FISHBURNE's METHOD AND THE CLASSICAL METHOD OF PHARMACOECONOMIC ANALYSIS IN THE EVALUATION OF ANTIBIOTIC TREATMENT OF ACUTE AND RECURRENT BRONCHITIS IN CHILDREN

Objective: This study was performed in order to estimate clinical effectiveness of antibiotic therapy in acute and recurrent obstructive bronchitis. For estimation the following was used: the Fishbern method of antibiotics distribution according to clinical effectiveness levels with the help of weighted coefficients and classical cost–efficiency†pharmacoeconomic analysis of the given antibiotic therapy. Then, for the first time ever, the obtained results of both methods were combined.Methods: Materials were presented by the data on antibiotic therapy, given for patients who were hospitalized to the in-patient medical facilities due to acute or recurrent obstructive bronchitis. Medical records of 2 259 patients were included in the study. The patients were 0 to 18 y old. In order to determine the weighed coefficients of each used antibiotic with subsequent distribution according to the levels of clinical effectiveness the Fishbern method was applied. Three levels of clinical effectiveness were used in this study, i.e. high, medium and low. The cost–efficiency†pharmacoeconomic analysis was applied to combine costs and efficiency of the compared therapy courses in acute and recurrent obstructive bronchitis.Results: Finally we found out that the highest probability of positive effect of cephalosporins group agents was associated with the use of Cefotaximum. (Biosynthesis). From the pharmacoeconomic point of view the most effective in treating acute and recurrent obstructive bronchitis in children in the in-patient facilities was Ceftriaxonum (Synthesis). Out of protected penicillins group, we used Amoxicillin/clavulanic acid–original drug Augmentin (Smithkline Beecham Pharmaceuticals) and generic drug Amoxiclav (Lek d. d). Augmentin effectiveness was 0.591, and Amoxiclav effectiveness–0.530. Cost of Augmentin treatment course was 106.26 rub. (1.68 US$), cost of Amoxiclav treatment course–103.50 rub.(1.63 US$). Augmentin use turned out to be the most reasonable. Augmentin treatment course was characterized by lower ICER coefficient versus Amoxiclav. We found out that from the pharmacoeconomic point of view Azitromicin (Vertex Ltd.) treatment turned out to be the most reasonable of the whole macrolides antibiotics for treatment of acute and recurrent obstructive bronchitis. However, according to the Fishbern clinical effectiveness classification this antibiotic belonged to the group with medium effectiveness level. The group with high effectiveness level included Sumamed, Azitral, Hemomicin, Clacid, Zitrocin and Clabax. Clacid and Clabax were excluded during the pharmacoeconomic analysis. The highest value of ICER coefficient was obtained for Sumamed and made up 39,367.50 rub. (621.53 US$). The highest level of clinical effectiveness was characteristic for Sumamed as well. Besides Sumamed was an original drug of azitromicin. According to the obtained data Azitral and Hemomicin had the lowest values of ICER coefficient (1151.67 rub. (18.18 US$) and 1812.22 rub. (28.61 US$) respectively). Therefore based on the clinical economic analysis these medical agents turned out to be the most suitable.Conclusion: The results of the pharmacoeconomic analysis showed that the most effective drugs in treatment of acute and recurrent obstructive bronchitis in children in in-patient facilities appeared to be the following: out of cephalosporins-Ceftriaxonum (Synthesis), out of protected penicillins-Augmentin (Smithkline Beecham Pharmaceuticals), out of macrolides-Azitromicin (Vertex Ltd.). According to the Fishbern classification, these drugs belonged to the group with medium level of effectiveness.Â

ROLE OF "ATYPICAL" MICROORGANISMS ON THE FORMATION OF BRONCHIAL ASTHMA IN CHILDREN WITH ACUTE AND RECURRENT OBSTRUCTIVE BRONCHITIS

Objective: This study was undertaken to determine the link between the presence of atypical†infections in patients with acute obstructive andrecurrent obstructive bronchitis (AOB/ROB) and bronchial asthma (BA) development based on the concept of risk.Methods: The materials for the study were the data records of patients hospitalized with AOB or ROB and whose analysis was performed to identifyantibodies to atypical†microflora (796 patients). The study period was 4 years from 2008 to 2011. In the analyzed period, immunosorbent assay forthe detection of antibodies to atypical†microflora (Chlamydophila pneumoniae, Mycoplasma pneumoniae, Mycoplasma hominis) was performed. Theconcept of risk identification was based on the determination of the absolute risk, attributable risk (AtR), relative risk, population attributable risk, aswell as on the definition of the standard errors for each type of risk and the confidence interval.Results and Conclusion: Methodical aspects of determining the relationship between the presence of atypical†infections in patients with AOBor ROB and BA development were based on the concept of risk. The analysis showed a direct link between the increase of cases of BA formationagainst the backdrop of atypical†infections. Therefore, the performed analysis of atypical pathogens influences on BA occurrence in patients withAOB/ROB which indicates direct dependence increase of BA incidence on atypical infection. In experimental group, Frequency of event is 14.84% inexperimental group. Frequency of event is 1.67% in control group. The risk factor increases probability of event by 13.17%, the risk factor increasesprobability of event by 13.17%. Presence of atypical infection leads to increase of BA incidence by 8.9 times. Number needed to harm (NNH) is 7.59,i.e., in the presence of atypical infection in patients with AOB/ROB, each eighth exposed person develops BA in addition to background level of BAincidence.Keywords: Acute obstructive bronchitis, Recurrent obstructive bronchitis, Bronchial asthma, The concept of risk, Risk factor, The absolute risk,Relative risk, Attributable risk, Population attributable risk, Number needed to harm

WATER-SOLUBLE POLYMERIC IONIC 5-FLUOROURACIL COMPLEX BASED ON METHACRYLIC ACID COPOLYMERS

Objective: The objective of this work was to obtain a water-soluble 5-fluorouracil (5-FU) polymeric complex on the basis of a methacrylic acid (MAA) copolymer to be used as an injectable chemotherapeutic agent. Methods: A polymeric carrier was synthesized using tert-butyl methacrylate (TBMA) as a monomer, thioglycolic acid, and azobisisobutyronitrile as a radical polymerization initiator. The polymer was converted by acid hydrolysis into a water-soluble copolymer of TBMA and MAA of 20: 80 mass%, respectively. The copolymer of TBMA and MAA was modified with 5-FU. Their formation was proved using IR and UV spectroscopy. The particle size of the 5-FU polymeric complex was estimated by turbidimetry, which is based on measuring the intensity of light transmitted through a disperse system. The release of 5-FU from the obtained ionic complexes by dialysis in vitro was evaluated. Results: Polymeric carriers were obtained with different amounts of 5-FU (5, 15, 25, 50 mol%). A high peak at λ = 266 nm was observed in the UV spectrum of the polymeric carrier (characteristic of 5-FU). The particle size was estimated at 13 nm for the complex with 5 mol% 5-FU and 26.8 n for the complex with 50 mol% 5-FU. The 5-FU release was estimated in two parallel experiments at 37 °C. One utilized a phosphate-citrate buffer with pH 5.0 to model the intracellular space and the other, a phosphate buffer with pH 7.4 to model the intravascular space. Two systems, with 5 and 15 mol% 5-FU, were chosen for testing. In both phosphate buffer and phosphate-citrate buffer, 5-FU was released from the polymeric complex with 5 mol% 5-FU approximately 1.3 times faster than from the complex containing 5 mol% 5-fluorouracil. The kinetics of 5-FU release from the polymeric complex (5 mol% 5-fluorouracil) showed that the 5-FU release was 77.9% in phosphate-citrate buffer and 59.6% in phosphate buffer over 52 h of dialysis. When the 5-FU release kinetics was studied with the polymeric complex containing 15 mol% 5-FU, the 5-FU release was 100.0% in phosphate-citrate buffer and 75.1% in phosphate buffer over 57 h of dialysis. Conclusion: Water-soluble nanoscale complexes of 5-FU with TBMA–MAA copolymers extend application of 5-FU, while its general toxicity might be lower. The complexes are sufficiently stable at pH 7.4 and readily release 5-FU at pH 5.0

Tree canopy affects soil macrofauna spatial patterns on broad- and meso- scale levels in an Eastern European poplar-willow forest in the floodplain of the River Dnipro

This paper tested the hypothesis that the placement of trees in the floodplain ecosystem leads to multiscale spatial structuring and plays an important role in formation of the spatial patterns of the soil macrofauna. The research polygon was laid in an Eastern European poplar-willow forest in the floodplain of the River Dnipro. The litter macrofauna was manually collected from the soil samples. The distances of the sampling locations from the nearest individual of each tree species were applied to obtain a measure of the overstorey spatial structure. The pure effect of tree structured space on the soil animal community was presented by the broad-scale and meso-scale components. The soil animal community demonstrated patterns varying in tree structured space. The tree induced spatial heterogeneity was revealed to effect on the vertical stratification of the soil animal community. The complex nature of the soil animal community variability depending on the distance from trees was depended on the interaction of tree species in their effects on soil animals. The importance of the spatial structures that interact with soil, plants and tree factors in shaping soil macrofauna communities was shown

Tree canopy affects soil macrofauna spatial patterns on broad- and meso- scale levels in an Eastern European poplar-willow forest in the floodplain of the River Dnipro

This paper tested the hypothesis that the placement of trees in the floodplain ecosystem leads to multiscale spatial structuring and plays an important role in formation of the spatial patterns of the soil macrofauna. The research polygon was laid in an Eastern European poplar-willow forest in the floodplain of the River Dnipro. The litter macrofauna was manually collected from the soil samples. The distances of the sampling locations from the nearest individual of each tree species were applied to obtain a measure of the overstorey spatial structure. The pure effect of tree structured space on the soil animal community was presented by the broad-scale and meso-scale components. The soil animal community demonstrated patterns varying in tree structured space. The tree induced spatial heterogeneity was revealed to effect on the vertical stratification of the soil animal community. The complex nature of the soil animal community variability depending on the distance from trees was depended on the interaction of tree species in their effects on soil animals. The importance of the spatial structures that interact with soil, plants and tree factors in shaping soil macrofauna communities was shown

A global view of the OCA2-HERC2 region and pigmentation

Mutations in the gene OCA2 are responsible for oculocutaneous albinism type 2, but polymorphisms in and around OCA2 have also been associated with normal pigment variation. In Europeans, three haplotypes in the region have been shown to be associated with eye pigmentation and a missense SNP (rs1800407) has been associated with green/hazel eyes (Branicki et al. in Ann Hum Genet 73:160–170, 2009). In addition, a missense mutation (rs1800414) is a candidate for light skin pigmentation in East Asia (Yuasa et al. in Biochem Genet 45:535–542, 2007; Anno et al. in Int J Biol Sci 4, 2008). We have genotyped 3,432 individuals from 72 populations for 21 SNPs in the OCA2-HERC2 region including those previously associated with eye or skin pigmentation. We report that the blue-eye associated alleles at all three haplotypes were found at high frequencies in Europe; however, one is restricted to Europe and surrounding regions, while the other two are found at moderate to high frequencies throughout the world. We also observed that the derived allele of rs1800414 is essentially limited to East Asia where it is found at high frequencies. Long-range haplotype tests provide evidence of selection for the blue-eye allele at the three haplotyped systems but not for the green/hazel eye SNP allele. We also saw evidence of selection at the derived allele of rs1800414 in East Asia. Our data suggest that the haplotype restricted to Europe is the strongest marker for blue eyes globally and add further inferential evidence that the derived allele of rs1800414 is an East Asian skin pigmentation allele

European Atlas of Natural Radiation

Natural ionizing radiation is considered as the largest contributor to the collective effective dose received by the world population. The human population is continuously exposed to ionizing radiation from several natural sources that can be classified into two broad categories: high-energy cosmic rays incident on the Earth’s atmosphere and releasing secondary radiation (cosmic contribution); and radioactive nuclides generated during the formation of the Earth and still present in the Earth’s crust (terrestrial contribution). Terrestrial radioactivity is mostly produced by the uranium and thorium radioactive families together with potassium. In most circumstances, radon, a noble gas produced in the radioactive decay of uranium, is the most important contributor to the total dose. This Atlas aims to present the current state of knowledge of natural radioactivity, by giving general background information, and describing its various sources. This reference material is complemented by a collection of maps of Europe displaying the levels of natural radioactivity caused by different sources. It is a compilation of contributions and reviews received from more than 80 experts in their field: they come from universities, research centres, national and European authorities and international organizations. This Atlas provides reference material and makes harmonized datasets available to the scientific community and national competent authorities. In parallel, this Atlas may serve as a tool for the public to: • familiarize itself with natural radioactivity; • be informed about the levels of natural radioactivity caused by different sources; • have a more balanced view of the annual dose received by the world population, to which natural radioactivity is the largest contributor; • and make direct comparisons between doses from natural sources of ionizing radiation and those from man-made (artificial) ones, hence to better understand the latter.JRC.G.10-Knowledge for Nuclear Security and Safet

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio