Identification of the perpetrator imperatorin in Xin-yi-san-theophylline interaction: observed and predicted herb-drug interaction in rats.

OBJECTIVES: Theophylline is a bronchodilator with a narrow therapeutic index and primarily metabolised by cytochrome P450 (CYP) 1A2. Xin-yi-san (XYS) is a herbal formula frequently used to ameliorate nasal inflammation. This study aimed to investigate the effects of XYS and its ingredient, imperatorin, on theophylline pharmacokinetics in rats. METHODS: The kinetics of XYS- and imperatorin-mediated inhibition of theophylline oxidation were determined. Pharmacokinetics of theophylline were analysed. Comparisons were made with the CYP1A2 inhibitor, fluvoxamine. KEY FINDINGS: XYS extract and its ingredient, imperatorin, non-competitively inhibited theophylline oxidation. Fluvoxamine (50 and 100 mg/kg) and XYS (0.5 and 0.9 g/kg) significantly prolonged the time to reach the maximum plasma concentration (tmax) of theophylline by 3-10 fold. In a dose-dependent manner, XYS and imperatorin (0.1-10 mg/kg) treatments significantly decreased theophylline clearance by 27-33% and 19-56%, respectively. XYS (0.9 g/kg) and imperatorin (10 mg/kg) significantly prolonged theophylline elimination half-life by 29% and 142%, respectively. Compared with the increase (51-112%) in the area under curve (AUC) of theophylline by fluvoxamine, the increase (27-57%) by XYS was moderate. CONCLUSIONS: XYS decreased theophylline clearance primarily through imperatorin-suppressed theophylline oxidation. Further human studies are essential for the dose adjustment in the co-medication regimen.

Factors Influencing the Use of Health Information Exchange by Physicians-Using the National Health Insurance PharmaCloud System in Taiwan.

This study aimed to investigate the factors influencing physicians use of the PharmaCloud system in Taiwan through Technology Continuance Theory (TCT) and to construct a TCT-based structured questionnaire to demonstrate the attitude and behavior of physicians in the Taiwanese medical system. It focused on investigating "confirmation", "perceived usefulness", "perceived ease of use", "attitude", "satisfaction", and "continuance intention" towards the preload-based comparison and manual search in PharmaCloud by attending physicians during their outpatient clinics. Path analysis was used to analyze the cause and effect relationship between variables. This study collected 528 valid questionnaires and the results of path analysis found that factors affecting physicians' continued use of preload-based comparison in PharmaCloud included "perceived usefulness", "satisfaction", and "attitude" (all p < 0.001); however, factors that influenced physicians' continued use of manual search in PharmaCloud were only "satisfaction" and "attitude" (all p < 0.001). Additionally, the effects of "perceived usefulness" and "perceived ease of use" on "satisfaction" could only be seen in preload-based comparison in PharmaCloud. In conclusion, when physicians' actual use of PharmaCloud met their expectations, physicians had higher levels of confirmation and better perceived usefulness, which naturally increased their satisfaction and attitude towards PharmaCloud and positively prompted them to continue using it.

In Vitro and In Vivo Evaluations of ß-Lactam/ß-Lactamase Mono- and Combined Therapies against Carbapenem-Nonsusceptible Enterobacteriaceae in Taiwan.

Increasing carbapenem resistance rates worldwide underscored the urgent need of novel antimicrobials. Ceftazidime-avibactam and aztreonam-avibactam combinations are developed to combat carbapenem resistance, but biological and geographic variations must be considered for antibiotic susceptibility patterns varied. Thus, we sought to assess the susceptibilities of ceftazidime-avibactam and aztreonam-avibactam against 660 carbapenem-nonsusceptible Enterobacteriaceae isolates (472 Klebsiella pneumoniae and 188 Escherichia coli) collected during an earlier Taiwan surveillance study. Agar dilution method was used to determine ceftazidime-avibactam and aztreonam-avibactam susceptibility. Metallo-carbapenemase's contribution to resistance were investigated with EDTA addition. The in vivo efficacies were evaluated using a Caenorhabditis elegans model. High susceptibility rates were observed for ceftazidime-avibactam and aztreonam-avibactam against the 472 carbapenem-nonsusceptible K. pneumoniae (CnsKP) (85.2% and 95.3%, respectively) and 188 carbapenem-nonsusceptible E. coli (CnsEC) isolates (91.5% and 94.1%, respectively). For non-metallo-carbapenemase producers, the susceptibility rates for ceftazidime-avibactam were 93.6% for CnsKP and 97.7% for CnsEC, whereas only 7.1% CnsKP and 11.1% CnsEC in metallo-carbapenemase producers were susceptible to ceftazidime-avibactam. Of all isolates, 95.3% CnsKP and 94.1% CnsEC were susceptible to aztreonam-avibactam. In C. elegans model, ceftazidime-avibactam and aztreonam-avibactam revealed effective against a blaKPC-producing K. pneumoniae isolate in vivo. Our results propose a positive therapeutic approach for both combinations against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.

Neovascular age-related macular degeneration is associated with cataract surgery.

PURPOSE: This retrospective cohort study examines the association between cataract surgery and neovascular age-related macular degeneration (AMD) during 5-year follow-up using population-based claims data. METHODS: We analysed data sourced from the Taiwan Longitudinal Health Insurance Database 2005. The study included 3465 patients who had undergone cataract operations and did not have a diagnosis of AMD before or on the surgery date (study group), and 10 395 age- and sex-matched comparison patients selected randomly from the remaining patients without an AMD diagnosis before the index date. We tracked the claims of each patient for a 5-year period to identify patients with a subsequent diagnosis of neovascular AMD. RESULTS: The incidence rate of neovascular AMD was 0.88 (95% confidence interval (CI): 0.66-1.14) per 1000 person-years among all sampled patients, 1.60 (95% CI: 1.04-2.36) among the cataract surgery patients and 0.64 (95% CI: 0.43-0.91) among comparison patients (p < 0.001). Stratified Cox proportional analysis showed that relative to the comparison cohort, the adjusted hazard ratio for neovascular AMD during 5-year follow-up was 2.68 (95% CI: 1.55-4.66) for patients who had undergone cataract operation. We censored those who died during follow-up period and adjusted for patients' monthly income, geographical location, urbanization level, diabetes, hypertension, cardiovascular disease and hyperlipidaemia. CONCLUSION: This study demonstrated epidemiological evidence of a link between cataract surgery and neovascular AMD during a 5-year follow-up period.

Incremental Healthcare Service Utilization for Open-angle Glaucoma: A Population-Based Study.

PURPOSE: To investigate differences in the utilization of healthcare services between subjects with open-angle glaucoma (OAG) and comparison subjects without OAG using Taiwan's National Health Insurance population-based database. PATIENTS AND METHODS: The study comprised 2204 subjects with OAG and 2204 sex-matched and age-matched subjects without OAG. We individually followed each subject for a 1-year period to evaluate their healthcare resource utilization. Outcome variables of the healthcare resource utilization were as follows: numbers of outpatient visits and inpatient days and the mean costs of outpatient and inpatient treatment. In addition, we divided healthcare resource utilization into ophthalmologic and nonophthalmologic services. RESULTS: As for the utilization of ophthalmologic services, OAG subjects had significantly more outpatient visits (7.4 vs. 1.3, P<0.001) and significantly higher outpatient costs (US$272 vs. US$39, P<0.001) than comparison subjects. For nonophthalmologic services, OAG subjects also had significantly more outpatient visits (29.4 vs. 21.8, P<0.001) and significantly higher outpatient costs (US$1263 vs. US$847, P<0.001) than comparison subjects. Furthermore, OAG subjects incurred significantly higher inpatient costs compared with comparison subjects (US$434 vs. US$234, P<0.001). For all healthcare services, OAG subjects had significantly more outpatient visits (36.8 vs. 23.1, P<0.001) and significantly higher outpatient (US$1535 vs. US$887, P<0.001) and total (US$2245 vs. US$1122, P<0.001) costs than comparison subjects. In other words, the total cost was about 2-fold greater for OAG subjects than comparison subjects. CONCLUSIONS: We concluded that subjects with OAG had significantly higher utilization of all healthcare services than comparison subjects.

Dementia is associated with iron-deficiency anemia in females: a population-based study.

Cognitive derangement and neurological symptoms are observed in patients with anemia. Although it is still controversial, a few studies suggested that anemia may increase the risk of dementia. This study aimed to explore the association between iron-deficiency anemia (IDA) and dementia in a population-based case-control study. We retrieved our study sample from the Taiwan Longitudinal Health Insurance Database 2000. We extracted 8300 subjects with a diagnosis of dementia and 8300 age- and gender-matched controls. The results showed that there was a significant difference in the prevalence of prior IDA between cases and controls (6.0% vs. 3.8%, p<0.001). The conditional logistic regression analysis suggested that the odds ratio (OR) of prior IDA for cases was 1.36 (95% CI: 1.07-1.74) compared to controls after adjusting for subjects' monthly income, geographic location, urbanization level, hyperlipidemia, diabetes, hypertension, and alcohol abuse. Among female subjects, the adjusted OR of prior IDA for cases was as high as 2.00 (95% CI: 1.42-2.80) compared to controls. However, in men-no increased odds of prior IDA were observed, compared to controls. We concluded that women with dementia had a higher prevalence of prior IDA, compared to controls.