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tuberculosis lineages. This analysis demonstrated extensive homoplasy of repeat numbers, but did not detect any evidence of natural selection of repeat numbers, at least since the ancestral branching of the three modern lineages of M. tuberculosis. In addition, we observed good sensitivity but poor specificity and positive predictive values of MIRU-24 to detect clusters of recent transmission, as defined by whole-genome single nucleotide polymorphism analysis. These findings provide mechanistic insight, and support a transition away from VNTR-based typing toward sequence-based typing schemes for both research and public health purposes.Introduction Antimicrobial resistance (AMR) is a current global health threat and a challenge to the treatment of infectious diseases. The WHO advocates a strategy of antibiotic stewardship programs (ASP) in optimizing antimicrobial use in hospitals. This study aimed at assessing the existence of AMR surveillance and ASP implementation in health facilities in Tanzania in the year following the launch of the National Action Plan (NAP). Methodology From December 2017 through July 2018, a descriptive cross-sectional study was conducted using a structured questionnaire administered online. A total of 199 health facilities in Tanzania mainland whose contacts was obtained from the Ministry of Health Community Development Gender Elderly and Children (MoHCDGEC) were reached by phone and thereafter, a survey was sent via text or e-mail to focal persons in the corresponding facilities. Results Only 39 (32.5%) responses from contacted facilities were received and analyzed. Thirty (76.9%) of the facilities were governmeny found the existence of AMR surveillance activities and ASP implementation in Tanzania, albeit at a low level. The implementation was inconsistent across the surveyed facilities. These data have identified areas of improvement in addressing AMR in Tanzania through the NAP.Volatile organic compounds (VOCs) are present in several working activities. This work is aimed at comparing oxidative stress and DNA damage biomarkers to specific VOCs in the occupational exposure of painters. Dose-response relationships between biomarkers of oxidative stress and of dose were studied. Unmetabolized VOCs and their urinary metabolites were analyzed. Urinary Methylhyppuric acids (MHIPPs, xylenes metabolite), Phenylglyoxylic and Mandelic acid (PGA, MA ethylbenzene metabolites), S-Benzylmercapturic acid (SBMA, toluene metabolite), and S-Phenylmercapturic acid (SPMA, benzene metabolite) were quantified at the end of work-shift. Oxidative stress was determined by urinary excretion of 8-oxodGuo, 8-oxoGua and 8-oxoGuo and direct/oxidative DNA damage in blood by Fpg-Comet assay. Multivariate linear regression models were used to assess statistical significance of the association between dose and effect biomarkers. The regressions were studied with and without the effect of hOGG1 and XRCC1 gene polymorphisms. Statistically significant associations were found between MHIPPs and both 8-oxoGuo and oxidative DNA damage effect biomarkers measured with the Comet assay. Oxidative DNA damage results significantly associated with airborne xylenes and toluene, whilst 8-oxodGuo was significantly related to urinary xylenes and toluene. Direct DNA damage was significantly associated to SBMA. XRCC1 wild-type gene polymorphism was significantly associated with lower oxidative and total DNA damage with respect to heterozygous and mutant genotypes. The interpretation of the results requires some caution, as the different VOCs are all simultaneously present in the mixture and correlated among them.The aim of the current study was to compare pricing methodologies at the manufacturer, wholesale, and retail levels, and to estimate the price differences of AT1-receptor blockers (sartans), Angiotensin-converting enzyme (ACE)-inhibitors, and their fixed-dose combinations (FDCs) in four countries using similar methodologies Slovakia, Greece, Bulgaria, and Romania (SK, GR, BG, and RO, respectively). The methodologies for manufacturer, wholesale, and retail price establishment have been compared using nationally implemented rules. Overlapping trademarks were established retrospectively on the manufacturer and retail levels in November 2017. The average price per tablet, percentage of price deviation, and statistically significant differences were calculated. The selected countries apply external reference pricing at the manufacturer level. ML-SI3 solubility dmso A wide variation in the number of referent countries was observed (from 12 to 27). Despite the use of a regressive scale for price calculation, large variations between margins and value-added tax (VAT) are established, thus leading to different final medicine prices. This study found that medicine prices were lower in RO than in other selected countries. It was caused by the fact that 15 products had the lowest manufacturer price and 14 products had the lowest retail price in RO. Results of Kruskal-Wallis test showed that there were no significant differences between prices per tablet on the manufacturer and retail levels. In the group of fixed-dose combinations, ramipril/hydrochlorothiazide, and irbesartan/hydrochlorothiazide showed more than 100% deviation. The prices of cardiovascular medicines differed within the observed countries. The differences in pricing methodologies (e.g., margins, VAT) at the national level did not significantly affect retail prices, as a low manufacturer price usually leads to a low retail price.Objectives To analyse the market shares of biosimilars in Slovakia and to calculate the potential cost-savings from the use of biosimilars in Slovakia based on two different data sources. Methods National reimbursement lists from the Czech Republic, Hungary, Poland and Slovakia were used for analyzing the availability of biosimilars with public funding. In addition, the reimbursement dossiers of biosimilars, the justifications of reimbursement decisions by the Slovak Ministry of Health, and final reimbursement decrees, which are published on the webpage of the Slovak Ministry of Health, were utilized for this study. Reimbursement decisions regarding biosimilars by the Slovak Ministry of Health from 2006 to August 2019 were considered and the detailed utilization of biosimilars in 2018 was analyzed based on data from the State Institute for Drug Control. The study was validated based on data from the Slovak National Health Information Center. Results Fifty four biosimilars were approved by the European Medicines Agency (EMA) in August 2019.

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