Anticoagulation Therapy for Atrial Fibrillation in Patients With Alzheimer's Disease.

Background and Purpose- Direct oral anticoagulants (DOACs) are safer, at least equally efficacious, and cost-effective compared to warfarin for stroke prevention in atrial fibrillation (AF) but they remain underused, particularly in demented patients. We estimated the cost-effectiveness of DOACs compared with warfarin in patients with AF and Alzheimer's disease (AD). Methods- We constructed a microsimulation model to estimate the lifetime costs, quality-adjusted life-years (QALYs), and cost-effectiveness of anticoagulation therapy (adjusted-dose warfarin and various DOACs) in 70-year-old patients with AF and AD from a US societal perspective. We stratified patient cohorts based on stage of AD and care setting. Model parameters were estimated from secondary sources. Health benefits were measured in the number of acute health events, life-years, and QALYs gained. We classified alternatives as cost-effective using a willingness-to-pay threshold of $100 000 per QALY gained. Results- For patients with AF and AD, compared with warfarin, DOACs increase costs but also increase QALYs by reducing the risk of stroke. For mild-AD patients living in the community, edoxaban increased lifetime costs by $6603 and increased QALYs by 0.076 compared to warfarin, yielding an incremental cost-effectiveness ratio of $86 882/QALY gained. Even though DOACs increased QALYs compared with warfarin for all patient groups (ranging from 0.019 to 0.085 additional QALYs), no DOAC treatment alternative had an incremental cost-effectiveness ratio <$150 000/QALY gained for patients with moderate to severe AD. For patients living in a long-term care facility with mild AD, the DOAC with the lowest incremental cost-effectiveness ratio (rivaroxaban) costs $150 169 per QALY gained; for patients with more severe AD, the incremental cost-effectiveness ratios were higher. Conclusions- For patients with AF and mild AD living in the community, edoxaban is cost-effective compared with warfarin. Even though patients with moderate and severe AD living in the community and patients with any stage of AD living in a long-term care setting may obtain positive clinical benefits from anticoagulation treatment, DOACs are not cost-effective compared with warfarin for these populations. Compared to aspirin, no oral anticoagulation (warfarin or any DOAC) is cost effective in patients with AF and AD.

Antibacterial activity of epigallocatechin-3-gallate (EGCG) and its synergism with ß-lactam antibiotics sensitizing carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

BACKGROUND: Infections caused by Acinetobacter baumannii were responsive to conventional antibiotic therapy. However, recently, carbapenem-associated multidrug resistant isolates have been reported worldwide and present a major therapeutic challenge. Epigallocatechin-3-Gallate (EGCG) extracted from green tea exhibits antibacterial activity. PURPOSE: We evaluated the antibacterial activity of EGCG and possible synergism with antibiotics in carbapenem-associated multidrug resistant A. baumannii. A potential mechanism for synergism was also explored. MATERIALS AND METHODS: Seventy clinical isolates of A. baumannii collected from geographically different areas were analyzed by minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EGCG. Checkerboard and time-killing assays were performed to exam the synergism between EGCG and antibiotics. The effects of EGCG on a multidrug efflux pump inhibitor (1-[1-naphthylmethyl] piperazine; NMP) and ß-lactamase production were also examined in A. baumannii. RESULTS: Sixty-three of 70 clinical isolates of A. baumannii carried carbapenemase-encoding genes with carbapenem-associated multidrug resistance. Levels of MIC and MBC of EGCG ranged from 64 to 512µg/ml and from 128 to ≥1024µg/ml, respectively among the clinical isolates. MIC90 and MBC86 levels were 256µg/ml and 512µg/ml of EGCG, respectively. Subinhibitory concentration of EGCG in combination with all antibiotics tested, including carbapenem, sensitized (MICs fall≤1.0µg/ml) all carbapenem-associated multidrug resistant isolates. Checkerboard and time-killing assays showed synergism between EGCG and meropenem (or carbenicillin) counted as fractional inhibitory concentration of < 0.5 and cell numbers' decrease per ml of >2log10 within 12h, respectively. EGCG significantly increased the effect of NMP but was unrelated to ß-lactamase production in A. baumannii, suggesting EGCG may be associated with inhibition of efflux pumps. CONCLUSION: Overall we suggest that EGCG-antibiotic combinations might provide an alternative approach to treat infections with A. baumannii regardless of antibiotic resistance.

Chemical properties, mode of action, and in vivo anti-herpes activities of a lignin-carbohydrate complex from Prunella vulgaris.

The chemical nature, the mode of action, and the in vitro and in vivo anti-HSV activities of the polysaccharide from Prunella vulgaris were characterized. The polysaccharide was isolated by ethanol precipitation, dialysis, CTAB precipitation, and gel exclusion chromatography. The isolated compound (PPS-2b) was a lignin-carbohydrate complex with a molecular weight of 8500. The carbohydrate moiety was composed of glucose, galactose, mannose, galacturonic acid, rhamnose, xylose, and arabinose with glucose as the major sugar. In plaque reduction assay, PPS-2b showed activities against HSV-1 and HSV-2. The anti-HSV activity could be abolished by periodate oxidation. Mechanism studies showed that PPS-2b inactivated HSV-1 directly, blocked HSV-1 binding to Vero cells, and inhibited HSV-1 penetration into Vero cells. A similar inhibition was observed with a gC-deficient strain of HSV-1. The in vivo activities of a Prunella cream formulated with a semi-purified fraction was assessed in a HSV-1 skin lesion model in guinea pigs and a HSV-2 genital infection model in BALB/c mice. Guinea pigs that received the Prunella cream treatment showed a significant reduction (P<0.01) in skin lesions. Mice that received the Prunella cream treatment showed a significant reduction (P<0.01) in mortality. In conclusion, the anti-HSV compound from P. vulgaris is a lignin-polysaccharide complex with potent activity against HSV-1 and HSV-2. Its mode of action appears to be inhibiting viral binding and penetration into host cells.

Uncinoside A and B, two new antiviral chromone glycosides from Selaginella uncinata.

Five compounds have been isolated from the dried whole plants of Selaginella uncinata, two of them were new chromone glycosides, 5-hydroxy-2,6,8-trimethylchromone 7-O-beta-D-glucopyranoside (uncinoside A) and 5-acetoxyl-2,6,8-trimethylchromone 7-O-beta-D-glucopyranoside (uncinoside B). Their structures were elucidated by spectroscopic methods including one- and two-dimensional NMR techniques. The other three compounds were identified as 8-methyl eugenitol, amentoflavone and hinokiflavone. Uncinoside A and B showed potent antiviral activities against respiratory syncytial virus (RSV) with IC(50) value of 6.9 and 1.3 microg/ml, moderate antiviral activities against parainfluenza type 3 virus (PIV 3) with IC(50) value of 13.8 and 20.8 microg/ml, respectively.

Antiviral Chinese medicinal herbs against respiratory syncytial virus.

Forty-four medicinal herbs were tested for antiviral activities against respiratory syncytial virus (RSV) by means of the cytopathologic effect (CPE) assay. Twenty-seven of the 44 medicinal herbs showed potent or moderate antiviral activities against RSV with 50% inhibition concentration (IC(50)) ranging from 6.3 to 52.1 microg/ml, and with selectivity index (SI) ranging from 2.0 to 32.1. Further purification of the active extracts from Sophora flavescens Ait. and Scutellaria baicalensis Georgi led to the identification of anagyrine (2), oxymatrine (7), sophoranol (10), wogonin (12), and oroxylin A (13) as the potent anti-RSV components.