Association Between Statin Use and the Incidence of Clinically Diagnosed Osteoarthritis: A Nationwide Retrospective Cohort Study in Taiwan.

OBJECTIVE: To investigate the effect of higher cumulative defined daily dose per year (cDDD/y) compared with lower cDDD/y of statin use in the incidence of any joint osteoarthritis (OA). DESIGN: In this population-based retrospective cohort study, patients who were aged ≥40 years were newly initiated on statin therapy between 2002 and 2011, and had a statin prescription for ≥90 days in the first year of treatment were identified from the 2000 Longitudinal Generation Tracking Database. All patients were separated into groups with higher cDDD/y (>120 cDDD/y) and lower cDDD/y (≤120 cDDD/y; as an active comparator) values. Propensity score matching was performed to balance potential confounders. All recruited patients were followed up for 8 years. Marginal Cox proportional hazard models were used to estimate time-to-event outcomes of OA. RESULTS: Compared with lower cDDD/y use, higher cDDD/y use did not reduce the risk of any joint OA (adjusted hazard ratio, 1.07; 95% confidence interval, 0.99-1.14). Dose-related analysis did not reveal any dose-dependent association. A series of sensitivity analyses showed similar results. Joint-specific analyses revealed that statin did not reduce the incidence of knee, hand, hip, and weight-bearing (knee or hip) OA. CONCLUSIONS: Higher cDDD/y statin use did not reduce the risk of OA in this Taiwanese nationwide cohort study. The complexity of OA pathogenesis might contribute to the ineffectiveness of statin. Repurposing statin with its anti-inflammation properties might be ineffective for OA development, and balancing the catabolism and anabolism of cartilage might be a major strategy for OA prevention.

Association between antihyperlipidemic agents and the risk of chronic periodontitis in patients with hyperlipidemia: A population-based retrospective cohort study in Taiwan.

BACKGROUND: The lipid-lowering and anti-inflammatory effects of statins and fibrates may ameliorate periodontitis. Patients with hyperlipidemia tend to have a worse periodontal status. This study assessed the association between the use of statins/fibrates and the incidence of chronic periodontitis in patients with hyperlipidemia in Taiwan. METHODS: This retrospective cohort study enrolled patients newly diagnosed with hyperlipidemia between 2001 and 2012 from the 2000 Longitudinal Generation Tracking Database and followed them for 5 years. The study population was divided into four groups: statin monotherapy, fibrate monotherapy, combination therapy (both statins and fibrates), and control (neither statins nor fibrates). Each patient in the treatment group was matched at a ratio of 1:1 with a control. Chronic periodontitis risk was compared in the three study arms by using a Cox proportional hazard model. RESULTS: Chronic periodontitis risk was reduced by 25.7% in the combination therapy group compared with the control group (adjusted hazard ratio [aHR], 0.743; 95% confidence interval (CI), 0.678-0.815). Low dose (<360 cumulative defined daily dose [cDDD]) and shorter duration (<2 years) of statin monotherapy seem to be associated with an increased risk of chronic periodontitis; high dose (≥720 cDDD/≥1080 cDDD) and longer duration (≥3 years) of statin/fibrate monotherapy may be correlated with a lower risk of periodontitis. Hydrophobic statin users had a lower chronic periodontitis risk than hydrophilic statin users. CONCLUSION: Chronic periodontitis risk was lower in patients with hyperlipidemia on combination treatment with statins and fibrates, and the risk decreased when patients used statins or fibrates for >3 years.

Association between Antihyperlipidemic Agent Use and Age-Related Macular Degeneration in Patients with Hyperlipidemia: A Population-Based Retrospective Cohort Study.

Several studies have indicated that lipoproteins might contribute to the pathogenesis of age-related macular degeneration (AMD). In this population-based retrospective cohort study, patients with hyperlipidemia were divided into two groups (study groups I and II) based on whether or not they were receiving antihyperlipidemic agents. The comparison group included patients without hyperlipidemia who were randomly selected and matched with study group II patients. A Cox proportional hazard model was used to evaluate the risk of AMD among the groups. Patients with hyperlipidemia receiving antihyperlipidemic agents (study group I, n = 15,482) had a significantly increased AMD risk (adjusted hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.04-1.45) compared to those not receiving antihyperlipidemic agents (study group II, n = 15,482). However, with an increase in cumulative exposure, a reduced risk of AMD was observed in patients using a defined daily dose of more than 721, with an adjusted HR of 0.34 (95% CI = 0.22-0.53, p < 0.001). Additionally, the adjusted HR of AMD for study group II was 1.40 (95% CI = 1.20-1.63, p < 0.001) relative to the comparison group (n = 61,928). In conclusion, the study results indicated that patients with hyperlipidemia have a higher AMD risk than patients without hyperlipidemia. Furthermore, patients with hyperlipidemia who received antihyperlipidemic agents had a significantly increased AMD risk. However, a dose-dependent reduction in the risk of AMD was observed in patients with hyperlipidemia using statins or/and fibrates.

Rapid identification of carbapenem-resistant Klebsiella pneumoniae based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry and an artificial neural network model.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a clinically critical pathogen that causes severe infection. Due to improper antibiotic administration, the prevalence of CRKP infection has been increasing considerably. In recent years, the utilization of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has enabled the identification of bacterial isolates at the families and species level. Moreover, machine learning (ML) classifiers based on MALDI-TOF MS have been recently considered a novel method to detect clinical antimicrobial-resistant pathogens. METHODS: A total of 2683 isolates (369 CRKP cases and 2314 carbapenem-susceptible Klebsiella pneumoniae [CSKP]) collected in the clinical laboratories of Taipei Medical University Hospital (TMUH) were included in this study, and 80% of data was split into the training data set that were submitted for the ML model. The remaining 20% of data was used as the independent data set for external validation. In this study, we established an artificial neural network (ANN) model to analyze all potential peaks on mass spectrum simultaneously. RESULTS: Our artificial neural network model for detecting CRKP isolates showed the best performance of area under the receiver operating characteristic curve (AUROC = 0.91) and of area under precision-recall curve (AUPRC = 0.90). Furthermore, we proposed the top 15 potential biomarkers in probable CRKP isolates at 2480, 4967, 12,362, 12,506, 12,855, 14,790, 15,730, 16,176, 16,218, 16,758, 16,919, 17,091, 18,142, 18,998, and 19,095 Da. CONCLUSIONS: Compared with the prior MALDI-TOF and machine learning studies of CRKP, the amount of data in our study was more sufficient and allowing us to conduct external validation. With better generalization abilities, our artificial neural network model can serve as a reliable screening tool for CRKP isolates in clinical practice. Integrating our model into the current workflow of clinical laboratories can assist the rapid identification of CRKP before the completion of traditional antimicrobial susceptibility testing. The combination of MADLI-TOF MS and machine learning techniques can support physicians in selecting suitable antibiotics, which has the potential to enhance the patients' outcomes and lower the prevalence of antimicrobial resistance.

Association between statin use and the risk of gout in patients with hyperlipidemia: A population-based cohort study.

Objective: To investigate the association between statin use and risk of gout in patients with hyperlipidemia. Methods: In this population-based retrospective cohort study, patients ≥20 years and diagnosed as having incident hyperlipidemia between 2001 and 2012 were identified from the 2000 Longitudinal Generation Tracking Database in Taiwan. Regular statin users (incident statin use, having 2 times and ≥90 days of prescription for the first year) and two active comparators [irregular statin use and other lipid-lowering agent (OLLA) use] were compared; the patients were followed up until the end of 2017. Propensity score matching was applied to balance potential confounders. Time-to-event outcomes of gout and dose- and duration-related associations were estimated using marginal Cox proportional hazard models. Results: Regular statin use non-significantly reduced gout risk compared with irregular statin use (aHR, 0.95; 95% CI, 0.90-1.01) and OLLA use (aHR, 0.94; 95% CI, 0.84-1.04). However, a protective effect was noted for a cumulative defined daily dose (cDDD) of >720 (aHR, 0.57; 95% CI, 0.47-0.69 compared with irregular statin use and aHR, 0.48; 95% CI, 0.34-0.67 compared with OLLA use) or a therapy duration of >3 years (aHR, 0.76; 95% CI, 0.64-0.90 compared with irregular statin use and aHR, 0.50; 95% CI, 0.37-0.68 compared with OLLA use). Dose- and duration-dependent associations were consistent in the 5-year sensitivity analyses. Conclusion: Although statin use was not associated with a reduction in gout risk, the protective benefit was observed in those receiving higher cumulative doses or with a longer therapy duration.

Association between GnRH analogue use and atopic diseases in patients with prostate cancer: A population-based retrospective cohort study.

PURPOSE: Gonadotropin-releasing hormone (GnRH) analogues reduce testosterone levels to castration levels in patients with prostate cancer. However, the role of testosterone in atopic diseases has remained undefined. We aimed to investigate this role. MATERIALS AND METHODS: This retrospective cohort study was conducted using the National Health Insurance Research Database (NHIRD). Patients with prostate cancer were categorized into two groups according to whether they received GnRH analogue treatment (study group I) or not (study group II), and men without prostate cancer and with no GnRH analogue use were defined to comprise the comparison group after their ages and index years were matched with group II. Cox proportional hazard models were used to assess the hazard ratio (HR) of atopic diseases. RESULTS: Group I, group II, and the comparison group comprised 663, 2,172, and 8,688 individuals, respectively. Group I had a significantly lower risk of atopic diseases (adjusted HR: 0.66, 95% CI, 0.49-0.89, p < 0.01) than did group II. A reduced risk of atopic diseases was found when GnRH analogues were prescribed for 2 months (adjusted HR 0.53, 95% CI, 0.29-0.97, p = 0.04) and 2-14 months (adjusted HR 0.66, 95% CI, 0.49-0.89, p = 0.007). No significant difference in the risk of atopic diseases between group II and the comparison group was observed. CONCLUSIONS: A decreased risk of atopic diseases was observed in patients with prostate cancer treated with GnRH analogues. Further studies are warranted to verify the association between testosterone levels and atopic diseases.

Use of gastric acid-suppressive agents increases the risk of dementia in patients with upper gastrointestinal disease: A population-based retrospective cohort study.

BACKGROUND: Prescriptions for gastric acid-suppressive agents, including proton-pump inhibitors (PPIs) and histamine type-2 receptor antagonists (H2RAs), are rising. However, little data exist regarding their association with dementia in the Asian population. The objective of this study was thus to investigate the impact of the use of PPIs and H2RAs on the risk of dementia in an Asian population with upper gastrointestinal disease (UGID). METHODS: We conducted a population-based retrospective cohort study with a 10-year follow-up using data from 2000 to 2015 derived from Taiwan's Longitudinal Health Insurance Database. We included 6711 patients with UGID receiving gastric acid-suppressive agents, 6711 patients with UGID not receiving agents, and 6711 patients without UGID or treatment thereof, all at least 20 years of age. Groups were matched for age, sex, and index date. The association between gastric acid-suppressive agent use and dementia was analyzed using a Cox proportional hazards regression model adjusted for potential confounders. RESULTS: The adjusted hazard ratio (aHR) of dementia for patients with UGID receiving gastric acid-suppressive agents compared with patients with UGID without gastric acid-suppressive agents was 1.470 (95% confidence interval [CI] 1.267-1.705, p < 0.001). Both PPIs and H2RAs increase the risk of dementia (PPIs: aHR 1.886 [95% CI 1.377-2.582], p < 0.001; H2RAs: aHR 1.357 [95% CI 1.098-1.678], p < 0.01), with PPIs exhibiting significantly greater risk (aHR 1.456 [95% CI 1.022-2.075], p < 0.05). CONCLUSIONS: Our results demonstrate an increased risk of dementia in patients with UGID receiving gastric acid-suppressive agents, including PPIs and H2RAs, and the use of PPIs was associated with a significantly greater risk than H2RA use.

Proteomic analysis of retinal pigment epithelium cells after exposure to UVA radiation.

BACKGROUND: Age-related macular degeneration (AMD) is the primary cause of blindness and severe vision loss in developed countries and is responsible for 8.7% of blindness globally. Ultraviolet radiation can induce DNA breakdown, produce reactive oxygen species, and has been implicated as a risk factor for AMD. This study investigated the effects of UVA radiation on Human retinal pigment epithelial cell (ARPE-19) growth and protein expression. METHODS: ARPE-19 cells were irradiated with a UVA lamp at different doses (5, 10, 20, 30 and 40 J/cm2) from 10 cm. Cell viability was determined by MTT assay. Visual inspection was first achieved with inverted light microscopy and then the DeadEnd™ Fluorometric TUNEL System was used to observe nuclear DNA fragmentation. Flow cytometry based-Annexin V-FITC/PI double-staining was used to further quantify cellular viability. Mitochondrial membrane potential was assessed with JC-1 staining. 2D electrophoresis maps of exposed cells were compared to nonexposed cells and gel images analyzed with PDQuest 2-D Analysis Software. Spots with greater than a 1.5-fold difference were selected for LC-MS/MS analysis and some confirmed by western blot. We further investigated whether caspase activation, apoptotic-related mitochondrial proteins, and regulators of ER stress sensors were involved in UVA-induced apoptosis. RESULTS: We detected 29 differentially expressed proteins (9 up-regulated and 20 down-regulated) in the exposed cells. Some of these proteins such as CALR, GRP78, NPM, Hsp27, PDI, ATP synthase subunit alpha, PRDX1, and GAPDH are associated with anti-proliferation, induction of apoptosis, and oxidative-stress protection. We also detected altered protein expression levels among caspases (caspase 3 and 9) and in the mitochondrial (cytosolic cytochrome C, AIF, Mcl-1, Bcl-2, Bcl-xl, Bax, Bad, and p-Bad) and ER stress-related (p-PERK, p-eIF2α, ATF4 and CHOP) apoptotic pathways. CONCLUSIONS: UVA irradiation suppressed the proliferation of ARPE-19 cells in a dose-dependent manner, caused quantitative loses in transmembrane potential (ΔΨm), and induced both early and late apoptosis.

Increased risk of periodontitis among patients with Crohn's disease: a population-based matched-cohort study.

BACKGROUND: Periodontitis is a frequently cited extraintestinal manifestation of Crohn's disease (CD). Despite a plethora of investigations and a recent meta-analysis linking CD and periodontitis, no study has estimated the risk of periodontitis among CD patients with respect to a comparison group nor has any investigation analyzed the effect of CD-specific medications on the risk of periodontitis. The present cohort study compared CD patients and matched subjects without a history of inflammatory bowel disease (IBD) to estimate the effect of CD and CD-specific pharmaceutical prescriptions on the risk of developing periodontitis by leveraging a population-based dataset in Taiwan. METHODS: We sourced 6657 CD patients and 26,628 comparison subjects without a history of IBD from the Taiwan National Health Insurance Database. Cox proportional hazards regressions were used to estimate the risk of subsequent periodontitis by CD status and pharmaceutical prescription during the follow-up period. RESULTS: After adjusting for socioeconomic status (SES), urbanicity, selected medical co-morbidities, and CD-specific pharmaceutical prescriptions, the hazard ratio (HR) for subsequent periodontitis among patients with CD was 1.36 (95% CI = 1.25-1.48) that of comparison subjects. There was not a significant difference in risk between genders or across ages. Steroids (95% CI = 0.66-0.77) appeared to confer a protective effect and Aspirin, Plavix, and Licodin were marginally protective (95% CI = 0.76-0.95). CONCLUSION: This is the first study to report an increased HR for subsequent periodontitis among CD patients when compared to matched comparison subjects without IBD. The protective effect of some pharmaceuticals may suggest that treatment of CD protects against periodontitis.

Influence of Socioeconomic Factors, Gender and Indigenous Status on Smoking in Taiwan.

The indigenous Austronesian minority of Taiwan is heavily affected by health disparities which may include suffering from a greater burden of the tobacco epidemic. While a lack of representative data has historically precluded an investigation of the differences in smoking between Taiwanese ethnicities, these data have recently become available through an annual population-based telephone survey conducted by the Health Promotion Administration, Ministry of Health and Welfare (previously known as the Bureau of Health Promotion (BHP), Department of Health). We used the BHP monitoring data to observe the prevalence of smoking and environmental tobacco smoke exposure among indigenous and non-indigenous Taiwanese surrounding a tobacco welfare tax increase in 2006, investigate ethnic differences in smoking prevalence and environmental tobacco smoke exposure each year between 2005 and 2008, and perform multiple logistic regression to estimate measures of association between potential risk factors and smoking status. Despite significant ethnic and gender differences in smoking prevalence, smoking status was not found to be significantly associated with ethnicity after controlling for socioeconomic and demographic factors.

Increased risk of stroke among patients with Crohn's disease: a population-based matched cohort study.

BACKGROUND: Crohn's disease (CD) is one type of inflammatory bowel disease (IBD) that has been speculated to share prognostic factors with the development of stroke. There is controversial information in the literature regarding the association between CD and stroke. The present cohort study estimated the risk of subsequent stroke among CD patients compared with matched comparison subjects drawn from a population-based dataset in Taiwan. METHOD: This study drew data from the Taiwan National Health Insurance Database to conduct a historical cohort study. The study cohort comprised 3309 CD patients, and the comparison cohort comprised 13,236 subjects without an IBD. Cox proportional hazards regressions were performed to estimate the risk of subsequent stroke during the follow-up period. We also conducted additional analyses stratifying by age group and gender. RESULTS: After adjusting for selected medical co-morbidities and recent prescriptions of selected pharmaceuticals, the hazard ratio (HR) for subsequent stroke among patients with CD was found to be 1.911 (95% confidence interval (CI) = 1.65-2.22) that of comparison subjects. While we did not detect an association between stroke and CD among patients aged 30-40 years, we did detect increased risks for stroke among CD patients aged 40-50 years (HR = 2.29) and those aged over 50 years (HR = 1.88). We also found women (HR = 2.39) to be at a greater risk than men (HR = 1.50). CONCLUSION: This study reports an increased HR for subsequent stroke among CD patients when compared to matched comparison patients without IBD in an Asian population.

Gender differences in recreational sports participation among Taiwanese adults.

This study examines the gender differences in the enjoyment of recreational sports participation among Taiwanese adults. Data were obtained using the 2007 Taiwan Social Change Survey. The questionnaire included a topical module of the International Social Survey Program regarding leisure time and sports. Results showed that male subjects were more likely to participate in recreational sports to improve their appearance and on account of their personal interest. In addition to these factors, female subjects also experienced greater motivation to participate when Taiwanese athletes performed well in international sporting competitions. This study confirmed that the factors influencing enjoyment of recreational sports participation differ among men and women. These results can be used to better inform public health professionals and other regulatory organizations formulating physical activity intervention strategies.