% CI = 1.13, 1.36) in men with CVD and 1.18 (95% CI = 1.11, 1.25) in women with CVD, as compared with the nonCVD group. As compared with the non-CVD group, the adjusted HR for major osteoporotic fracture was highest among subjects with cerebrovascular disease (HR 1.31; 95% CI 1.23, 1.39), followed by those with heart failure (HR 1.18; 95% CI 1.11, 1.27), peripheral atherosclerosis (HR 1.12; 95% CI 1.04, 1.20), and coronary artery disease (HR 1.07; 95% CI 1.01, 1.12). Conclusions: CVD is associated with risk of major osteoporotic fracture in men and women in Taiwan.

Background This study was conducted to evaluate the risk of developing acute pancreatitis (AP) and the fatality from AP in hemodialysis (HD) and peritoneal dialysis (PD) patients, using the claims data of Taiwan National Health Insurance. Methods From patients with newly diagnosed end-stage renal disease (ESRD) in 2000–2010, we identified a PD cohort ( N = 9,766), a HD cohort ( N = 18,841), and a control cohort ( N = 114,386) matched by sex, age, and the diagnosis year of the PD cohort. We also established another 2 cohorts with 9,744 PD patients and 9,744 propensity score-matched HD patients. The incident AP and fatality from AP were evaluated for all cohorts by the end of 2011. Results The adjusted hazard ratios (HRs) of acute pancreatitis were 5.68 (95% confidence interval [CI] = 5.05 – 6.39), 4.91 (95% CI = 4.32 – 5.59), and 7.47 (95% CI = 6.48 – 8.62) in the all dialysis, HD, and PD patients, compared with the controls, respectively. Peritoneal dialysis patients had an adjusted HR of 1.41 (95% CI = 1.21 – 1.65) for AP, compared with propensity score-matched HD patients. Peritoneal dialysis patients under icodextrin treatment had a lower incidence of AP than those without the treatment, with an adjusted HR of 0.59 (95% CI = 0.47 – 0.73). There was no significant difference in the 30-day mortality from AP between HD and PD patients. Conclusions Peritoneal dialysis patients were at a higher risk of developing AP than HD patients. Icodextrin solution could reduce the risk of developing AP in PD patients.

Background This population based study investigated the relationship between use of selective serotonin reuptake inhibitors (SSRIs) and hip fractures in the elderly in Taiwan. Methods Analysis of a random sample of 1 million insurance enrollees' data identified 4,891 patients with newly diagnosed hip fractures and 4,891 controls without hip fracture between 2000 and 2011. Both cases and controls were ≥65 years of age and were matched by sex, age, comorbidities, and index year of hip fracture diagnosis. Patients were considered current SSRI users if their last SSRI tablet was taken ≤7 days before the hip fracture diagnosis. Late use of SSRIs was defined as taking the last SSRI tablet ≥8 days before the hip fracture diagnosis. Non-SSRI users comprised individuals who never had an SSRI prescription. Odds ratios (ORs) and 95% confidence intervals (CIs) for hip fracture associated with SSRI use was estimated by multivariate unconditional logistic regression. Results After adjustment for covariants, multivariate regression analysis showed that the adjusted OR of hip fracture was 2.17 for current SSRI users (95% CI: 1.60–2.93) compared with those who never used SSRIs. The adjusted OR was 1.11 for individuals with late use of SSRIs (95% CI: 0.96–1.28) and was not significant. Conclusions Current use of SSRIs was associated with a 2.17-fold increase in the odds of hip fracture in the elderly in Taiwan. Clinicians should consider the possibility of SSRI-associated hip fracture among old people currently taking SSRIs.

Introduction: Turnover of physicians might be responsible for reducing patients’ trust and affecting hospital performance. This study aimed to understand physicians’ psychological status regarding their hospital work environment and the resources of independent practitioners. Method: This was a cross-sectional study with 774 physicians who had resigned from hospitals and were now practicing privately in clinics in Taichung City as its study population. A mail survey with a multidimensional questionnaire was sent to each subject. Results: This study revealed that older physicians were less satisfied regarding the work environment in their respective former hospitals. Male physicians were found to be more satisfied with the tangible resources of their hospitals. Internal medicine physicians were found to be less satisfied overall with the intangible resources. Gynecologists and pediatricians were found to be more satisfied with their hospital environments. The physicians who worked long hours per week reported that they were less satisfied with their job content. The physicians who had opportunities to learn advanced skills and enhance their knowledge were more satisfied with their hospital environment, tangible resources, and intangible resources. In addition, physicians in private hospitals were found to be more satisfied with their job content, but they were less satisfied with work motivation and retention and intangible resources. In addition, physicians who worked in hospitals located in Taichung city reported that they were less satisfied with their tangible resources than the physicians working in hospitals outside of the city. Conclusion: This study focused on the satisfaction of physicians who had already left their respective hospitals instead of current retained physicians. From this study, it is our recommendation that hospital managers should pay closer attention to the real needs and expectations of the physicians they employ, and managers should consider adjusting their managerial perspectives when establishing new human resources policies or making decisions.

The correlation between simvastatin use and acute pancreatitis is explored. A case-control study was conducted to analyze claim data from the Taiwan National Health Insurance Program. The case group comprising a total of 3882 subjects aged 20 to 84 years with their first acute pancreatitis episode occurring between 1998 and 2011 formed the case group, against 3790 randomly selected controls matched for sex, age, comorbidities, and index year of acute pancreatitis diagnosis. Recent use of simvastatin was defined as subjects whose last remaining simvastatin tablet was noted ≤7 days before the date of acute pancreatitis diagnosis. Remote use of simvastatin was defined as subjects whose last remaining 1 tablet for simvastatin was noted7 days before the date of acute pancreatitis diagnosis. Never use of simvastatin was defined as subjects who had never been prescribed simvastatin. A multivariable unconditional logistic regression model was used to estimate the odds ratio and 95%CI to explore the correlation between simvastatin use and acute pancreatitis. After adjustment for confounders, multivariable logistic regression analysis revealed that the adjusted odds ratio of acute pancreatitis was 1.3 for subjects with recent use of simvastatin (95%CI 1.02, 1.73), when compared with those with never use of simvastatin. The crude odds ratio decreased to 1.1 for those with remote use of simvastatin (95%CI 0.93, 1.34) but without statistical significance. Recent use of simvastatin is associated with acute pancreatitis. Clinicians should consider the possibility of simvastatin-associated acute pancreatitis for patients presenting for acute pancreatitis without known cause.

Little is known about the relationship between proton pump inhibitors use and pyogenic liver abscess. The objective of this study was to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess in Taiwan. This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. Subjects aged 20 to 84 who experienced their first episode of pyogenic liver abscess were enrolled as the case group (n = 1372). Randomly selected subjects aged 20 to 84 without pyogenic liver abscess were enrolled as the control group (n = 1372). Current use, early use, and late use of proton pump inhibitors was defined as subjects whose last one tablet for proton pump inhibitors was noted ≤30 days, between 31 to 90 days and ≥91 days before the date of admission for pyogenic liver abscess. Subjects who never received a prescription for proton pump inhibitors were defined as nonusers of proton pump inhibitors. A multivariable unconditional logistic regression model was used to measure the odds ratio and 95% confidence interval to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess. After adjusting for confounders, the adjusted odds ratio of pyogenic liver abscess was 7.59 for subjects with current use of proton pump inhibitors (95% confidence interval 5.05, 11.4), when compared with nonusers. Current use of proton pump inhibitors is associated with a greater risk of pyogenic liver abscess.

The aim of this study was to assess a possible correlation between zolpidem use and acute pyelonephritis (APN) in women in Taiwan. Therefore, we performed a case-control study involving the Taiwan's National Health Insurance Research Database between 2000 and 2011. This study included 3151 female participants aged 20 to 84 years who experienced the first bout of APN (case group) and 6015 randomly selected female participants without APN (control group). Zolpidem use was defined as "current," "early," or "late," if the last remaining 1 tablet for zolpidem was detected within 7 days, between 8 and 14 days, or ≥15 days before the date of APN diagnosis, respectively. The multivariable unconditional logistic regression model was used to calculate the odds ratios (ORs) with 95% confidence intervals (CIs) to assess the correlation between zolpidem use and APN. After adjusting for confounders, the multivariable analysis yielded an adjusted APN OR of 2.2 for participants with current zolpidem use (95%CI 1.7-2.8) compared with participants who never used zolpidem. The adjusted ORs gradually decreased to 1.4 for participants with early zolpidem use (95%CI 0.8-2.5) and 1.1 for participants with late zolpidem use (95%CI 0.9-1.2), but without statistical significance. Only patients with current zolpidem use had a significantly increased relative risk of APN. Additional large confirmatory studies are needed to illustrate a causal relationship. Meanwhile, physicians and pharmacists should be more cautious about the risk of APN when prescribing and dispensing zolpidem in women.

Background The aims of this study were to assess the prevalence of elevated alanine aminotransferase (ALT) and explore its related factors in Central Taiwan. Methods The study employed a retrospective design. The study selected a sample of 5,550 subjects between the years 2000 to 2004. The indivduals undergoing health examinations in a medical center in Central Taiwan were enrolled as subjects for this research. The patients’ demographics, smoking and drinking habits, laboratory findings, and abdominal ultrasound results were collected and analyzed. Correlations between variables were analyzed using SPSS/ PC Windows for frequency distribution, t-test, Chi-square test, and multivariate logistic regression. Results There were 3103 men (55.9%) and 2447 women (44.1%). The mean age was 49.4 ± 12.3 years (age range of 20-87). The overall prevalence of elevated ALT was 17.1%, with a significant gender difference (23.2% in men vs. 9.4% in women, P < .0001). The multivariate logistic regression analysis showed that the factors significantly related to elevated ALT were central obesity, hypertriglyceridemia, and anti-HCV positive in men and women. Conclusions Central obesity, hypertriglyceridemia, and anti-HCV positive are factors predominantly related to elevated ALT in men and women.

Background and objective Clinical evidence is scarce about the relationship between losartan use and acute pancreatitis. We therefore conducted a population-based case–control study using the database from the Taiwan National Health Insurance Program to investigate this question. Methods The study consisted of 1449 hypertensive subjects aged 20–84 years with a first episode of acute pancreatitis during the period 2000–2011 as the case group and 2479 hypertensive subjects without acute pancreatitis as the control group. Both the case and control groups were matched for sex, age, comorbidities and index year of acute pancreatitis diagnosis. According to the history of losartan prescription before the date of diagnosis of acute pancreatitis, subjects who had never received a prescription for losartan were defined as ‘never use of losartan’, those whose last remaining losartan tablet was detected within 7 days before the date of diagnosis of acute pancreatitis were defined as ‘current use of losartan’ and those whose last remaining tablet of losartan was detected ≥8 days before the date of diagnosis of acute pancreatitis were defined as ‘late use of losartan’. ORs and 95% CIs were measured to investigate the risk of acute pancreatitis associated with losartan use by the multivariable unconditional logistic regression model. Results After adjustment for potentially confounding factors, the adjusted OR of acute pancreatitis was 0.96 (95% CI 0.68 to 1.37) for subjects with current use of losartan compared with those with never use of losartan, but the difference was not statistically significant. For subjects with late use of losartan the adjusted OR of acute pancreatitis was 1.05 (95% CI 0.80 to 1.37), which also was not statistically significant. Conclusions No significant association can be detected between losartan use and acute pancreatitis in hypertensive patients. More research is required to determine the potential role of losartan in the risk of acute pancreatitis.

Background and Aim: A metric that predicts the presence of cancer-related liver disease would allow early implementation of treatment. We compared the demographic and clinical characteristics of patients with no evidence of liver disease, with a cancer-associated liver disease, and with a liver disease not associated with cancer. Methods: Retrospective, hospital-based, cross-sectional study which reviewed the medical records of subjects who underwent health examinations at a Taiwanese hospital from 2000 to 2004 and who had normal levels of amino transaminases. Demographic and clinical data were analyzed by univariate and multivariate statistics. Results: A total of 2344 subjects had no evidence of liver disease (non-LD), and 1918 subjects had at least one liver disease (LD). The LD group was further divided into those with a cancer-associated liver disease (LD-1, n = 1632) and those with a liver disease not associated with cancer (LD-2, n = 286). Age, BMI, percentage of males, globulin:albumin ratio (G/A), percentage of patients with gallstones, AST, and ALT were significantly higher in the LD group. Univariate analysis showed that the G/A was significantly higher in the LD-2 group than the LD-1 group; multivariate analysis indicated that the G/A was not independently associated with liver disease, but that subjects who were older and had higher BMI were significantly more likely to have a cancer-associated liver disease. Conclusions: For patients with liver disease, a multivariate model can be used to distinguish those with a cancer-associated liver disease from those with a liver disease not associated with cancer.

The causal association between diabetes and pancreatic cancer remains unclear in Asian populations. This study examined whether gallstones, a cholecystectomy, chronic pancreatitis and the treatment of antidiabetic agents affect the risk of subsequent pancreatic cancer for patients with diabetes in a Taiwanese population. Using claims data from the universal health insurance program in Taiwan, 449,685 newly diagnosed diabetic cases among insured people from 2000 to 2003 were identified as the case group. The comparison group, matched for gender, age, and the index year of the diabetes cohort, consisted of 325,729 persons without diabetes. Pancreatic cancer incidence was measured in both groups until the end of 2008. Other risk factors associated with this cancer were also measured. The incidence of pancreatic cancer in the diabetic cohort was 2-fold greater than that in the comparison group (1.46 vs. 0.71 per 10,000 person-years) with an adjusted hazard ratio (HR) of 1.75 [95 % confidence interval (CI) 1.45–2.10]. The risk slightly increased for diabetic patients with gallstones, cholecystitis, and a cholecystectomy (HR 1.92, 95 % CI 1.18–3.11), but greatly increased for those with comorbidity of chronic pancreatitis (HR 22.9, 95 % CI 12.6–41.4). Pancreatic cancer risk also increased significantly for those patients who used more insulin for treating diabetes (OR 2.20, 95 % CI 1.40–3.45). Our data suggest that the risk of pancreatic cancer is moderately increased in patients with diabetes, especially those using insulin therapy. The risk is greatly increased for diabetic patients with chronic pancreatitis.

Background and Aim: This study investigated whether diabetes mellitus (DM) increased the risk of pancreatic cancer and whether anti-diabetic drugs reduced the risk in Taiwan. Methods: We designed a population-based cohort study using the Taiwan National Health Insurance Database, which consisted of 49 803 patients aged 20 years and older with newly diagnosed DM as the diabetic group and 199 212 people without DM as the non-diabetic group during 1998-2007. Results: The incidence of pancreatic cancer was higher in patients with diabetic duration less than 2 years, as compared to the non-diabetic group (27.81 vs 6.96 per 10 000 person-years, 95% confidence interval = 2.11-7.54). Age (aged 40-64, hazard ratio (HR) = 5.22, and aged 65 and older, HR = 7.59, respectively), chronic pancreatitis (HR = 19.40), gallstones (HR = 2.56), and hepatitis C infection (HR = 3.08) were also significant factors predicting pancreatic cancer. Patients with concurrent DM and chronic pancreatitis had an appreciably elevated risk of developing pancreatic cancer (HR = 33.52), as compared with subjects without these comorbidities. The association was not statisti- cally significant between use of anti-diabetic drugs and the risk of pancreatic cancer. Conclusions: Diabetes < 2 years' duration is associated with pancreatic cancer and could be an early manifestation of pancreatic cancer. Long-standing diabetes was not found to be a risk factor for pancreatic cancer in Taiwan's patients. Old age, chronic pancreatitis, gallstones and hepatitis C infection are other risk factors for pancreatic cancer. These high-risk patients should undergo close follow-up programs for pancreatic cancer.

Background The risk of some forms of cancer has been found to be higher in patients with diabetes mellitus (DM) than in the general population. The aim of this study was to examine, with sufficient statistical power, the association between DM and lung cancer and the impact of antidiabetes drugs on lung cancer risk in Taiwan. Materials and Methods From a randomly selected data set of 1 million National Health Insurance (NHI) claims in Taiwan from 2000-2005, 19,624 cases (patients ≥ 20 years of age) of newly diagnosed DM were identified. From the same data set, 78,496 enrollees with no record of DM were selected as controls and were matched in sex and age to the first group. The incidence of newly diagnosed lung cancer was compared between patients with DM and controls for a period of 9 years (2000-2008). Results The multivariate Cox model analysis showed a slightly increased hazard ratio (HR) of 1.05 of lung cancer in patients with DM, but the association was not statistically significant. However the use of antidiabetes drugs, such as metformin, thiazolidinediones, or alpha-glucosidase inhibitors, correlates with a decreased lung cancer risk of 39%-45%. A significant association was found between lung cancer risk and male sex (HR, 2.23), pulmonary tuberculosis (HR, 1.60), chronic obstructive pulmonary disease (HR, 1.21), and age (HR, 1.07). Conclusion Patients with DM are not at increased risk for the development of lung cancer, but the use of antidiabetes drugs would considerably decrease the risk. In this cohort, male sex, age, pulmonary tuberculosis, and chronic obstructive pulmonary disease were all associated with an increased risk of lung cancer, consistent with findings in the literature and indicative of the validity of our study.

Aim: The aim of the present study was to investigate whether polypharmacy correlates with the risk of dementia in older people. Methods: From representative claims data established from the National Health Insurance with a population coverage rate of 99% in Taiwan, we identified 7135 newly diagnosed patients with dementia in 2000–2008 and 2 8540 randomly selected controls without dementia, both aged ≥65 years. The daily use of prescribed drugs in the past 2 years was compared between cases and controls, controlling for demographic characters and comorbidities. Results: The incidence of dementia increased with the number of medications used and age. Cases were older than controls, predominant with women and more likely to use five or more drugs daily (44.0% vs 32.0%, P

A new circuit structure is proposed for design of dual- band bandpass fllters with a wide upper stopband. The unit cell of the circuit consists of two two-port networks in shunt connection; one is a coupled-line section of ‚/4 long followed by a transmission line segment of identical length, and the other has the same elements but cascaded in reverse order, where ‚/4 is the wavelength at arithmetic mean frequency of the two passbands. Higher-order circuits can be obtained by directly cascading two or more such cells and show improved frequency selectivity. In addition to on both sides of the passbands, transmission zeros are also created in the rejection bands. Analysis of the unit cell circuit is formulated by the transmission line theory, and design curves for one- and two-cell circuits are provided. In realization, interdigital capacitors are incorporated with the ‚/4 coupled sections for compensating the efiect of unequal modal phase velocities on the fllter performance in the rejection band. Two circuits are fabricated and measured to validate the analysis.

Using population-based representative insurance claims data, the risk of developing hepatocellular carcinoma (HCC) among diabetes mellitus (DM) patients, as well as whether DM medications alter the risk of developing HCC were investigated.From the Taiwan National Health Insurance Research Database, 19,349 newly diagnosed DM patients 20 years and older and 77,396 comparison subjects without DM were identified from claims from 2000 to 2005. The incidences of HCC at the end of 2008 and the risks associated with hepatitis B and hepatitis C were determined. Whether metformin and thiazolidinediones reduce the risk of developing HCC was also measured.The incidence of HCC was twice higher in the DM group compared with the non-DM group (21.0 vs. 10.4 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.73 (95% confidence interval (CI)=1.47-2.03) using multivariable Cox proportional hazard regression. Male sex, cirrhosis, hepatitis B, and hepatitis C were significant independent factors that predict HCC, with HRs of 2.32, 8.65, 2.52, and 5.61, respectively. In the stratified analysis, the HR increased to 72.4 (95% CI=42.9-122) among patients with DM, cirrhosis, and hepatitis C. HCC risk reduction was greater for diabetics taking metformin than those taking thiazolidinediones (51 vs. 44% reduction).Comorbidity with cirrhosis and/or hepatitis appears to be associated with an extremely increased risk of developing HCC among DM patients. These high-risk patients should be closely monitored for HCC. The use of metformin or thiazolidinediones may reduce the risk of developing HCC.

The objective of this study was to assess the risk of acute pancreatitis among patients with type 2 diabetes mellitus (DM) and identify the roles of co-morbidities and anti-diabetic drugs.From claims data of one million enrollees randomly sampled from a population covered by the Taiwan National Health Insurance, 19,518 adults with type 2 DM diagnosed between 2000 and 2005 were identified. In addition, 78,072 DM-free persons, frequency matched with sex, age, and index year for comparison were identified. Subjects were followed up until the end of 2008 or censored to ascertain incident acute pancreatitis cases and associations with co-morbidities and anti-diabetic drugs.Patients with type 2 DM had 1.95-fold greater incidence of acute pancreatitis compared with non-diabetics (27.7 vs. 14.2 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.89 (95% confidence interval (CI)=1.65-2.18) based on multivariable Cox regression analysis. Additive Poisson regression analysis revealed an absolute risk increase of 14.4 per 10,000 person-years (95% CI=13.4-15.5) among type 2 DM patients. Co-morbid alcoholism, hepatitis C infection, and gallstones yielded additional risk of acute pancreatitis among type 2 DM patients (absolute risk increase ranges 86.3, 41.1, and 23.5 per 10,000 person-years, respectively). Patients taking anti-diabetic drugs had a reduced risk of acute pancreatitis, however. The adjusted HR decreased to 0.31 (95% CI=0.18-0.56) among patients who took five different anti-diabetic drugs.Patients with type 2 DM are at an elevated risk of acute pancreatitis. Alcoholism, hepatitis C infection, and gallstones increase the risk further. However, anti-diabetic drugs reduce the risk as the number of drugs used increases and as the duration of treatment increases.

Background: Little is known about the relationship between polypharmacy and Parkinson's disease (PD). In the present study, we tested the hypothesis that polypharmacy increases the risk of PD in older people in Taiwan. Methods: From a randomly sampled cohort of one million health insurance enrollees, we identified 2827 new cases of PD over the period 2000–2008 aged ≥65 years and selected 11 308 age-matched controls without PD. Medication history and baseline comorbidities were compared between the two groups. We defined ‘polypharmacy’ as an average daily use of five or more prescribed drugs. Results: Compared with patients using between none and one drug, the odds ratios (ORs) for PD increased to 1.53, 2.08, 2.64, and 2.95 for patients using two to four, five to seven, eight to nine, and ≥10 drugs, respectively. The other conditions associated with PD were dementia (OR 3.43), stroke (OR 2.30), depression (OR 2.15), and alcoholism (OR 2.11). Hyperlipidemia (OR 0.90) was inversely associated with PD. Conclusions: Polypharmacy was shown to increase the risk of PD in older people in Taiwan, with risk increasing with the number of medications taken daily. Dementia, stroke, depression, and alcoholism were also associated with an increased risk of PD, whereas there was an inverse correlation between PD and hyperlipidemia.

The relationship between tamoxifen use and acute myocardial infarction in women with breast cancer remains uncertain. The goal of the study was to assess whether tamoxifen use could be associated with acute myocardial infarction in women with breast cancer in Taiwan. A population-based case–control study was conducted to analyze the database of the Taiwan National Health Insurance Program. Totally, 489 women with breast cancer aged 20 to 84 years having the first episode of acute myocardial infarction from 2000 to 2011 were found as the cases. In addition, 1718 women with breast cancer aged 20 to 84 years without any type of ischemic heart disease were selected as the matched controls. Ever use of tamoxifen was classified as the studied women who had at least a prescription for tamoxifen before the index date. Never use of tamoxifen was classified as the studied women who never had a prescription for tamoxifen before the index date. We used the multivariable logistic regression model to estimate the odds ratio (OR) and 95% confidence interval (CI) for acute myocardial infarction associated with tamoxifen use. In a multivariable-adjusted analysis, women with acute myocardial infarction were 1.71 times more likely to be exposed to tamoxifen than those women without acute myocardial infarction (adjusted OR 1.71, 95% CI 1.38–2.13). The odds of tamoxifen use are 1.71 times higher in women with acute myocardial infarction versus those women without acute myocardial infarction in Taiwan.

The association between tamoxifen use and risk of deep vein thrombosis or pulmonary embolism in women with breast cancer has been reported in the Western population. The study aimed to evaluate the association between tamoxifen use and deep vein thrombosis or pulmonary embolism in older women with breast cancer in Taiwan.We conducted a retrospective case-control study using the database of the Taiwan National Health Insurance Program. A total of 281 women subjects with breast cancer aged ≥65 years with newly diagnosed deep vein thrombosis/or pulmonary embolism from 2000 to 2011 were identified as the cases. Additionally, 907 women subjects with breast cancer aged ≥65 years without deep vein thrombosis or pulmonary embolism were randomly selected as the controls. The cases and the controls were matched with age and comorbidities. Ever use of tamoxifen was defined as subjects who had at least a prescription for tamoxifen before index date. Never use of tamoxifen was defined as subjects who never had a prescription for tamoxifen before index date. We used the multivariable logistic regression model to calculate the odds ratio (OR) and the 95% confidence interval (CI) of deep vein thrombosis or pulmonary embolism associated with tamoxifen use.After adjustment for confounding variables, the adjusted OR of deep vein thrombosis or pulmonary embolism was 1.95 for subjects with ever use of tamoxifen (95% CI 1.45, 2.62), as compared with never use of tamoxifen. In addition, atrial fibrillation (adjusted OR 3.73, 95% CI 1.89, 7.35) and chronic kidney disease (adjusted OR 1.72, 95% CI 1.06, 2.80) were also associated with deep vein thrombosis or pulmonary embolism.Tamoxifen use is associated with 1.95-fold increased odds of deep vein thrombosis or pulmonary embolism among older women with breast cancer in Taiwan.

Background/Aim: No published nation-based study has examined the relationship between weight loss and cancer in Taiwan. The aim of this study was to investigate whether weight loss is an early clinical manifestation of cancer in Taiwan. Methods: We conducted a nation-based, retrospective cohort study that analyzed the database of the Taiwan National Health Insurance Program. There were 8210 subjects aged 20 to 84 years with newly diagnosed weight loss selected as the weight loss group from 2000 to 2012, and 32826 randomly selected subjects without weight loss as the non-weight loss group. The weight loss and non-weight loss groups were matched along sex, age, and comorbidities. The incidence of cancer at the end of 2013 was examined in both groups. Results: The weight loss group had a significantly higher incidence of cancer than the non-weight loss group during the first 3 months of follow-up (25.1 vs. 8.39 per 1000 person-years, with an incidence rate ratio 2.99, 95% CI 2.82, 3.18). The multivariable Cox proportional hazards regression model revealed that the adjusted HR of cancer was 1.05 for the weight loss group (95% CI 1.04, 1.05) as compared with the non-weight loss group. Conclusion: Weight loss is associated with a small but statistically significant increase in the hazard of cancer. Weight loss might be an early clinical manifestation of undiagnosed cancer. Physicians should keep in mind the possibility of cancer when people present with weight loss and other possible cancer-related symptoms, particularly during the first 3 months of follow-up.