Rates of hemorrhage during warfarin therapy for atrial fibrillation

Background:

Although warfarin has been extensively studied in clinical trials, little is known about rates of hemorrhage attributable to its use in routine clinical practice. Our objective was to examine incident hemorrhagic events in a large population-based cohort of patients with atrial fibrillation who were starting treatment with warfarin.

Methods:

We conducted a population-based cohort study involving residents of Ontario (age ≥ 66 yr) with atrial fibrillation who started taking warfarin between Apr. 1, 1997, and Mar. 31, 2008. We defined a major hemorrhage as any visit to hospital for hemorrage. We determined crude rates of hemorrhage during warfarin treatment, overall and stratified by CHADS₂ score (congestive heart failure, hypertension, age ≥ 75 yr, diabetes mellitus and prior stroke, transient ischemic attack or thromboembolism).

Results:

We included 125 195 patients with atrial fibrillation who started treatment with warfarin during the study period. Overall, the rate of hemorrhage was 3.8% (95% confidence interval [CI] 3.8%–3.9%) per person-year. The risk of major hemorrhage was highest during the first 30 days of treatment. During this period, rates of hemorrhage were 11.8% (95% CI 11.1%–12.5%) per person-year in all patients and 16.7% (95% CI 14.3%–19.4%) per person-year among patients with a CHADS₂ scores of 4 or greater. Over the 5-year follow-up, 10 840 patients (8.7%) visited the hospital for hemorrhage; of these patients, 1963 (18.1%) died in hospital or within 7 days of being discharged.

Interpretation:

In this large cohort of older patients with atrial fibrillation, we found that rates of hemorrhage are highest within the first 30 days of warfarin therapy. These rates are considerably higher than the rates of 1%–3% reported in randomized controlled trials of warfarin therapy. Our study provides timely estimates of warfarin-related adverse events that may be useful to clinicians, patients and policy-makers as new options for treatment become available.Atrial fibrillation is a major risk factor for stroke and systemic embolism, and strong evidence supports the use of the anticoagulant warfarin to reduce this risk.^1–3 However, warfarin has a narrow therapeutic range and requires regular monitoring of the international normalized ratio to optimize its effectiveness and minimize the risk of hemorrhage.^4,5 Although rates of major hemorrhage reported in trials of warfarin therapy typically range between 1% and 3% per person-year,^6–11 observational studies suggest that rates may be considerably higher when warfarin is prescribed outside of a clinical trial setting,^12–15 approaching 7% per person-year in some studies.^13–15 The different safety profiles derived from clinical trials and observational data may reflect the careful selection of patients, precise definitions of bleeding and close monitoring in the trial setting. Furthermore, although a few observational studies suggest that hemorrhage rates are higher than generally appreciated, these studies involve small numbers of patients who received care in specialized settings.^14–16 Consequently, the generalizability of their results to general practice may be limited.More information regarding hemorrhage rates during warfarin therapy is particularly important in light of the recent introduction of new oral anticoagulant agents such as dabigatran, rivaroxaban and apixaban, which may be associated with different outcome profiles.^17–19 There are currently no large studies offering real-world, population-based estimates of hemorrhage rates among patients taking warfarin, which are needed for future comparisons with new anticoagulant agents once they are widely used in routine clinical practice.²⁰We sought to describe the risk of incident hemorrhage in a large population-based cohort of patients with atrial fibrillation who had recently started warfarin therapy.     

Outbreak of acute respiratory disease caused by human adenovirus type 7 in a military training camp in Shaanxi,China

Outbreaks of ARD associated with HAdV have been reported in military populations in many countries. Here, we report an ARD outbreak caused by HAdV‐7 in a military training camp in Shaanxi Province, China, from February to March of 2012. Epidemic data and samples from the patients were collected, and viral nucleotides from samples and viral isolations were detected and sequenced. IgG and IgA antibodies against HAdV, and the neutralization antibodies against the viral strain isolated in this outbreak, were detected. Epidemiological study showed that all personnel affected were males with an average age of 19.1 years. Two peaks appeared on the epicurve and there was an 8‐day interval between peaks. Laboratory results of viral nucleotide detection carried out with clinical specimens were positive for HAdV (83.33%, 15/18). Further study through serum antibody assay, virus isolation and phylogenetic analysis showed that HAdV‐7 was the etiological agent responsible for the outbreak. IgA antibody began to appear on the 4th day after the onset and showed 100% positivity on the 8th day. The virus strain in the present outbreak was highly similar to the virus isolated in Hanzhong Shaanxi in 2009. We conclude that HAdV‐7 was the pathogen corresponding to the outbreak, and this is the first report of an ARD outbreak caused by HAdV‐7 in military persons in China. Vaccine development, as well as enhanced epidemiological and virological surveillance of HAdV infections in China should be emphasized.     

Cefotaxime prevents microbial contamination and improves microspore embryogenesis in wheat and triticale

Key message

Cefotaxime (100 mg/l) mitigate occasional gram negative bacterial contamination in wheat and triticale microspore culture and most importantly it increases cell growth and green plant production.

Abstract

Isolated microspore culture is a promising option to rapidly fix the product of meiotic recombination of F₁ hybrids, in the process of varietal development. Clean culture and high embryogenesis rate are essential to commercial triticale and wheat microspore cultures. So, this study investigated (1) contaminants from isolated microspores cultures, (2) two antibiotics to control bacterial growth, and (3) the contribution of antibiotics to increased microspore-derived embryo-like structures (ELS), green and albino plants. Five species of bacteria were identified in contaminated cultures (Erwinia aphidicola, Pantoea agglomerans, Pseudomonas sp., Staphylococcus epidermis and Staphylococcus warneri) using fatty acid analysis and 16S ribosomal RNA sequences analysis, and yeast. Antibacterial susceptibility test using Cefotaxime and Vancomycin resulted in strong inhibition of 24 bacterial isolates, using Cefotaxime at 100 mg/l, but not Pseudomonas sp. Other antibiotic treatments inhibited bacterial growth at least partially. Microspore induction medium supplemented with the same antibiotics treatments resulted in successful microspore embryogenesis and green plant production. Antibiotic treatments were first tested in triticale and then validated in wheat cultivars AC Carberry and AC Andrew. Induction medium supplemented with Cefotaxime at 50 and 100 mg/l substantially increased the formation of ELS and green plants in triticale and wheat, respectively. Incidentally, it also affected the occurrence of albinism in all genotypes. Our results demonstrated dual purpose of Cefotaxime for isolated microspore culture, most importantly it increases cell growth and success of microspore cultures in triticale and wheat genotypes, but would also prevent accidental loss of cultures with most common bacterial contaminants.     

Flow Karyotyping of Wheat Addition Line “T240” with a Haynaldia villosa 6VS Telosome

To construct a chromosome-specific DNA library of chromosome 6VS from Haynaldia villosa, a wheat alien chromosome addition line T240 with a 6VS chromosome arm and its parental common wheat cv. CA921 were used to optimize protocols for preparing chromosome suspension amenable to flow sorting of the 6VS chromosome. Our results showed that root tips incubated sequentially in Hogland’s solution containing 1.25 mM hydroxyurea (DNA synthesis inhibitor) for 18 h, a hydroxyurea-free period for 2 h, and 1 μM trifluralin for 4 h (metaphase blocking reagent) increased the metaphase index (MI) by up to 62 % . Many metaphase chromosomes were released to form a chromosome suspension when root tips fixed in 2 % paraformaldehyde were treated in a homogenizer at 9,500 rpm for 10–15 s. Most of the released chromosomes had intact morphology. The background solution of chromosome suspension was clear and relatively few of cell debris and chromosome clumps. Univariate flow karyotypes were established with chromosome suspension flow through FACS Vantage 2000 SE flow cytometer. The flow karyotype of CA921 consisted of four chromosome peaks, whereas that for T240 had a fifth peak. This fifth peak in T240 contained the telosome, which was further confirmed to be 6VS through fluorescence in situ hybridization.     

Fatty acid compositional changes during the embryonic development of the swimming crab,Portunus pelagicus (Portunidae: Decapoda)

Abstract

The fatty acid composition, moisture, and total lipid of the eggs from the swimming crab, Portunus pelagicus, at three different embryonic stages (within 24 h, during the eye placode stage and the final heart beat stage), were measured. Results showed that the moisture and lipid content significantly increased and decreased (p < 0.05), respectively, as the stages progressed. The most prevalent fatty acids that were initially deposited included C16:0, C18:1n-9, and C18:0, while the most consumed fatty acids were C22:5n-6, C22:5n-3, and C20:1n-7. Among the major fatty acid groups, polyunsaturated fatty acids (PUFA) and long-chain PUFA (LC-PUFA) were consumed more than saturated fatty acids and significantly more (p < 0.05) than monounsaturated fatty acids (p < 0.05). Meanwhile, n-3 PUFA was deposited in significantly higher amounts (p < 0.05) than n-6 PUFA, but both were consumed at similar amounts at 43.4% and 41.3%, respectively. The relatively low amount of C20:5n-3 and C22:6n-3 consumption may indicate these fatty acids were conserved, while the essential fatty acids C18:3n-3 and C18:3n-6 were consumed at high amounts. These findings may have implications for broodstock nutrition in order to formulate a well-balanced diet.     

Stereoselective Synthesis of (3R)‐3‐Alkyl‐4,1‐Benzoxazepine‐2,5‐Diones

Novel 3‐alkyl‐4,1‐benzoxazepine‐2,5‐diones were synthesized in good ee exploiting the chiral pool methodology, an economical way of asymmetric synthesis. Various anthranilic acids are coupled with different α‐haloacids to afford N‐acylated anthranilic acid intermediates which undergo cyclization to (3R)‐3‐alkyl‐4,1‐benzoxazepines‐2,5‐diones. Chirality 25:865–870, 2013. © 2013 Wiley Periodicals, Inc.     

Characterization and identification of compost bacteria based on 16S rRNA gene sequencing

The aim of this study was to isolate and characterize bacteria from the compost of fruit and vegetable waste (FVW) for plant growth-promoting (PGP) activities and investigate the pro-active influence of bacterial isolates on wheat growth. Fourteen bacterial strains (RHC-1 to RHC-14) were isolated and purified in tryptic soya agar (TSA). In addition to being biochemically characterized, these bacterial strains were also tested for their PGP traits, such as phosphate (P)-solubilization, nifH gene amplification, indole-3-acetic acid (IAA) quantification and the production of ammonia, oxidase and catalase. Based on 16S rRNA gene sequencing, these bacterial strains were identified as belonging to species of Bacillus, Lysinibacillus, Lysobacter, Staphylococcus, Enterobacter, Pseudomonas and Serratia. All bacterial strains solubilized tri-calcium phosphate and produced IAA. Two bacterial strains RHC-8 (Enterobacter sp.) and RHC-13 (Pseudomonas sp.) solubilized the maximum amount of tri-calcium phosphate, i.e. 486 and 464 μg/ml, respectively. P-solubilization was associated with a significant drop in the pH of the broth culture from an initial pH of 7 to pH 4.43. In addition to P-solubilization and IAA production, six bacterial strains also carried the nifH gene and were further evaluated for their effect on wheat (Triticum aestivum) growth under controlled conditions. All six bacterial strains enhanced wheat growth as compared to uninoculated control plants. Two of the bacterial strains, RHC-8 and RHC-13, identified as Enterobacter aerogenes and Pseudomonas brenneri, respectively, were assessed as potential PGP rhizobacteria due to exhibiting characteristics of four or more PGP traits and enhancing wheat growth though their specific mechanism of action.