Improving pharmacovigilance in Europe: TPMT genotyping and phenotyping in the UK and Spain.
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ABSTRACT:
SUBMITTER: Gurwitz D
PROVIDER: S-EPMC2986553 | biostudies-other | 2009 Aug
REPOSITORIES: biostudies-other
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Project description:The Innovative Medicines Initiative (IMI) WEB-RADR (Web-Recognising Adverse Drug Reactions) project looked at opportunities and challenges in using social media in pharmacovigilance as a rapidly evolving source of large, real-time data, which could provide new information on the actual use of medicines and potential safety issues. Two of the objectives were to develop principles for continuous monitoring of the safety of medicines without overburdening established pharmacovigilance systems and to propose a regulatory framework on the use of social media in pharmacovigilance. As a starting point, a review of existing legal requirements and regulatory guidance on social media use in pharmacovigilance was performed based on a survey conducted in 2014-2015. Furthermore, input from two large stakeholder workshops and evidence gathered from the research performed by WEB-RADR on the analysis of social media data were taken into consideration. Whilst analytical results of WEB-RADR indicated limited value of social media in detecting or confirming signals for a majority of the drugs studied, it is important to establish a regulatory framework for the use of social media in pharmacovigilance. Thus, the screening and reporting of suspected adverse reactions remains an important pillar in monitoring the safety and efficacy of medicines and the identification of new safety issues. Principles as to how social media can be used in pharmacovigilance are absolutely needed to provide clarity to patients, healthcare professionals, medicines regulators and the pharmaceutical industry.
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2019-01-28 | PXD010439 | Pride
Project description:BackgroundInformation on the genotypic diversity of Coxiella burnetii isolates from infected domestic ruminants in Spain is limited. The aim of this study was to identify the C. burnetii genotypes infecting livestock in Northern Spain and compare them to other European genotypes. A commercial real-time PCR targeting the IS1111a insertion element was used to detect the presence of C. burnetii DNA in domestic ruminants from Spain. Genotypes were determined by a 6-loci Multiple Locus Variable number tandem repeat analysis (MLVA) panel and Multispacer Sequence Typing (MST).ResultsA total of 45 samples from 4 goat herds (placentas, N = 4), 12 dairy cattle herds (vaginal mucus, individual milk, bulk tank milk, aerosols, N = 20) and 5 sheep flocks (placenta, vaginal swabs, faeces, air samples, dust, N = 21) were included in the study. Samples from goats and sheep were obtained from herds which had suffered abortions suspected to be caused by C. burnetii, whereas cattle samples were obtained from animals with reproductive problems compatible with C. burnetii infection, or consisted of bulk tank milk (BTM) samples from a Q fever surveillance programme. C. burnetii genotypes identified in ruminants from Spain were compared to those detected in other countries. Three MLVA genotypes were found in 4 goat farms, 7 MLVA genotypes were identified in 12 cattle herds and 4 MLVA genotypes were identified in 5 sheep flocks. Clustering of the MLVA genotypes using the minimum spanning tree method showed a high degree of genetic similarity between most MLVA genotypes. Overall 11 different MLVA genotypes were obtained corresponding to 4 different MST genotypes: MST genotype 13, identified in goat, sheep and cattle from Spain; MST genotype 18, only identified in goats; and, MST genotypes 8 and 20, identified in small ruminants and cattle, respectively. All these genotypes had been previously identified in animal and human clinical samples from several European countries, but some of the MLVA genotypes are described here for the first time.ConclusionsGenotyping revealed a substantial genetic diversity among domestic ruminants from Northern Spain.
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Project description:Phenotyping of 1,200 'healthy' adults from the UK has been performed through the investigation of diverse classes of hydrophilic and lipophilic metabolites present in serum by applying a series of chromatography-mass spectrometry platforms. These data were made robust to instrumental drift by numerical correction; this was prerequisite to allow detection of subtle metabolic differences. The variation in observed metabolite relative concentrations between the 1,200 subjects ranged from less than 5 % to more than 200 %. Variations in metabolites could be related to differences in gender, age, BMI, blood pressure, and smoking. Investigations suggest that a sample size of 600 subjects is both necessary and sufficient for robust analysis of these data. Overall, this is a large scale and non-targeted chromatographic MS-based metabolomics study, using samples from over 1,000 individuals, to provide a comprehensive measurement of their serum metabolomes. This work provides an important baseline or reference dataset for understanding the 'normal' relative concentrations and variation in the human serum metabolome. These may be related to our increasing knowledge of the human metabolic network map. Information on the Husermet study is available at http://www.husermet.org/. Importantly, all of the data are made freely available at MetaboLights (http://www.ebi.ac.uk/metabolights/).
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Project description:Here we report the discovery of a new late Lower Pleistocene site named Vallparadís (Barcelona, Spain) that produced a rich archeological and paleontological sequence dated from the upper boundary of the Jaramillo subchron to the early Middle Pleistocene. This deposit contained a main archeological layer with numerous artifacts and a rich macromammalian assemblage, some of which bore cut marks, that could indicate that hominins had access to carcasses. Paleomagnetic analysis, electron spin resonance-uranium series (ESR-US), and the biostratigraphic chronological position of the macro- and micromammal and lithic assemblages of this layer reinforce the proposal that hominins inhabited Europe during the Lower Pleistocene. The archeological sequence provides key information on the successful adaptation of European hominins that preceded the well-known fossil population from Atapuerca and succeeded the finds from Orce basin. Hence, this discovery enables us to close a major chronological gap in the early prehistory of Iberia. According to the information in this paper and the available data from these other sites, we propose that Mediterranean Western Europe was repeatedly and perhaps continuously occupied during the late Matuyama chron.
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Project description:To expedite immunotherapy development, better analysis of treatment efficacy at early in vitro stages is needed. Using a droplet-based microfluidic platform, we have established a method for multi-parameter quantifiable phenotypic and genomic observations of immunotherapies. Chimeric antigen receptor (CAR) NK cells provide treatment of interest in the current immunotherapy landscape and provide an optimal model for evaluating our novel methodology. For this approach, NK cells transduced with a CD19 CAR were compared to non-transduced NK cells in their ability to kill a lymphoma cell line. Using our novel single-cell droplet array platform, we quantified the increase in cytotoxicity and synaptic contact formation of CAR-NK cells over non-transduced NK cells. With our droplet sorter, we separated NK cells based on target cell killing for transcriptomic sequencing. Our data revealed expected improvement in cytotoxicity with the CD19 CAR but more importantly, provided unique insights into the factors involved in the cytotoxic mechanisms of CAR NK cells. This demonstrates a novel, improved system for immunotherapy screening.
2023-09-26 | GSE243787 | GEO
Project description:BackgroundTraditional methods for assessing prescriber knowledge can take several years to deliver results. This study was undertaken to obtain insights into the potential for using existing online communities to educate prescribers on therapy-related safety risks.ObjectiveThe aim of this study was to describe approaches to measuring prescribers' knowledge of safety risk (osteonecrosis of the jaw) outlined in the European Medicine Agency's summary of product characteristics for denosumab (XGEVA®).MethodsShort multiple-choice online instruments were administered as (1) a two-round cross-sectional survey fielded in January 2013-May 2015 (traditional, nine European countries, study duration: 3 years), (2) a survey targeting the online Medscape community (seven European countries, study duration: 3 weeks), and (3) a continuing medical education module with pre-/post-assessment in an online Medscape community (Medscape Education, USA). All respondents were oncologists; treated five or more patients with bone metastases from solid tumours in the previous 3 months; and prescribed denosumab within the previous 12 months. Medscape (a WebMD company, New York, NY, USA) is the leading online medical information resource, serving approximately 3 million physicians worldwide and 400,000 within Europe.ResultsIn the traditional 29-month study, 420 (n = 210 per round; 14% of screened physicians) individuals participated. Knowledge levels exceeded 75% correct on five questions (incidence of osteonecrosis of the jaw, concomitant risk factors and prevention of osteonecrosis of the jaw during denosumab treatment, importance of ensuring oral hygiene, and care for patients who have or develop osteonecrosis of the jaw) with less awareness of optimal osteonecrosis of the jaw treatment. The Medscape survey (n = 207; 32.1% of 645 eligible) provided similar results in a 3-week post-survey launch. The Medscape Education study (n = 264) documented knowledge acquisition.ConclusionsAssessments that target physicians through online platforms where they seek information about drug-related safety risks may result in increased efficiencies, informing regulators about prescribers' knowledge of safe use within weeks rather than years. Online communities or professional societies may provide venues in which to implement knowledge-acquisition surveys tied to training/education modules that address safety topics.
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Project description:Background:In the early stages of plant breeding programs high-quality phenotypes are still a constraint to improve genetic gain. New field-based high-throughput phenotyping (HTP) platforms have the capacity to rapidly assess thousands of plots in a field with high spatial and temporal resolution, with the potential to measure secondary traits correlated to yield throughout the growing season. These secondary traits may be key to select more time and most efficiently soybean lines with high yield potential. Soybean average canopy coverage (ACC), measured by unmanned aerial systems (UAS), is highly heritable, with a high genetic correlation with yield. The objective of this study was to compare the direct selection for yield with indirect selection using ACC and using ACC as a covariate in the yield prediction model (Yield|ACC) in early stages of soybean breeding. In 2015 and 2016 we grew progeny rows (PR) and collected yield and days to maturity (R8) in a typical way and canopy coverage using a UAS carrying an RGB camera. The best soybean lines were then selected with three parameters, Yield, ACC and Yield|ACC, and advanced to preliminary yield trials (PYT). Results:We found that for the PYT in 2016, after adjusting yield for R8, there was no significant difference among the mean performances of the lines selected based on ACC and Yield. In the PYT in 2017 we found that the highest yield mean was from the lines directly selected for yield, but it may be due to environmental constraints in the canopy growth. Our results indicated that PR selection using Yield|ACC selected the most top-ranking lines in advanced yield trials. Conclusions:Our findings emphasize the value of aerial HTP platforms for early stages of plant breeding. Though ACC selection did not result in the best performance lines in the second year of selections, our results indicate that ACC has a role in the effective selection of high-yielding soybean lines.
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