Evaluation of the timing of using direct oral anticoagulants after ischemic stroke for patients with atrial fibrillation.

Background and objective: Patients with atrial fibrillation (AF) are prescribed oral anticoagulants for stroke prevention; however, no evidence indicates that the use of direct oral anticoagulants (DOACs) in the first few days after ischemic stroke (IS) would result in favorable outcomes. This study evaluated the association between the timing of using DOACs after IS and their effectiveness and safety to determine the optimal timing. Methods: In this retrospective cohort study, we reviewed the electronic medical records of Taipei Veterans General Hospital. The 1-year outcomes of patients after DOAC initiation were evaluated. Different initiation time windows were compared (initiation time ≤3 days and >3 days in primary analysis). The primary composite outcome was stroke, transient ischemic attack, systemic embolism, or death due to IS. The primary safety outcome was major bleeding or clinically relevant nonmajor bleeding. The secondary composite outcome was all-cause mortality, thromboembolic event, or acute myocardial infarction/hemorrhagic events. Results: This study included 570 patients. The median initiation time of DOACs after IS in the patients with AF was 14 days. Compared the patients in whom DOACs were initiated after >3 days with those DOACs were initiated after ≤3 days, the adjusted hazard ratios (aHRs) of the primary composite outcome was 0.73 (95% confidence interval [CI]: 0.23-1.79), the aHR of primary safety outcome was 0.87 (95% CI: 0.34-1.90), and the aHR of secondary composite outcome was 0.65 (95% CI: 0.32-1.19). All the results were not statistically significant. In secondary analysis, we tested multiple time points of initiating DOACs. Compared with DOAC initiation after >14 days, the primary composite outcomes in the patients in whom DOACs were initiated ≤3, 4-7, and 8-14 days after IS were the same as the findings of the main analysis. After separating patients into different stroke severity groups, the results were similar to those in the main analysis. Conclusion: No significant association was observed between the timing of using DOACs and ischemic or hemorrhagic outcomes. The findings did not differ among different time points. Although we do not recommend avoiding the initiation of DOACs in the first few days after IS, we should consider that the early initiation of DOACs (≤3 days) would be appropriate only for patients who tend to experience thromboembolic events and have a low risk of bleeding. The optimal timing of initiation still must be confirmed by randomized controlled trials.

Consumption of vitamin D2 enhanced mushrooms is associated with improved bone health.

Mushrooms are the best nonanimal food source of vitamin D2. Pulsed irradiation can enhance vitamin D2 in mushrooms quickly. We investigated the effect of supplementing high vitamin D2Pleurotus ferulae mushrooms in a mouse model of osteoporosis. Thirty-two female C57BL/6JNarl mice were divided into four groups including sham, ovariectomized (OVX), OVX+nonpulsed mushroom (NPM) and OVX+pulsed mushroom (PM). After 23 weeks of treatment, serum samples were analyzed for osteoblast and osteoclast indicators, as well as metabolites using NMR spectroscopy. To examine bone density, femurs were analyzed using micro-computed tomography. The NPM and PM treatment mice showed increased bone density in comparison with OVX mice. In addition, the PM mice showed higher osteoblast and lower osteoclast indicators in comparison with OVX mice. Serum metabolomics analysis indicated several metabolites that were different in PM mice, some of which could be correlated with bone health. Taken together, these results suggest that pulsed irradiated mushrooms are able to increase bone density in osteoporotic mice possibly through enhanced bone metabolism. Further studies in humans are needed to show their efficacy in preventing osteoporosis.

An NMR metabolomic study on the effect of alendronate in ovariectomized mice.

Alendronate sodium (Fosamax) is most widely used for the prevention and treatment of osteoporosis. It is a type of anti-resorptive agent that reduces the risk of fractures by changing bone turnover and bone mineral density. We investigated the effect of Fosamax on a mouse model of osteoporosis. Twenty-seven female C57BL/6JNarl mice were divided into three groups: sham, ovariectomized (OVX) and OVX + Fosamax (Fosamax). After 23 weeks, bone density of femurs was analyzed using microcomputed tomography (micro-CT), and serum was analyzed for osteoblast and osteoclast activity, as well as metabolites using nuclear magnetic resonance (NMR) spectroscopy. Fosamax increased bone mineral density and cortical bone thickness, and decreased osteoblast activity slightly. Fosamax did not significantly change osteoclast activity. Serum metabolomics revealed that Fosamax had profound effects on overall metabolism, as significantly higher concentrations of metabolites associated with energy metabolism (including TCA-cycle intermediates and glucose), 3-hydroxybutyrate, taurine, allantoin, acetate, and ethanol, as well as lower concentrations of aspartate were observed in the Fosamax-treated mice compared with the OVX mice. These results suggest that alendronate may work by increasing bone density through altered metabolic activity.

Chemical composition and nutritional and medicinal value of fruit bodies and submerged cultured mycelia of culinary-medicinal higher Basidiomycetes mushrooms.

This research gives the results of a proximate analysis (moisture, ash, crude protein, fat, total carbohydrates, and total energy); a bioactive compounds analysis (γ-aminobutyric acid [GABA], ergothioneine, lovastatin, and cordycepin); fatty acid and amino acid analysis; and an analysis of macro- and microelement content of fruit bodies and mycelia of 15 higher Basidiomycetes medicinal mushroom strains belonging to 12 species. The results obtained demonstrate that almost all investigated mushrooms were found to be good sources of proteins and carbohydrates, with content varying in the ranges of 8.6-42.5% and 42.9-83.6%, respectively. Different species exhibited distinct free amino acid profiles. The total amino acid content was highest in Ophiocordyceps sinensis (MB) (23.84 mg/g) and Cordyceps militaris (FB) (23.69 mg/g). The quantification of the identified fatty acids indicated that, in general, palmitic acid, oleic acid, stearic acid, and linoleic acid were the major fatty acids. The micro- and macroelement compositions were studied, and the highest results were (as milligrams per kilogram) 224-7307 for calcium, 1668-38564 for potassium, 1091-11676 for phosphorus, and 5-97 for zinc. Bioactive components were lovastatin, GABA, and ergothioneine, which are commonly found in most mushrooms. C. militaris (FB), Pleurotus ostreatus (FB), and Coprinus comatus (FB) were most abundant and contained a high amount of GABA (756.30 µg/g, 1304.99 µg/g, 1092.45 µg/g, respectively) and ergothioneine (409.88 µg/g, 2443.53 µg/g, 764.35 µg/g, respectively). The highest lovastatin content was observed in Hericium erinaceus (FB) (14.38 µg/g) and Ganoderma lucidum (FB) (11.54 µg/g). In contrast to C. militaris (FB), cordycepin was not detected in O. sinensis (MB). The fruit body biomass of C. militaris cordycepin content reached 1.743 mg/g dry weight. The nutritional values of the mushroom species studied here could potentially be used in well-balanced diets and as sources of bioactive compounds.

Effectiveness of 2 rotavirus vaccines against rotavirus disease in Taiwanese infants.

BACKGROUND: Two rotavirus (RV) vaccines (Rotarix and RotaTeq) are available on the private market in Taiwan, but are not recommended for routine use. We examined RV vaccine effectiveness (VE) against severe RV acute gastroenteritis (AGE) among Taiwanese infants to inform policymakers on the potential benefits of national RV vaccine introduction. METHODS: From May 2009 to April 2011, a case-control assessment of VE against severe RV AGE was conducted at 3 hospital-based surveillance sites in Taiwan. Case-patients included children aged 8-35 months, hospitalized with laboratory-confirmed RV AGE. Controls included children age-matched within 1 month of age of the case-patient, hospitalized with RV-negative AGE or seen for non-AGE illnesses at the same hospitals. Vaccination history was confirmed through vaccination card or hospital record review. VE was calculated as (1--odds ratio of vaccination) × 100%. RESULTS: We enrolled 184 case-patients with RV AGE, 904 RV-negative AGE and 909 non-AGE controls. Two-dose Rotarix series VE against RV gastroenteritis hospitalization was 90.4% [95% confidence interval (CI): 70.3%, 98.1%) and 92.5% (95% CI: 77.1%, 98.5%) with RV-negative AGE and non-AGE controls, respectively. Three-dose RotaTeq series VE was 96.8% (95% CI: 82.3%, 100%) and 97.1% (95% CI: 84%, 100%) with RV-negative AGE and non-AGE controls, respectively. CONCLUSIONS: Both vaccines provided excellent protection against severe RV AGE hospitalization. Addition of RV vaccination into Taiwan's National Immunization Program could substantially decrease AGE hospitalizations among children <3 years. Our findings should help inform policymakers in Taiwan and other similar Asian countries when deciding whether to include RV vaccination into their national immunization programs.

Comparative study of contents of several bioactive components in fruiting bodies and mycelia of culinary-medicinal mushrooms.

Mushrooms (including fruiting bodies and mycelia) contain several bioactive components such as lovastatin, γ-aminobutyric acid (GABA), and ergothioneine. This article reports the results of 49 samples, including 9 fruiting bodies, 39 mycelia, and 1 vegetative cell, of 35 species of culinary-medicinal mushrooms from 18 genera: Agaricus, Agrocybe, Coprinus, Cordyceps, Cyathus, Daedalia, Flammulina, Fomes, Ganoderma, Grifola, Laetiporus, Lentinus, Morchella, Ophiocordyceps, Pleurotus, Trametes, Tremella, and Verpa. The results show that Cyathus striatus strain 978 contained the highest amount of lovastatin (995.66 mg/kg) in mycelia. Among fruiting bodies, 6 samples contained a high amount of GABA (274.86-822.45 mg/kg), whereas among mycelia, contents of GABA in 27 samples ranged from 215.36 to 2811.85 mg/kg. Among mycelia, Pleurotus cornucopiae strain 1101 contained the highest amount of ergothioneine (3482.09 mg/kg). Overall, these 3 bioactive components were commonly found in most mushrooms, and the results obtained might be related to their beneficial effects.

Increase of carbapenem-resistant Acinetobacter baumannii infection in acute care hospitals in Taiwan: association with hospital antimicrobial usage.

OBJECTIVE: Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as an important pathogen causing healthcare-associated infections (HAIs) in Taiwan. The present study is aimed to investigate the epidemiology of HAIs caused by CRAB and the association of CRAB infection and hospital usage of different antimicrobials. METHODS: Two nationwide databases in the period 2003 to 2008, the Taiwan Nosocomial Infection Surveillance System and National Health Insurance claim data, were used for analysis. A total of 13,811 healthcare-associated A. baumannii infections and antimicrobial usage data from 121 hospitals were analyzed. RESULTS: There was a significant increase in the proportion of number of HAIs caused by CRAB over that by all A. baumannii (CRABpAB), from 14% in 2003 to 46% in 2008 (P<0.0001). The greatest increase was in central Taiwan, from 4% in 2003 to 62% in 2008 (P<0.0001). Use of anti-pseudomonal carbapenems, but not other classes of antibiotics, was significantly correlated with the increase of CRABpAB (r = 0.86, P<0.0001). CONCLUSIONS: We suggested that dedicated use of anti-pseudomonal carbapenems would be an important intervention to control the increase of CRABpAB.

Re-examination of chromogenic quantitative assays for determining flavonoid content.

Flavonoids in plants have gained worldwide attention because of their benefits for human health. This study compared three analytical procedures commonly used for determining flavonoid content in plant samples in terms of chromogenic relationships and the reaction products of different flavonoid structures by means of using flavonoid standards with flavone, flavonol, flavanone, flavanol, and isoflavone and analytes such as phenolic acids commonly found in plant extracts. Procedure A produced a stable color reaction between 3-hydroxy-4-keto-flavonoids (flavonols) and 5-hydroxyflavones and was highly sensitive. Procedure B produced color reactions among most of the flavonoids, but the reaction products had different colors and faded over time. Procedure B also produced a color reaction with caffeic and chlorogenic acid. Procedure C was the most sensitive. It produced a color reaction and, like procedure A, could be used to quantify flavonols and 5-hydroxyflavones, but also showed color reaction toward caffeic and chlorogenic acid. On the basis of the results, the current three procedures are not satisfactory for determining all of the types of flavonoid. Two issues needed to be clarified before a promising determination of flavonoid content could be performed with chromogenic assays. The first is a survey of the literature to screen the possible predominant component of flavonoid in analytes. The other is guided by the predominant flavonoid; a promising calibration curve for flavonoid detection can be established on the basis of the selection of an appropriate method and a chemical standard with an equivalent dose response to the predominant flavonoid.

Usage of the claim database of national health insurance programme for analysis of cisapride-erythromycin co-medication in Taiwan.

PURPOSE: This study aimed to use the National Health Insurance Research Database, Taiwan for risk analysis of concomitant use of cisapride and erythromycin. METHODS: The sample consisted of subjects identified in the Outpatient Sampling Database (OSD) and Longitudinal Health Insurance Database 2000 (LHID 2000), derived from the original claim data of the National Health Insurance Research Database, Taiwan. RESULTS: According to the LHID 2000, a total of 464 individuals experienced 685 episodes of cisapride-erythromycin co-medication prescribed by 295 physicians, revealing a prevalence of 4.5% concomitant use, with higher prevalence in clinics (9.2%) than in other medical institutes (3.7-5.4%). Among the co-medication episodes, 81.9% and 61.2% were prescribed from the same health institutes and by the same physicians, respectively. No medical record of cardiac arrhythmias was found among these patients in 2001 and 2002, probably due to the fact that 78.9% of the 464 individuals were under age 16, 84.0% had short exposure duration (1-4 days) and 98.0% of the episodes were prescribed with a cisapride dose of less than 0.8 mg/kg/day. CONCLUSIONS: Findings from this study suggest that there exists an urgent need for accreditation in terms of pharmacovigilance of clinical sites and their practicing physicians for the prevention of irrational concomitant prescription in Taiwan. Our findings also indicate that it is necessary to investigate other possible conditions of potentially dangerous co-medication in Taiwan and other developing countries.

Changes before and after a policy to restrict antimicrobial usage in upper respiratory infections in Taiwan.

The Bureau of National Health Insurance (BNHI) of Taiwan issued a new reimbursement regulation effective from 1 February 2001 forbidding the use of antimicrobials in ambulatory patients with upper respiratory infections (URI) without evidence of bacterial infection. We evaluated the effect of this regulation by analysing changes in the types of infections diagnosed and the amount of antibiotics prescribed in 1999, 2000 and 2001. Between 1999 and 2001, antimicrobials for respiratory infections decreased from 18.0 to 9.97 DDD/1000 per day or by 44.6% (P=0.0000+). Antimicrobials for URI decreased from 8.32 in 1999 to 3.28 DDD/1000 per day in 2001 or by 60.6% (P=0.0000+); from 2000 to 2001 the decrease was 55.8%. Reduction of antimicrobials for URI from 1999 to 2001 accounted for 62.8% of the reduction of antimicrobials in respiratory infections or 51.3% of the total reduction of antimicrobials. Reduction in aminopenicillins was responsible for most of the decrease.

Antimicrobial usage in ambulatory patients with respiratory infections in Taiwan, 2001.

BACKGROUND AND PURPOSE: Excess use of antimicrobials by ambulatory patients is a determinant of antimicrobial resistance. This study investigated the types of illnesses for which antimicrobials were prescribed and the amounts prescribed with special emphasis on respiratory infections for the year in which the Bureau of National Health Insurance (BNHI) enforced a policy to restrict antimicrobials for upper respiratory infections. The number of ambulatory patients seen and the types of ambulatory facilities in Taiwan were also described. METHODS: Raw data were obtained from the BNHI database on every 500 th visit in 2001. Medical diagnoses were categorized according to the ICD-9-CM system. Antimicrobial consumption was expressed in defined daily doses per 1000 population per day (DDD/1000/day). RESULTS: Among the population of 22.3 million in Taiwan, there were 285.8 million ambulatory patient visits (12.8 per person), including 108.9 million visits (4.9 per person) for respiratory infections, of which 62.7 million (2.8 per person) were for upper respiratory infections (URI). Antimicrobial consumption was 19.83 DDD/1000/day [standard error (SE), 0.00055], of which 9.97 DDD/1000/day (SE, 0.00047) were for respiratory infections and 4.03 DDD/1000/day (0.00055) were for URI. 23.6% of visits for URI entailed a prescription for antimicrobials. About two-thirds (66.5%) of ambulatory patients were seen in clinics, mostly private ones, and 67.6% of all antimicrobials were received there. Aminopenicillins and cephalosporins constituted 35.2% and 19.5%, respectively, of antimicrobials prescribed. CONCLUSIONS: Despite the new BNHI rule restricting antimicrobial usage for URI, Taiwan still has an excessive number of ambulatory patient visits, especially for respiratory infections and URI. The majority of antimicrobials used were for URI. They were mostly prescribed in private clinics rather than hospital outpatient departments.