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Abstract Background Thiazide-associated hyponatremia (TAH) has been supposed to increase the risk of major adverse cardiovascular events (MACE) in the elderly. Therefore, this study aimed to evaluate the association of TAH with the risk of MACE in elderly Taiwanese patients. Methods Data from the longitudinal generation tracking database (LGTD 2010) of the Health and Welfare Data Science Center (HWDC) were retrospectively assessed. The TAH study group was defined as using > 30 cumulative daily defined doses (CDDDs) thiazide diuretics within one year before diagnosis of hyponatremia. The control group (1:3 propensity score matching) had no diagnosis of hyponatremia but had used > 30 CDDDs thiazide diuretics within one year. Data on MACE were extracted using International Classification of Diseases codes. Outcomes were assessed using a multivariable Cox proportional hazard model and Kaplan-Meier analysis. Results A total of 1155 and 3465 individuals were enrolled in the TAH and the control groups, respectively. The rates of MACE (11.1% vs. 7.3%) and death (22.8% vs.12.2%) were significantly higher in the TAH group than the control group. In the TAH group, the adjusted HRs were 1.29 (CI 1.01 ‒ 1.65) for MACE, 1.39 (CI 1.19 ‒ 1.63) for all-cause death, and 1.61 (CI 0.90 ‒ 2.92) for stroke. Conclusion TAH in patients above 65-years-old is associated with a 29% higher risk of MACE, 39% higher risk of all-cause death, and 61% higher risk of stroke. This work suggests that thiazides prescription in elderly patients should be more careful. However, further research is required to confirm our findings.

Conclusion: This case-control study reveals that there is a statistically significant association between polycystic ovary syndrome and pancreatic cancer. More studies are needed to provide robust evidence.

Objective. To investigate the potential association between nonalcoholic fatty liver disease (NAFLD) and colon polyps in Taiwan. Methods. We utilized 2006–2015 claims data of the Taiwan National Health Insurance Program as a data source. A case-control study was conducted, involving individuals 20 years or older with and without colon polyps. Cases comprised individuals diagnosed with colon polyps, identified through diagnosis codes. Controls were selected from individuals without colon polyps, matched to cases based on sex, age, and comorbidities. NAFLD was identified based on diagnosis codes. The logistic regression model with odds ratio (OR) and 95% confidence interval (CI) was employed to assess the association between NAFLD and colon polyps. Results. The study included 16,890 cases with colon polyps and 67,560 matched controls without colon polyps. The mean age was 57 years old and about 61% of study subjects were males. Among cases with colon polyps, 1.0% had a diagnosis of NAFLD, whereas only 0.4% exhibited NAFLD in the control group. After adjustment for confounding variables, a multivariable logistic regression model revealed a statistically significant association between NAFLD and colon polyps, with an odds ratio of 2.32 (95% CI = 1.91–2.82). Conclusion. This case-control study suggests a positive association between NAFLD and colon polyps. These results contribute to our understanding of the potential links between NAFLD and gastrointestinal health.

ObjectiveTo assess the relationship between use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the risk of gout among patients with type 2 diabetes mellitus (T2DM).MethodsA systemic review and meta-analysis were designed by reviewing articles published between 2000 January 1 and 2022 December 31 using PubMed system and Web of Science system based on the PRISMA 2020 guidelines. The end point of interest was gout (including gout flares, gout events, starting uric-acid lowering therapy and starting anti-gout drugs use) among patients with T2DM using SGLT2i versus not using SGLT2i. A random-effects model was utilized to measure the pooled hazard ratio (HR) with 95% confidence interval (CI) for the risk of gout associated with SGLT2i use.ResultsTwo prospective post-hoc analyses of randomized controlled trials and 5 retrospective electronic medical record-linkage cohort studies met the inclusion criteria. The meta-analysis demonstrated that there was a decreased risk of developing gout for SGLT2i use as comparing with non-use of SGLT2i among patients with T2DM (pooled HR=0.66 and 95%CI=0.57-0.76).ConclusionsThis meta-analysis demonstrates that SGLT2i use is associated with a 34% decreased risk of developing gout among patients with T2DM. SGLT2i may be the treatment options for patients with T2DM who are at high risk of gout. More randomized controlled trials and real-world data are needed to confirm whether there is a class effect of SGLT2i for the risk reduction of gout among patients with T2DM.

Background/Aims: Many Japanese institutions use electromagnetic extracorporeal shock wave lithotripsy (ESWL) systems for treating pancreatic duct stones. However, there are no reports on direct comparisons between recent electromagnetic lithotripters. This study aimed to verify whether the new electromagnetic lithotripter can improve the efficiency of pancreatic stone fragmentation, and to clarify the role of combined endoscopic treatment on the clearance of pancreatic duct stones. Methods: We retrospectively identified 208 patients with pancreatolithiasis who underwent endoscopic adjunctive treatment after pancreatic ESWL at a single Japanese center over a 17-year period. We evaluated the outcome data of this procedure performed with SLX-F2 (last 2 years; group A) and Lithostar/Lithoskop (first 15 years; group B), as well as additional endoscopic treatments for pancreatolithiasis. We also performed logistic regression analysis to detect various factors associated with the procedure. Results: For pancreatic head stones, ESWL disintegration was achieved in 93.7% of group A patients and 69.0% of group B patients (p=0.004), and adjunctive endoscopic treatment removed stones in 96.8% of group A patients and 73.0% of group B patients (p=0.003). Multivariate analysis revealed that lithotripter type (odds ratio, 6.99; 95% confidence interval, 1.56 to 31.33; p

Objective To assess whether there is a relation between allopurinol use and the probability of type 2 diabetes mellitus (T2DM) in persons with gout and/or hyperuricemia. Methods According to the PRISMA 2020 guidelines, a meta-analysis was performed by searching literature published from 2000 to 2021 in two electronic databases (Ebscohost and PubMed). The end point was set as a new diagnosis ofT2DM between people with the use of allopurinol and people with non-use of allopurinol. The random-effects model was performed to evaluate the pooled hazard ratio (HR) with 95% confidence interval (CI) for T2DM associated with allopurinol use. Results Three cohort studies could meet the inclusion criteria in the meta-analysis. There was a high heterogeneity of the outcome between studies (I 2 = 99%). The research duration ranged from 13 to 16 years. The subject number in each work ranged from 1114 to 138,652. A meta-analysis disclosed that there was not an association between allopurinol use and the risk of developing T2DM (pooled HR = 1.01 and 95%CI = .55–1.84). Conclusions The meta-analysis shows that no correlation is detected between allopurinol use and the risk of T2DM in individuals with gout and/or hyperuricemia. Because there are not enough eligible studies, the strength of evidence in our meta-analysis is weak. More cohort studies are needed to determine an association between use of allopurinol and the probability of T2DM for individuals with gout and/or hyperuricemia.

ABSTRACT The food we eat not only nourishes our bodies but also provides nutrients to the bacteria living in our guts. Gut bacterial communities are known to be affected by many factors, including diet and bowel cleansing, but the impacts of vegetarian and omnivore diets on fecal bacterial composition are still uncertain. In this study, we analyzed the bacterial compositions of fecal samples from vegetarians and omnivores 5 to 7 days after bowel cleansing, and we correlated specific dietary constituents with the relative abundances of specialized fecal bacteria. A total of 46 participants (23 vegetarians and 23 omnivores) were recruited. All participants underwent standard bowel cleansing before colonoscopy screening. Fecal samples were collected from each participant 5 to 7 days after bowel cleansing, and the fecal microbiota compositions were analyzed with next-generation sequencing. Sixteen participants also provided an image-based dietary record for nutritional assessment. No major differences between dietary groups were observed in terms of fecal bacterial richness, alpha diversity, or beta diversity. A minority of potential pathobionts tended to be elevated in omnivores compared to vegetarians, whereas potential probiotic species tended to be higher in the vegetarians. Detailed dietary assessments further revealed that the plant- and animal-derived proteins may oppositely modulate the relative abundances of pathobionts Bilophila and Lachnoclostridium. However, these results were not statistically significant after multiple-comparison correction. These results suggest that specialized probiotic and pathobiont microbiota constituents are sensitive to the plant- or animal-derived dietary components ingested by vegetarians and omnivores after bowel cleansing. IMPORTANCE Dietary pattern and food choice are associated with expansion of gut pathobionts and risk for metabolic and colonic disease. However, the effects of dietary interventions on intestinal microbiota remain unclear. After bowel cleansing, potential pathobionts and probiotic bacteria were increased in omnivores and vegetarians, respectively. The pathobionts Bilophila and Lachnoclostridium were oppositely modulated by dietary animal and plant protein. From a clinical perspective, fecal pathobionts that may indicate risk for metabolic and colonic disease can potentially be modulated with dietary interventions.

Objective: The study aimed to thoroughly address the influence of benzbromarone and allopurinol on the risk of the development of type 2 diabetes mellitus (T2DM) in people with asymptomatic hyperuricemia.Methods: We conducted a retrospective cohort study to examine the 2000–2015 national dataset containing all claims data of 23 million beneficiaries in Taiwan. Subjects who already had diabetes mellitus, gout-related diseases, and any cancer prior to the index date were excluded. Asymptomatic hyperuricemia was defined as subjects taking urate-lowering drugs who never had a gout flare. Subjects aged 20–84 with asymptomatic hyperuricemia who had benzbromarone prescriptions were selected as the benzbromarone group. Sex-matched and age-matched subjects with asymptomatic hyperuricemia who had allopurinol prescriptions were identified as the allopurinol group. The maximum follow-up duration was set as 5 years in our study. The outcome was set as subjects who had a new diagnosis of T2DM. The incidence density of T2DM was calculated in the benzbromarone and allopurinol groups. The hazard ratio (HR) and 95% confidence interval (CI) for T2DM was utilized to estimate the association between medications and the risk of T2DM.Results: The incidence of T2DM among benzbromarone users was significantly lower than that of allopurinol users (7.91 versus 8.48 per 100 person-years, incidence rate ratio = 0.93, and 95% CI = 0.87–0.99). After adjustment for co-variables, the adjusted HR of T2DM would be 0.91 (95% CI = 0.85–0.98 and p = 0.008) in benzbromarone users as compared to allopurinol users.Conclusion: There is a small but statistically significant risk reduction of developing T2DM in people with asymptomatic hyperuricemia taking benzbromarone as compared to those taking allopurinol during 5 years of follow-up. It indicates a future research direction for the use of individual urate-lowering drugs on the prevention of T2DM in the general population.

Objective: There is controversy about the association between the allopurinol use and the risk of acute myocardial infarction. The aim of the study was to examine the association between allopurinol use and acute myocardial infarction in older people in Taiwan. Materials and Methods: We used the 2000–2013 database of the Taiwan National Health Insurance Program to conduct a case–control study. Cases were assigned as subjects aged 65 years and older with the first incident acute myocardial infarction. Matched controls were assigned as subjects aged 65 years and older without any type of coronary artery disease. Ever use of allopurinol was defined as subjects who had at least a prescription of allopurinol before the diagnosis date of first incident acute myocardial infarction. The odds ratio (OR) and the 95% confidence interval (CI) for acute myocardial infarction associated with allopurinol use were estimated by the multivariable logistic regression model. Results: There were 4701 cases with the first incident acute myocardial infarction and 9369 matched controls. The adjusted OR of acute myocardial infarction was 2.2 (95% CI 1.7– 2.7) for subjects with ever use of allopurinol, compared with never use. The adjusted ORs of acute myocardial infarction were 2.0 (95% CI 1.5–2.6) for subjects with average daily dosage of allopurinol

Background/Objective: Some case series and case report have shown the association between the risk of acute pancreatitis and use of selective serotonin reuptake inhibitors. The results of systematic studies were not consistent. Methods: A meta-analysis was performed to investigate the risk of acute pancreatitis associated with use of selective serotonin reuptake inhibitors. Results: There was no statistical association between the risk of acute pancreatitis and selective serotonin reuptake inhibitors use (odds ratio: 1.19, 95% confidence interval: 0.93-1.51). Conclusions: Despite reaching no statistical significance, the possibility of the association between the risk of acute pancreatitis and selective serotonin reuptake inhibitors use cannot be totally excluded.

Background/Aims: Radix Angelica Sinensis (danggui in Chinese) is widely used in traditional chinese medicine (TCM). N-butylidenephthalide (BP), a bioactive compound in danggui, is a potential antitumor agent for various cancer types. However, its clinical effect and mechanism in the treatment of gastric cancer remain undetermined. Methods: The in vivo protective effect of danggui in patients with gastric cancer were validated using data from Taiwan’s National Health Insurance Research Database (NHIRD). The genes induced by BP-treatment were analyzed by whole transcriptome RNA sequencing (RNA-seq) and validated by real-time PCR, western blot and siRNA transfection. The effect of BP on AGS cell migration and invasion was evaluated in transwell assays. The antitumor effects of BP were evaluated in vivo in an AGS xenograft animal model. Results: Danggui users were found to have an increased survival rate when compared with danggui nonusers (log-rank test p = 0.002) . The use of danggui highly associated with decreased mortality (the adjusted hazard ratio (HR) of danggui user was 0.72 [95 % CI, 0.57-0.92] (p = 0.009). The in vitro results showed that BP inhibited gastric cancer cell proliferation, and triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Using RNA-seq analysis we found that REDD1 was the highest transcript induced by BP in gastric cancer cells. BP induce an increase of REDD1 expression that inhibits mTOR signaling, thus inhibiting gastric cancer growth. We used RNA interference to demonstrate that the knock-down of REDD1 attenuated the BP-induced mTORC1 activation and growth inhibition. BP suppressed the growth of AGS xenografts tumor in vivo. Conclusion: Danggui can prolong the survival rate of gastric cancer patients in Taiwan. BP caused gastric cancer cell death through the activation of mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR signal pathway inhibition in gastric cancer cells. BP inhibited the in vivo growth of AGS xenograft tumors. These results may provide the basis for a new therapeutic approach toward the treatment of gastric cancer progression.

BACKGROUND: People without a spleen are particularly susceptible to various overwhelming infections including pneumonia. Although the association between splenectomy and pneumonia has been previously studied, there has been no study using the national claims data. OBJECTIVES: The aim of the study was to investigate the association between splenectomy and pneumonia. DESIGN: A retrospective population-based cohort analysis. SETTINGS: Database of the Taiwan National Health Insurance Program. PATIENTS: Persons newly diagnosed with splenectomy from 2000 to 2010 were compared with randomly selected subjects without splenectomy. The groups were matched by sex, age, comorbidities, and the year of index date and analyzed by multivariate methods. MAIN OUTCOME MEASURE: The difference in incidence of pneumonia at the end of 2011. RESULTS: In 12 757 individuals aged 20-84 years with splenectomy, the overall incidence of pneumonia was 1.86-fold higher than in the 51 019 individuals without splenectomy (25.0 vs. 13.4 per 1000 person-years, 95% CI 1.78, 1.95). After multivariate analysis, the adjusted hazard ratio for pneumonia was 2.2 for subjects with splenectomy (95%CI 2.07, 2.34). In further analysis, in the absence of any comorbidity, the adjusted HR for pneumonia was 3.03 for those with splenectomy alone (95% CI 2.76, 3.33) and 5.28 (95% CI 4.82, 5.78) for splenectomy and any comorbidity. CONCLUSIONS: Although not a novel finding, we confirmed that splenectomy increases the relative risk for developing pneumonia in a large study population. Even in the absence of any comorbidity, the risk remains high. Patients with splenectomy should receive preventive interventions for pneumonia, such as vaccination. LIMITATIONS: ICD-9 codes do not differentiate if pneumonia is caused by a viral, a bacterial or unspecified organisms, and some behavioral factors like smoking could not be ascertained directly.

Background and Objective: The aim of the study was to investigate whether use of selective serotonin reuptake inhibitors (SSRIs) was associated with pulmonary tuberculosis. Methods: The case–control study was conducted to analyze the database between 2000 and 2013. Patients aged 20 to 84 years with newly diagnosed pulmonary tuberculosis were selected as the cases (n = 8593). Participants without pulmonary tuberculosis were selected as the controls (n = 43 472). Patients who never had a prescription for SSRIs were defined as never use. Those who ever had a prescription for SSRIs were defined as ever use. Results: The adjusted odds ratio (OR) of pulmonary tuberculosis was 1.03 for patients with ever use of SSRIs (95% confidence interval [CI]: 0.93-1.14), compared to never use. The adjusted OR of pulmonary tuberculosis was 1.00 for patients with increasing cumulative duration of SSRI use for every 1 month (95% CI: 0.99-1.00), compared to never use. The adjusted OR of pulmonary tuberculosis was 0.99 for patients with increasing cumulative dosage of SSRI use for every 1 mg (95% CI: 0.99-1.00), compared to never use. Conclusion: No significant association can be detected between SSRI use and pulmonary tuberculosis in Taiwan. No duration-dependent effect or dose-dependent effect of SSRIs use can be detected on the risk of pulmonary tuberculosis.

Hispolon, a polyphenol compound isolated from Phellinus linteus, has been reported to exhibit antioxidant, antiproliferative, and antitumor activities. This study aimed to explore the antitumor effects of hispolon on glioblastoma multiforme (GBM) cells in vitro and in vivo. The results revealed that hispolon significantly inhibited GBM cell proliferation and induced apoptosis through caspase-9 and caspase-3 activation and PARP cleavage. Hispolon also induced cell cycle G2/M phase arrest in GBM cells, as supported by flow cytometry analysis and confirmed by a decrease in cyclin B1, cdc2, and cdc25c protein expressions in a dose- and time-dependent manner. Furthermore, hispolon suppressed the migration and invasion of GBM cells by modulating epithelial–mesenchymal transition (EMT) markers via wound healing, transwell assays, and real-time PCR. Moreover, hispolon significantly reduced tumor growth in DBTRG xenograft mice and activated caspase-3 in hispolon-treated tumors. Thus, our findings revealed that hispolon is a potential candidate for the treatment of GBM.

No formal epidemiological research based on systematic analysis has focused on the relationship between herpes zoster and immunodeficiency virus (HIV) infection in Taiwan. Our aim was to explore whether herpes zoster is an early manifestation of undiagnosed human HIV infection in Taiwan. Methods: This was a retrospective cohort study using the database of the Taiwan National Health Insurance Program. A total of 35,892 individuals aged ≤ 84 years with newly diagnosed herpes zoster from 1998 to 2010 were assigned to the herpes zoster group, whereas 143,568 sex-matched and age-matched, randomly selected individuals without herpes zoster served as the non-herpes zoster group. The incidence of HIV diagnosis at the end of 2011 was estimated in both groups. The multivariable Cox proportional hazards regression model was used to estimate the hazard ratio and 95% confidence interval (CI) for risk of HIV diagnosis associated with herpes zoster and other comorbidities including drug dependence and venereal diseases. Results: The overall incidence of HIV diagnosis was 4.19-fold greater in the herpes zoster group than that in the non-herpes zoster group (3.33 per 10,000 person-years vs. 0.80 per 10,000 person-years, 95% CI 4.04–4.35). The multivariable Cox proportional hazards regression analysis revealed that the adjusted hazard ratio of HIV diagnosis was 4.37 (95% CI 3.10–6.15) for individuals with herpes zoster and without comorbidities, as compared with individuals without herpes zoster and without comorbidities. Conclusion: Herpes zoster is associated with HIV diagnosis. Patients who have risk behaviors of HIV infection should receive regular surveillance for undiagnosed HIV infection when they present with herpes zoster.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Regorafenib is a multi-kinase inhibitor and the second-line treatment for HCC. Since the PI3K/Akt/mTOR signaling pathway is dysregulated in HCC, we evaluated the therapeutic effects of regorafenib combined with a dual PI3K/mTOR inhibitor BEZ235 in the human HCC cell lines (n = 3). The combined treatment with BEZ235 and regorafenib enhanced the inhibition of cell proliferation and increased the expression of cleaved caspase-3 and cleaved PARP in HCC cells. Moreover, the combined treatment suppressed HCC cell migration and invasion in the transwell assay. Further, the Western blot analyses confirmed the involvement of epithelial-mesenchymal transition (EMT)-related genes such as slug, vimentin, and matrix metalloproteinase (MMP)-9/-2. Additionally, the proteinase activity of MMP-9/-2 was analyzed using gelatin zymography. Furthermore, the inhibition of phosphorylation of the Akt, mTOR, p70S6K, and 4EBP1 after combined treatment was validated using Western blot analysis. Therefore, these results suggest that the combined treatment with BEZ235 and regorafenib benefits patients with HCC.

Objectives: Little is known about the risk of pyogenic liver abscess in patients with splenectomy. We explored the relationship between splenectomy and pyogenic liver abscess in Taiwan. Methods: We conducted a nationwide cohort analysis using the hospitalization dataset of the Taiwan National Health Insurance Program. We included 17 779 subjects aged 20–84 years who underwent splenectomy in 1998 to 2010 (splenectomy group) and 70 855 randomly selected subjects without splenectomy (non-splenectomy group). Both groups were matched by sex, age, other comorbidities, and hospitalization year of receiving splenectomy. The incidence of pyogenic liver abscess at the end of 2011 was measured. The multivariable Cox proportional hazard regression model was used to estimate the hazard ratios and 95% confidence intervals for pyogenic liver abscess associated with splenectomy and other comorbidities. Results: The overall incidence rate was 3.75-fold higher in the splenectomy group than that in the non-splenectomy group (2.15 vs 0.57 per 1000 person-years; 95% confidence interval, 3.57–3.94). After controlling for potential confounding factors, the adjusted hazard ratio of pyogenic liver abscess was 3.89 in subjects with splenectomy (95% confidence interval, 3.20–4.72) when compared with subjects without splenectomy. In further analysis, the hazard ratio markedly increased to 14.34 for those with splenectomy and having any of the assessed comorbidities, including alcoholism, biliary stone, chronic kidney disease, chronic liver diseases, and diabetes mellitus (95% confidence interval, 10.61–19.39). Conclusions: Patients with splenectomy are at an increased risk of developing pyogenic liver abscess, particularly when they have comorbid conditions.

Background: It remains unknown whether hearing loss increases the risk of Alzheimer’s disease. This study aimed to examine the association between hearing loss and risk of Alzheimer’s disease in older people in Taiwan. Methods: Analyzing the database from Taiwan’s National Health Insurance Program, this case-control study enrolled 488 subjects ≥65 years old with newly diagnosed Alzheimer’s disease as a case group and 1952 subjects without Alzheimer’s disease as a control group from 1998–2011. Patients with Alzheimer’s disease and other comorbidities were identified by analyzing ICD-9 coding in claims data. The association of hearing loss, other comorbidities, and risk of Alzheimer’s disease were compared between groups. Results: After controlling for confounders, multivariable logistic regression showed an adjusted odds ratio of Alzheimer’s disease of 1.39 in people with hearing loss (95% CI, 1.05–1.84) versus those without. Parkinson’s disease (OR 4.44; 95% CI, 2.54–7.78), head injury (OR 2.31; 95% CI, 1.46–3.66), depression (OR 1.68; 95% CI, 1.19–2.39), hypertension (OR 1.40; 95% CI, 1.10–1.79), and age (each year, OR 1.03; 95% CI, 1.01–1.05) also showed strong links with Alzheimer’s. Conclusions: Hearing loss is associated with increased risk of Alzheimer’s disease in older people in Taiwan.

Objectives: The purpose of the study was to assess the relationship between selective serotonin reuptake inhibitors use and hepatocellular carcinoma in Taiwan.Methods: Using the database of the Taiwan National Health Insurance Program, we conducted a case-control study to identify 4901 subjects aged 20 years and more with newly diagnosed hepatocellular carcinoma in 2000–2013 as the cases. We randomly selected 19604 subjects aged 20 years and more without hepatocellular carcinoma as the controls. Both cases and controls were matched with sex and age. Ever use of selective serotonin reuptake inhibitors was defined as a subject who had at least a prescription for selective serotonin reuptake inhibitors before index date. Never use was defined as a subject who never had a prescription for selective serotonin reuptake inhibitors before index date. The odds ratio (OR) and 95% confidence interval (CI) for hepatocellular carcinoma associated with selective serotonin reuptake inhibitors use was estimated by the multivariable logistic regression model.Results: Among subjects with any one of the comorbid conditions associated with hepatocellular carcinoma, the adjusted OR of hepatocellular carcinoma was 0.89 (95% CI 0.75, 1.06) for subjects with ever use of selective serotonin reuptake inhibitors, comparing with never use.Conclusion: The findings indicate that among subjects with any one of the comorbid conditions associated with hepatocellular carcinoma, no significant association can be detected between selective serotonin reuptake inhibitors use and hepatocellular carcinoma.

Background and Objectives: Limited research focuses on the risk of ischemic cerebrovascular disease associated with use of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) in patients with type 2 diabetes mellitus in Taiwan. This study aimed to investigate the association between DPP-4 inhibitors use and the first episode of ischemic cerebrovascular disease.Methods: We designed a case-control study using the database of the Taiwan National Health Insurance Program. There were 1999 type 2 diabetic subjects aged 20–84 years with the first episode of ischemic cerebrovascular disease from 2000 to 2013 as the cases, and 7996 sex- and age-matched, randomly selected type 2 diabetic subjects aged 20–84 years without any type of cerebrovascular diseases as the matched controls. We estimated the odds ratio (OR) and 95% confidence interval (CI) of ischemic cerebrovascular disease associated with cumulative duration of DPP-4 inhibitors use by the multivariable logistic regression model.Results: After adjustment for confounding variables, the adjusted OR of ischemic cerebrovascular disease was 0.96 (95% CI 0.95, 0.97) in subjects with ever use of DPP-4 inhibitors as increase in use duration for every 1 month, compared with never use. The sub-analysis disclosed that the adjusted ORs of ischemic cerebrovascular disease were 1.57 (95% CI 1.36, 1.80) for subjects with cumulative duration of DPP-4 inhibitors use

Background/objectiveTuberculosis (TB) and depression were major public health issues worldwide and the mutual causative relationships between them were not exhaustive. This study was performed to explore the association between depression, comorbidities, and the risk of pulmonary TB in Taiwan.MethodsThe cohort study used the database of the Taiwan National Health Insurance Program. The depression group included 34,765 subjects aged 20–84 years with newly diagnosed depression from 2000 to 2012, and the non-depression group included 138,187 randomly selected subjects without depression. Both depression and non-depression groups were matched with respect to sex, age, and comorbidities. We explored the incidence of pulmonary TB at the end of 2013 in both the groups and used multivariable Cox proportional hazards regression model to explore the hazard ratio (HR) and 95% confidence interval (CI) for the risk of pulmonary TB associated with depression.ResultsThe overall incidence of pulmonary TB was 1.16-fold greater in the depression group than that in the non-depression group (1.52 vs. 1.31 per 1,000 person-years, 95% CI 1.12, 1.21). The multivariable Cox proportional hazards regression analysis revealed that the adjusted HR of pulmonary TB was 1.15 for the depression group (95% CI 1.03, 1.28), compared with the non-depression group.ConclusionDepression is associated with 1.15-fold increased hazard of pulmonary TB in Taiwan.

Background and Objectives: There are inconsistent results about the association between ischemic cerebrovascular disease and tamoxifen use in women with breast cancer. The study aimed to evaluate the association between the risk of ischemic cerebrovascular disease and tamoxifen use in older women with breast cancer in Taiwan.Methods: We designed a retrospective, nationwide, case-control study using the database of the Taiwan National Health Insurance Program. A total of 800 female subjects with breast cancer aged ≥65 years with the first episode of ischemic cerebrovascular disease from 2000 to 2011 were identified as the cases. Additionally, 2,876 female subjects with breast cancer aged ≥65 years without any type of cerebrovascular diseases were selected as the control subjects. The cases and the control subjects were matched with age and comorbidities. Ever use of tamoxifen was defined as a subject who had at least a prescription for tamoxifen before the index date. Never use of tamoxifen was defined as a subject who never had a prescription for tamoxifen before the index date. We used the multivariable logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) for ischemic cerebrovascular disease associated with tamoxifen use.Results: After adjusting for confounding variables, the adjusted OR of ischemic cerebrovascular disease was 2.5 for subjects with ever use of tamoxifen (95% CI 2.10, 2.97), compared with never use of tamoxifen. In addition, the adjusted OR of ischemic cerebrovascular disease was 1.15 (95% CI 1.10, 1.21) in subjects with ever use of tamoxifen as increase in use duration per 1 year. The adjusted OR of ischemic cerebrovascular disease was 2.54 (95% CI 2.03, 3.17) in subjects with ever use of tamoxifen as increase in dosage per 1 mg.Conclusions: Tamoxifen use is significantly associated with 2.5-fold increased odds of ischemic cerebrovascular disease among older women with breast cancer in Taiwan. There are duration-dependent and dose-dependent effects of tamoxifen use on the risk of ischemic cerebrovascular disease.

Objective: Few studies are available on the association between gallstones and metformin use. The objective of the study was to determine whether metformin use is associated with gallstones.Methods: A population-based retrospective cohort study was conducted using the database of the Taiwan National Health Insurance Program. Subjects of newly diagnosed diabetes mellitus were included from 2002 to 2013. The metformin-exposure group was defined as ≥29 cumulative defined daily dose (DDD) of metformin use. The un-exposure group was defined as 180 cumulative DDD, compared with the un-exposure group.Conclusion: Long-term use of metformin is associated with reduced risk of gallstones.

Background/Objectives: Previous studies showed that zolpidem use could be associated with increased cancer risk, but the role of zolpidem on hepatocellular carcinoma (HCC) risk remains undetermined. The study purpose was to examine the association between HCC risk and zolpidem use in Taiwan.Methods: Using the database from the Taiwan National Health Insurance Program, we designed a case-control study which consisted of 77986 subjects aged 20 years or older with newly diagnosed HCC as the case group, and 77986 subjects without HCC as the control group, from 2000 to 2011. Ever use of zolpidem was defined as a subject who had at least a prescription for zolpidem before the index date. Never use was defined as a subject who did not have a prescription for zolpidem before the index date. The association between HCC risk and zolpidem use was determined by the odds ratio (OR) and 95% confidence interval (CI) in a multivariable logistic regression model.Results: After adjustment for confounding factors, the adjusted OR of HCC was 1.05 (95% CI 0.97, 1.13) for subjects with ever use of zolpidem, compared with never use of zolpidem. The adjusted OR of HCC was 1.01 for subjects with increasing cumulative duration of zolpidem use for every 1 year (95% CI 0.99, 1.03), compared with never use of zolpidem.Conclusion: There is no significant association between HCC risk and zolpidem use. There is no duration-dependent effect of zolpidem use on HCC risk.

Aim: Little is known regarding the relationship between use of oral corticosteroids and hip fracture in the elderly in Taiwan. The aim of the study was to examine this issue.Methods: A retrospective population-based case-control study using the database of the Taiwan National Health Insurance Program (2000–2013) was conducted. We identified 4538 individuals aged ≥ 65 years with newly diagnosed hip fracture as the cases. We randomly selected 4538 individuals without hip fracture as the control subjects. The cases and the control subjects were matched with sex, age, comorbidities, and the year of index date. Individuals who never had a prescription for oral corticosteroids were defined as never use. Individuals who ever had at least one prescription for oral corticosteroids were defined as ever use. The odds ratio (OR) and 95% confidence interval (CI) of hip fracture associated with oral corticosteroids use was estimated by a multivariable unconditional logistic regression analysis.Results: After adjustments for potential confounding factors, the multivariable logistic regression model showed that the adjusted OR of hip fracture was 1.17 for individuals with ever use of oral corticosteroids (95%CI 1.08, 1.28), compared to those with never use of oral corticosteroids. An sub-analysis showed that for every 1-mg increase in cumulative dose of oral corticosteroids, the adjusted OR of hip fracture was 1.01 (95% CI 1.01, 1.02). The adjusted ORs were 1.31 (95% CI 1.17, 1.47) for cumulative exposure to oral corticosteroids ≥ 3 months and 1.09 (95% CI 0.98, 1.20) for cumulative exposure < 3 months.Conclusion: We conclude that oral corticosteroids use is associated with a trivial but statistically significant increase in risk of hip fracture in Taiwan. Additionally, the results suggest that there are dose-response and duration-response effects of oral corticosteroids on the risk of hip fracture. The results confirm our understanding of oral corticosteroid-associated hip fracture in the elderly.

Background and Objectives: Little is known about the association between tamoxifen use and Alzheimer’s disease in women with breast cancer. The study aimed to explore the association between tamoxifen use and Alzheimer’s disease in aged women with breast cancer in Taiwan.Methods: We conducted a retrospective nationwide case-control study using the database of the Taiwan National Health Insurance Program. Totally, 173 female subjects with breast cancer aged ≥ 65 years with newly diagnosed Alzheimer’s disease from 2000 to 2011 were identified as the cases. Additionally, 684 female subjects with breast cancer aged ≥ 65 years without any type of dementia were selected as the matched controls. The cases and the matched controls were matched with age and comorbidities. Ever use of tamoxifen was defined as subjects who had at least a prescription for tamoxifen before the index date. Never use of tamoxifen was defined as subjects who never had a prescription for tamoxifen before the index date. We used the logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) of Alzheimer’s disease associated with tamoxifen use.Results: The OR of Alzheimer’s disease was 3.09 for subjects with ever use of tamoxifen (95% CI 2.10, 4.55), compared with never use. The OR of Alzheimer’s disease was 1.23 for subjects with increasing cumulative duration of tamoxifen use for every 1 year (95% CI 1.13, 1.34), compared with never use.Conclusion: The increased odds of Alzheimer’s disease associated with tamoxifen use may be due to the survival effect, not the toxic effect. That is, the longer the tamoxifen use, the longer the patients survive, and the greater the likelihood that she may have a chance to develop Alzheimer’s disease.

Background and Objectives: Little evidence is available about the relationship between statins use and pulmonary tuberculosis in Taiwan. The aim of the study was to explore this issue.Methods: Using the database of the Taiwan National Health Insurance Program, we conducted a population-based case-control study to identify 8,236 subjects aged 20 years and older with newly diagnosed pulmonary tuberculosis from 2000 to 2013 as the cases. We randomly selected 8,236 sex-matched and age-matched subjects without pulmonary tuberculosis as the controls. Subjects who had at least one prescription of statins before the index date were defined as “ever use.” Subjects who never had one prescription of statins before the index date were defined as “never use.” The odds ratio (OR) and 95% confidence interval (CI) for pulmonary tuberculosis associated with statins use was estimated by a multivariable logistic regression model.Results: After adjustment for co-variables, the adjusted OR of pulmonary tuberculosis was 0.67 for subjects with ever use of statins (95% CI 0.59, 0.75). In a sub-analysis, the adjusted ORs of pulmonary tuberculosis were 0.87 (95% CI 0.69, 1.10) for subjects with cumulative duration of statins use

Background and Objectives: Although the relationship between the use of proton pump inhibitors (PPIs) and pulmonary tuberculosis (TB) in Taiwan published in 2014. Due to just only one article and not enough comprehensively, we explore this issue.Methods: We conducted a population-based case-control study to identify 9,422 subjects aged 20 years or older with newly diagnosed pulmonary TB in 2000–2013 as test cases. We then randomly selected 9,422 subjects aged 20 years or older without pulmonary TB as controls. Both cases and controls were matched in terms of sex, age, and comorbidities. Use of PPIs were defined as subjects who had had at least one prescription for these medications before the index date. No use was defined as subjects who had never had a prescription for PPIs before the index date. The odds ratio (OR) and 95% confidence interval (CI) for pulmonary TB associated with PPI use was estimated using the logistic regression model.Results: The OR of pulmonary TB was 1.31 for subjects who had used PPIs (95% CI 1.22, 1.41) compared with those with no use of the medications. Sub-analysis revealed the OR of pulmonary TB in subjects using PPI per increasing microgram was 1.25 (95% CI 1.19, 1.30).Conclusions: PPI use is associated with a 1.3-fold increase in odds of developing pulmonary TB in Taiwan. There is a dose-related response between PPI use and pulmonary TB.

Objectives: The aim of this study was to explore the association between the use of statins and esophageal cancer in Taiwan. Methods: We designed a case–control study using database from the Taiwan National Health Insurance program. In all, 549 patients (cases) aged 20 years or older diagnosed recently with esophageal cancer, from 2000 to 2009, and 2,196 subjects (controls) without esophageal cancer participated in this study. The association between esophageal cancer and the use of statins and other co-morbidities was measured. Results: After adjustment for covariates, multivariate logistic regression showed that patients with a cumulative duration of ≥ 12 months of using atorvastatin might have a reduced risk of esophageal cancer, compared with those who did not use statins (odds ratio [OR] 0.14, 95% confidence interval [CI] 0.04–0.56). The other statins could not show a significant association with esophageal cancer. Age (OR 1.01, 95% CI 1.00–1.01), alcoholism (OR 3.83, 95% CI 3.01–4.89), and esophageal diseases (OR 4.60, 95% CI 3.46–6.12) were independent factors significantly associated with esophageal cancer. Conclusions: Use of atorvastatin ≥ 12 months may correlate with an 86% reduction of esophageal cancer risk.

N-Butylidenephthalide (BP), which is extracted from a traditional Chinese medicine, Radix Angelica Sinensis (danggui), displays antitumor activity against various cancer cell lines. The purpose of this study was to investigate the cytotoxic and radiosensitizing effect of BP and the underlying mechanism of action in human breast cancer cells. BP induces apoptosis in breast cancer cells, which was revealed by the TUNEL assay; the activation of caspase-9 and PARP was detected by western blot. In addition, BP-induced G2/M arrest was examined by flow cytometry and the expression levels of the G2/M regulatory protein were detected by western blot. BP also suppresses the migration and invasion of breast cancer cells, which was tested by wound healing and the matrigel invasion assay; the involvement of EMT-related gene expressions was detected by real-time PCR. Furthermore, BP enhanced the radiosensitivity of breast cancer cells, which was measured by the colony formation assay and comet assay, where the foci of γ-H2AX after radiation significantly increased in BP pretreated cells and was evidenced by immunocytochemistry staining and western blot. The homologous recombination (HR) repair protein Rad51 was down-regulated after BP pretreatment. These results indicate that BP might be a potential chemotherapeutic and radiosensitizing agent for breast cancer therapy.

In this present study, we found that the use of rosuvastatin with cumulative using duration >12 months could correlate with 2.8-fold increased risk of lung cancer in women. We did not have specific comments on these results. Further prospective clinical studies of statins use are needed to elucidate this issue.

The goal of this study was to investigate the association between gout and Parkinson's disease in older people in Taiwan. Utilizing the Taiwan National Health Insurance database, this case–control study included 3854 patients aged 65 years or older with newly diagnosed Parkinson's disease as the case group [mean age 75.0 years and standard deviation (SD) 5.0 years], and 15,416 patients without Parkinson's disease as the control group (mean age 74.0 years and SD 5.3 years). Multivariable logistic regression analysis detected no association between gout and Parkinson's disease in both sex [odds ratio (OR) = 0.98, 95% confidence interval (CI) = 0.86–1.12, in men and OR = 1.03, 95% CI = 0.88–1.21, in women, respectively]. We conclude that no association can be detected between gout and Parkinson's disease in older people in Taiwan.

The aim of this study was to explore the interaction between alcoholism and polypharmacy on the risk of falls in the elderly in Taiwan. A data set of 1 million randomly sampled National Health Insurance claims in Taiwan was used in our analysis, from which 3482 new cases of falls in 2000–2008 and 13928 randomly selected controls without falls, both aged ≥ 65 years, were identified for a case-control study. Polypharmacy was defined as the average daily use of five or more prescribed drugs. Relative risks were estimated by adjusted odds ratio (OR) and 95% confidence interval (CI) using a multivariate logistic regression analysis.In comparison with participants using one or no drugs without alcoholism, the OR increased from 1.15 (95% CI 1.01–1.32) for those using two to four drugs without alcoholism, to 1.27 (95% CI 1.10–1.47) for those using five or more drugs without alcoholism, up to 5.32 (95% CI 1.58–18.0) for those using two to four drugs with alcoholism, and as high as to 6.29 (95% CI 2.22–17.8) for those using five or more drugs with alcoholism. We conclude that polypharmacy may interact with alcoholism and further increases the risk of falls in the elderly.