A mathematical framework to quantify the masking effect associated with the confidence intervals of measures of disproportionality

Background: The lower bound of the 95% confidence interval of measures of disproportionality (Lower95CI) is widely used in signal detection. Masking is a statistical issue by which true signals of disproportionate reporting are hidden by the presence of other medicines. The primary objective of our study is to develop and validate a mathematical framework for assessing the masking effect of Lower95CI. Methods: We have developed our new algorithm based on the masking ratio (MR) developed for the measures of disproportionality. A MR for the Lower95CI (MRCI) is proposed. A simulation study to validate this algorithm was also conducted. Results: We have established the existence of a very close mathematical relation between MR and MRCI. For a given drug–event pair, the same product will be responsible for the highest masking effect with the measure of disproportionality and its Lower95CI. The extent of masking is likely to be very similar across the two methods. An important proportion of identical drug–event associations affected by the presence of an important masking effect is revealed by the unmasking exercise, whether the proportional reporting ratio (PRR) or its confidence interval are used. Conclusion: The detection of the masking effect of Lower95CI can be automated. The real benefits of this unmasking in terms of new true-positive signals (rate of true-positive/false-positive) or time gained by the revealing of signals using this method have not been fully assessed. These benefits should be demonstrated in the context of prospective studies. </jats:sec

Association between gastric acid suppressants and Clostridium difficile colitis and community-acquired pneumonia: analysis using pharmacovigilance tools

SummaryObjectiveRecent epidemiological studies identifying an association between some classes of gastric acid suppressants and Clostridium difficile colitis and community-acquired pneumonia prompted our analysis. Our objective was to retrospectively apply data mining algorithms (DMAs) to the Food and Drug Administration (FDA) drug safety database to see if they might have directed/redirected attention to the reported association of gastric acid suppressive drugs with C. difficile colitis and community-acquired pneumonia, prior to the published epidemiological findings that supported the association.DesignTwo statistical DMAs, proportional reporting ratios (PRRs) and multi-item gamma Poisson shrinker (MGPS), were applied to a spontaneous reporting system (SRS) database to identify signals of disproportionate reporting (SDRs).ResultsSDRs related to community-acquired pneumonia were observed for two proton pump inhibitors (lansoprazole and omeprazole), two H2 antagonists (famotidine and roxatidine), and one antacid (magnesium silicate hydroxide). For C. difficile colitis, an SDR was generated for one proton pump inhibitor (lansoprazole).ConclusionsAlthough our analysis suggests that there may be an association between the SDRs using SRS data and the epidemiological findings, these results may not have alerted public health professionals in advance of published studies to an association between proton pump inhibitors/gastric acid suppressants and C. difficile colitis or community-acquired pneumonia. However, the analysis reveals the potential utility of DMAs to direct attention to more subtle indirect drug adverse effects in SRS databases that as yet are often identified from epidemiological investigations

Study to gather evidence on the working conditions of platform workers VT/2018/032 Final Report 13 December 2019

Platform work is a type of work using an online platform to intermediate between platform workers, who provide services, and paying clients. Platform work seems to be growing in size and importance. This study explores platform work in the EU28, Norway and Iceland, with a focus on the challenges it presents to working conditions and social protection, and how countries have responded through top-down (e.g. legislation and case law) and bottom-up actions (e.g. collective agreements, actions by platform workers or platforms). This national mapping is accompanied by a comparative assessment of selected EU legal instruments, mostly in the social area. Each instrument is assessed for personal and material scope to determine how it might impact such challenges. Four broad legal domains with relevance to platform work challenges are examined in stand-alone reflection papers. Together, the national mapping and legal analysis support a gap analysis, which aims to indicate where further action on platform work would be useful, and what form such action might take

Assessing the Impact of European Governments' Austerity Plans on the Rights of People with Disabilities

Since the onset of the economic crisis in 2008, concerns have been raised by all interested parties on the negative impacts for people with disabilities. This study, which was commissioned by the European Consortium of Foundations on Human Rights and Disability, examines evidence at both European and national level of the effect of the economic crisis, in terms of austerity measures, on the rights and status of people with disabilities. A core team of European researchers, complemented by national experts in six EU Member States, conducted an independent survey of documentary sources and carried out interviews with funders, providers and organisations of people with disabilities. The countries included in the study were Greece, Hungary, Ireland, Portugal, Spain and the UK.The findings are linked back to the UN Convention on the Rights of Persons with Disabilities (UNCRPD) and the objectives of the EU Disability Strategy

Rapid Acquisition of Gigapascal-High-Pressure Resistance by Escherichia coli

Pressure and temperature are important environmental variables that influence living systems. However, while they vary over a considerable range on Earth and other planets, it has hardly been addressed how straightforwardly and to what extent cellular life can acquire resistance to extremes of these parameters within a defined genomic context and a limited number of generations. Nevertheless, this is a very pertinent question with respect to the penetration of life in allegedly inhospitable environments. In this study, directed evolution was used to reveal the potential of the nonsporulating and mesophilic model bacterium Escherichia coli to develop the ability to survive exposure to high temperature or pressure. While heat resistance could only marginally be increased, our data show that piezoresistance could readily and reproducibly be extended into the GPa range, thereby greatly exceeding the currently recognized maximum for growth or survival

Pre-conditioning the epigenetic response to high vapor pressure deficit increases the drought tolerance of Arabidopsis thaliana

Epigenetic modification of the genome via cytosine methylation is a dynamic process that responds to changes in the growing environment. This modification can also be heritable. The combination of both properties means that there is the potential for the life experiences of the parental generation to modify the methylation profiles of their offspring and so potentially to ‘pre-condition’ them to better accommodate abiotic conditions encountered by their parents. We recently identified high vapor pressure deficit (vpd)-induced DNA methylation at two gene loci in the stomatal development pathway and an associated reduction in leaf stomatal frequency.1 Here, we test whether this epigenetic modification pre-conditioned parents and their offspring to the more severe water stress of periodic drought. We found that three generations of high vpd-grown plants were better able to withstand periodic drought stress over two generations. This resistance was not directly associated with de novo methylation of the target stomata genes, but was associated with the cmt3 mutant’s inability to maintain asymmetric sequence context methylation. If our finding applies widely, it could have significant implications for evolutionary biology and breeding for stressful environments

Genome Sequence of Stenotrophomonas maltophilia PML168, Which Displays Baeyer-Villiger Monooxygenase Activity

Stenotrophomonas maltophilia PML168 was isolated from Wembury Beach on the English Coast from a rock pool following growth and selection on agar plates. Here we present the permanent draft genome sequence, which has allowed prediction of function for several genes encoding enzymes relevant to industrial biotechnology, including a novel flavoprotein monooxygenase

Assessing the Association of Pioglitazone Use and Bladder Cancer Through Drug Adverse Event Reporting

OBJECTIVE\u2014To analyze the association between pioglitazone use and bladder cancer through a spontaneous adverse event reporting system for medications. RESEARCH DESIGN AND METHODS\u2014Case/noncase bladder cancer reports associated with antidiabetic drug use were retrieved from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) between 2004 and 2009 and analyzed by the reporting odds ratio (ROR). RESULTS\u2014Ninety-three reports of bladder cancer were retrieved, corresponding to 138 drug reaction pairs (pioglitazone, 31; insulin, 29; metformin, 25; glimepiride, 13; exenatide, 8; others, 22). RORwas indicative of a definite risk for pioglitazone (4.30 [95%CI 2.82\u20136.52]), and a much weaker risk for gliclazide and acarbose, with very few cases being treated with these two drugs (6 and 4, respectively). CONCLUSIONS\u2014In agreement with preclinical and clinical studies, AERS analysis is consistent with an association between pioglitazone and bladder cancer. This issue needs constant epidemiologic surveillance and urgent definition by more specific studies