The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We ...investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.
In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol.
Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 48·7% women; median age 51·0 years IQR 40·7–59·7). 199 415 individuals were included in the derivation cohort (91 786 48·4% women) and 199 431 (92 269 49·1% women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0–1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6–2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0–1·3 to 2·3, 2·0–2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced.
Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician–patient communication about primary prevention strategies.
EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.
Informing Decisions in a Changing Climate National Research Council; Division of Behavioral and Social Sciences and Education; Committee on the Human Dimensions of Global Change ...
06/2009
eBook
Open access
Everyone-government agencies, private organizations, and individuals-is facing a changing climate: an environment in which it is no longer prudent to follow routines based on past climatic averages. ...State and local agencies in particular, as well as the federal government, need to consider what they will have to do differently if the 100-year flood arrives every decade or so, if the protected areas for threatened species are no longer habitable, or if a region can expect more frequent and more severe wildfires, hurricanes, droughts, water shortages, or other extreme environmental events. Both conceptually and practically, people and organizations will have to adjust what may be life-long assumptions to meet the potential consequences of climate change. How and where should bridges be built? What zoning rules may need to be changed? How can targets for reduced carbon emissions be met? These and myriad other questions will need to be answered in the coming years and decades.
Informing Decisions in a Changing Climate examines the growing need for climate-related decision support-that is, organized efforts to produce, disseminate, and facilitate the use of data and information in order to improve the quality and efficacy of climate-related decisions. Drawing on evidence from past efforts to organize science for improved decision making, it develops guidance for government agencies and other institutions that will provide or use information for coping with climate change. This volume provides critical analysis of interest to agencies at every level, as well as private organizations that will have to cope with the world's changing climate.
The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human ...health risk assessment and ethics of this system, demanding a change of paradigm. At the same time, the scientific toolbox used for risk assessment is continuously enriched by the development of “New Approach Methodologies” (NAMs). While this term does not define the age or the state of readiness of the innovation, it covers a wide range of methods, including quantitative structure–activity relationship (QSAR) predictions, high-throughput screening (HTS) bioassays, omics applications, cell cultures, organoids, microphysiological systems (MPS), machine learning models and artificial intelligence (AI). In addition to promising faster and more efficient toxicity testing, NAMs have the potential to fundamentally transform today’s regulatory work by allowing more human-relevant decision-making in terms of both hazard and exposure assessment. Yet, several obstacles hamper a broader application of NAMs in current regulatory risk assessment. Constraints in addressing repeated-dose toxicity, with particular reference to the chronic toxicity, and hesitance from relevant stakeholders, are major challenges for the implementation of NAMs in a broader context. Moreover, issues regarding predictivity, reproducibility and quantification need to be addressed and regulatory and legislative frameworks need to be adapted to NAMs. The conceptual perspective presented here has its focus on hazard assessment and is grounded on the main findings and conclusions from a symposium and workshop held in Berlin in November 2021. It intends to provide further insights into how NAMs can be gradually integrated into chemical risk assessment aimed at protection of human health, until eventually the current paradigm is replaced by an animal-free “Next Generation Risk Assessment” (NGRA).
Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these ...risks.
We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens.
The authors participated in a workshop held 4-8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development "hot spots," exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options.
Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental "hot spot" compartments; and c) modifying traditional dose-response approaches to address doses of ARB for various health outcomes and pathways.
We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers.
The triple disaster that struck Japan in March 2011 forced people living there to confront new risks in their lives. Despite the Japanese government's reassurance that radiation exposure would be ...small and unlikely to affect the health of the general population, many questioned the government's commitment to protecting their health. The disaster prompted them to become vigilant about limiting their risk exposure, and food emerged as a key area where citizens could determine their own levels of acceptable risk.
Food Safety after Fukushima examines the process by which notions about what is safe to eat were formulated after the nuclear meltdown. Its central argument is that as citizens informed themselves about potential risks, they also became savvier in their assessment of the government's handling of the crisis. The author terms this "Scientific Citizenship," and he shows that the acquisition of scientific knowledge on the part of citizens resulted in a transformed relationship between individuals and the state. Groups of citizens turned to existing and newly formed organizations where food was sourced from areas far away from the nuclear accident or screened to stricter standards than those required by the state. These organizations enabled citizens to exchange information about the disaster, meet food producers, and work to establish networks of trust where food they considered safe could circulate.
Based on extensive fieldwork and interviews with citizens groups, mothers' associations, farmers, government officials, and retailers, Food Safety after Fukushima reflects on how social relations were affected by the accident. The author vividly depicts an environment where trust between food producers and consumers had been shaken, where people felt uneasy about their food choices and the consequences they might have for their children, and where farmers were forced to deal with the consequences of pollution that was not of their making. Most poignantly, the book conveys the heavy burden now attached to the name "Fukushima" in the popular imagination and explores efforts to resurrect it.
The ecosystem services approach has gained broad interest in regulatory and policy circles for use in ecological risk assessment. Whilst identifying several challenges, scientific experts from ...European regulatory authorities, the chemical industry and academia considered the approach applicable to all chemical sectors and potentially contributing to greater ecological relevance for setting and assessing environmental protection goals compared to current European regulatory frameworks for chemicals. These challenges were addressed in workshops to develop a common understanding across stakeholders on how the ecosystem services concept might be used in chemical risk assessment and what would need to be done to implement it. This paper describes the consensus outcome of those discussions. Knowledge gaps and research needs were identified and prioritised, exploring the use of novel approaches from ecology, ecotoxicology and ecological modelling. Where applicable, distinction is made between prospective and retrospective ecological risk assessment. For prospective risk assessment the development of environmental scenarios accounting for chemical exposure and ecological conditions was designated as a top priority. For retrospective risk assessment the top priority research need was development of reference conditions for key ecosystem services and guidance for their derivation. Both prospective and retrospective risk assessment would benefit from guidance on the taxa and measurement endpoints relevant to specific ecosystem services and from improved understanding of the relationships between measurement endpoints from standard toxicity tests and the ecosystem services of interest (i.e. assessment endpoints). The development of mechanistic models, which could serve as ecological production functions, was identified as a priority. A conceptual framework for future chemical risk assessment based on an ecosystem services approach is presented.
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•The ecosystem services (ES) approach has potential to enhance ecological and societal relevance in ERA.•Stakeholders in EU regulation, industry, academia and NGOs agreed on priority research needs.•A framework for future chemical risk assessment based on an ES approach is presented.•Further development may benefit from recent progress in other disciplines.
Aquatic environments are identified as an ideal setting for acquisition and dissemination of antibiotic resistance, and human exposure to antibiotic resistant bacteria (ARB) and antibiotic resistance ...genes (ARGs) in aquatic environments may pose an additional health risk. Quantitative microbial risk assessment (QMRA) has been suggested as a suitable method to evaluate and quantify this health risk. However, information about the exposure to ARB and ARGs in aquatic environments is lacking for many scenarios and dose-response models regarding the ARB infections are not developed yet. This review summarizes the current knowledge regarding the ARB and ARGs in aquatic environments and highlights the challenging questions remaining to be answered to better forecast the health risks caused by ARB and ARGs in water environments. The questions include what are the missing information needed to quantify the human health risks caused by exposing to ARB and ARGs in aquatic environments? what are the suitable markers to evaluate the ARB/ARGs contamination in aquatic environments? how frequently do the ARG selection and propagation occur in aquatic environments? and are there any unknown hot spots? Studies on the above topics will contribute to better management of antibiotic resistance dissemination in water environments and its risks on human health.
Abbreviations
3GC
3
rd
generation cephalosporins
ARB
Antibiotic resistant bacteria
ARG
Antibiotic resistance gene
CFU
Colony forming unit
DBP
Disinfection by-products
eDNA
Extracellular DNA
EPS
Extracellular polymeric substances
HGT
Horizontal gene transfer
ISCR
Insertion sequence common region
MAR
Multiple antibiotic resistant
MIC
Minimum inhibitory concentration
MGE
Mobile genetic elements
MSW
Municipal solid waste
QMRA
Quantitative microbial risk assessment
VBNC
Viable but non-culturable
WWTP
Wastewater treatment plant
The net reclassification improvement (NRI) is an increasingly popular measure for evaluating improvements in risk predictions. This article details a review of 67 publications in high-impact general ...clinical journals that considered the NRI. Incomplete reporting of NRI methods, incorrect calculation, and common misinterpretations were found. To aid improved applications of the NRI, the article elaborates on several aspects of the computation and interpretation in various settings. Limitations and controversies are discussed, including the effect of miscalibration of prediction models, the use of the continuous NRI and “clinical NRI,” and the relation with decision analytic measures. A systematic approach toward presenting NRI analysis is proposed: Detail and motivate the methods used for computation of the NRI, use clinically meaningful risk cutoffs for the category-based NRI, report both NRI components, address issues of calibration, and do not interpret the overall NRI as a percentage of the study population reclassified. Promising NRI findings need to be followed with decision analytic or formal cost-effectiveness evaluations.
The future of risk assessment Zio, E.
Reliability engineering & system safety,
September 2018, 2018-09-00, 20180901, 2018-09, Volume:
177
Journal Article
Peer reviewed
Open access
•A view on the future of risk assessment is provided.•Research directions are presented on the use of simulation for accident scenario identification and exploration.•The use of data for condition ...monitoring-based, dynamic risk assessment is discussed.•The extension of risk assessment into the framework of resilience and business continuity is presented.•The directions for and integrated safety and security assessment of CPSs are discussed.
Risk assessment must evolve for addressing the existing and future challenges, and considering the new systems and innovations that have already arrived in our lives and that are coming ahead. In this paper, I swing on the rapid changes and innovations that the World that we live in is experiencing, and analyze them with respect to the challenges that these pose to the field of risk assessment. Digitalization brings opportunities but with it comes also the complexity of cyber-phyiscal systems. Climate change and extreme natural events are increasingly threatening our infrastructures; terrorist and malevolent threats are posing severe concerns for the security of our systems and lives. These sources of hazard are extremely uncertain and, thus, difficult to describe and model quantitatively.
Some research and development directions that are emerging are presented and discussed, also considering the ever increasing computational capabilities and data availability. These include the use of simulation for accident scenario identification and exploration, the extension of risk assessment into the framework of resilience and business continuity, the reliance on data for dynamic and condition monitoring-based risk assessment, the safety and security assessment of cyber-physical systems.
The paper is not a research work and not exactly a review or a state of the art work, but rather it offers a lookout on risk assessment, open to consideration and discussion, as it cannot pretend to give an absolute point of view nor to be complete in the issues addressed (and the related literature referenced to).
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