Consumption of antibiotics in the community, European Union/European Economic Area, 1997-2017: data collection, management and analysis

This article introduces a series of articles on antibiotic consumption in the community between 1997 and 2017, which provide an update of previous articles covering the periods 1997-2003 and 1997-2009.In this article, differences in participating countries, the ATC/DDD classification system, and data collection, validation and analysis between the current and previous series are described.In the previous series, 33 European countries provided valid data for further analysis, while the current series focused on 30 countries belonging to the EU or the European Economic Area (EEA). For both series, data were collected in accordance with the WHO ATC classification system. While the previous series reported data in accordance with the ATC/DDD index 2011, the current series employed the ATC/DDD index 2019. Both series focused on consumption of antibacterials for systemic use (ATC J01) and collected data expressed in DDD per 1000 inhabitants per day and packages per 1000 inhabitants per day. When studying consumption expressed in packages per 1000 inhabitants per day, countries reporting total care data, i.e. community and hospital sector combined, were included in the previous series but excluded in the current series. While the previous series used non-linear mixed models to evaluate time trends in antibiotic consumption, the current series allowed for inclusion of change-points with a data-driven location. In addition, both series assessed the composition and quality of antibiotic consumption in the EU/EEA.The updated analyses of two decades of ESAC-Net data provide the most comprehensive and detailed description of antibiotic consumption in the community in Europe

Analysing the trend over time of antibiotic consumption in the community

This tutorial describes and illustrates statistical methods to detect time trends possibly including abrupt changes (referred to as change-points) in the consumption of antibiotics in the community.For the period 1997-2017, data on consumption of antibacterials for systemic use (ATC group J01) in the community, aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day. Trends over time and presence of common change-points were studied through a set of non-linear mixed models.After a thorough description of the set of models used to assess the time trend and presence of common change-points herein, the methodology was applied to the consumption of antibacterials for systemic use (ATC J01) in 25 EU/European Economic Area (EEA) countries. The best fit was obtained for a model including two change-points: one in the first quarter of 2004 and one in the last quarter of 2008.Allowing for the inclusion of common change-points improved model fit. Individual countries investigating changes in their antibiotic consumption pattern can use this tutorial to analyse their country data

Change-points in antibiotic consumption in the community, European Union/European Economic Area, 1997-2017

Surveillance of antibiotic consumption in the community is of utmost importance to inform and evaluate control strategies. Data on two decades of antibiotic consumption in the community were collected from 30 EU/European Economic Area (EEA) countries. This article reviews temporal trends and the presence of abrupt changes in subgroups of relevance in antimicrobial stewardship.For the period 1997-2017, data on yearly antibiotic consumption in the community, aggregated at the level of the active substance, were collected using the WHO ATC classification and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day. We applied a range of non-linear mixed models to assess the presence of changes in the consumption of antibacterials for systemic use (ATC group J01) and eight antibiotic subgroups.For the majority of the studied groups, a country-specific change-point model provided the best fit. Depending on the antibiotic group/subgroup and on the country, change-points were spread out between 2000 and 2013.Due to the heterogeneity in antibiotic consumption in the community across EU/EEA countries, a country-specific change-point model provided the better fit. Given the limitations of this model, our recommendation for the included countries is to carefully interpret the country-specific results presented in this article and to use the tutorial included in this series to conduct their own change-point analysis when evaluating the impact of changes in regulations, public awareness campaigns, and other national interventions to improve antibiotic consumption in the community

Guidance on the Selection of Appropriate Indicators for Quantification of Antimicrobial Usage in Humans and Animals

An increasing variety of indicators of antimicrobial usage has become available in human and veterinary medicine, with no consensus on the most appropriate indicators to be used. The objective of this review is therefore to provide guidance on the selection of indicators, intended for those aiming to quantify antimicrobial usage based on sales, deliveries or reimbursement data. Depending on the study objective, different requirements apply to antimicrobial usage quantification in terms of resolution, comprehensiveness, stability over time, ability to assess exposure and comparability. If the aim is to monitor antimicrobial usage trends, it is crucial to use a robust quantification system that allows stability over time in terms of required data and provided output; to compare usage between different species or countries, comparability must be ensured between the different populations. If data are used for benchmarking, the system comprehensiveness is particularly crucial, while data collected to study the association between usage and resistance should express the exposure level and duration as a measurement of the exerted selection pressure. Antimicrobial usage is generally described as the number of technical units consumed normalized by the population at risk of being treated in a defined period. The technical units vary from number of packages to number of individuals treated daily by adding different levels of complexity such as daily dose or weight at treatment. These technical units are then related to a description of the population at risk, based either on biomass or number of individuals. Conventions and assumptions are needed for all of these calculation steps. However, there is a clear lack of standardization, resulting in poor transparency and comparability. By combining study requirements with available approaches to quantify antimicrobial usage, we provide suggestions on the most appropriate indicators and data sources to be used for a given study objective

GATE : a simulation toolkit for PET and SPECT

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols, and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at the address http://www-lphe.epfl.ch/GATE/

Clear-PEM: A PET imaging system dedicated to breast cancer diagnostics

The Clear-PEM scanner for positron emission mammography under development is described. The detector is based on pixelized LYSO crystals optically coupled to avalanche photodiodes and readout by a fast low-noise electronic system. A dedicated digital trigger (TGR) and data acquisition (DAQ) system is used for on-line selection of coincidence events with high efficiency, large bandwidth and small dead-time. A specialized gantry allows to perform exams of the breast and of the axilla. In this paper we present results of the measurement of detector modules that integrate the system under construction as well as the imaging performance estimated from Monte Carlo simulated data.http://www.sciencedirect.com/science/article/B6TJM-4M942B5-D/1/e8aea93baa1aeae3538ea200a5a5466

Number of addictive substances used related to increased risk of unnatural death: A combined medico-legal and case-record study

<p>Abstract</p> <p>Background</p> <p>Substance use disorders have repeatedly been found to lead to premature death, i.e. drug-related death by disease, fatal intoxications, or trauma (accidents, suicide, undetermined suicide, and homicide). The present study examined the relationship between multi-drug substance use and natural and unnatural death.</p> <p>Methods</p> <p>All consecutive, autopsied patients who had been in contact with the Addiction Centre in Malmö University Hospital from 1993 to 1997 inclusive were investigated. Drug abuse was investigated blindly in the case records and related to the cause of death in 387 subjects.</p> <p>Results</p> <p>Every substance apart from alcohol used previously in life added to the risk of unnatural death in a linear way. There were independent increased risks of fatal heroin overdoses or undetermined suicide. Death by suicide and violent death were unrelated to additional abuse.</p> <p>Conclusion</p> <p>The number of drugs used was related to an increased risk of unnatural death by undetermined suicide (mainly fatal intoxications) and heroin overdose.</p

Glacial Refugia in Pathogens: European Genetic Structure of Anther Smut Pathogens on Silene latifolia and Silene dioica

Climate warming is predicted to increase the frequency of invasions by pathogens and to cause the large-scale redistribution of native host species, with dramatic consequences on the health of domesticated and wild populations of plants and animals. The study of historic range shifts in response to climate change, such as during interglacial cycles, can help in the prediction of the routes and dynamics of infectious diseases during the impending ecosystem changes. Here we studied the population structure in Europe of two Microbotryum species causing anther smut disease on the plants Silene latifolia and Silene dioica. Clustering analyses revealed the existence of genetically distinct groups for the pathogen on S. latifolia, providing a clear-cut example of European phylogeography reflecting recolonization from southern refugia after glaciation. The pathogen genetic structure was congruent with the genetic structure of its host species S. latifolia, suggesting dependence of the migration pathway of the anther smut fungus on its host. The fungus, however, appeared to have persisted in more numerous and smaller refugia than its host and to have experienced fewer events of large-scale dispersal. The anther smut pathogen on S. dioica also showed a strong phylogeographic structure that might be related to more northern glacial refugia. Differences in host ecology probably played a role in these differences in the pathogen population structure. Very high selfing rates were inferred in both fungal species, explaining the low levels of admixture between the genetic clusters. The systems studied here indicate that migration patterns caused by climate change can be expected to include pathogen invasions that follow the redistribution of their host species at continental scales, but also that the recolonization by pathogens is not simply a mirror of their hosts, even for obligate biotrophs, and that the ecology of hosts and pathogen mating systems likely affects recolonization patterns

Potential cellular and biochemical mechanisms of exercise and physical activity on the ageing process

Exercise in young adults has been consistently shown to improve various aspects of physiological and psychological health but we are now realising the potential benefits of exercise with advancing age. Specifically, exercise improves cardiovascular, musculoskeletal, and metabolic health through reductions in oxidative stress, chronic low-grade inflammation and modulating cellular processes within a variety of tissues. In this this chapter we will discuss the effects of acute and chronic exercise on these processes and conditions in an ageing population, and how physical activity affects our vasculature, skeletal muscle function, our immune system, and cardiometabolic risk in older adults