60 research outputs found

    Identification and Description of the Uncertainty, Variability, Bias and Influence in Quantitative Structure-Activity Relationships (QSARs) for Toxicity Prediction

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    Improving regulatory confidence in, and acceptance of, a prediction of toxicity from a quantitative structure-activity relationship (QSAR) requires assessment of its uncertainty and determination of whether the uncertainty is acceptable. Thus, it is crucial to identify potential uncertainties fundamental to QSAR predictions. Based on expert review, sources of uncertainties, variabilities and biases, as well as areas of influence in QSARs for toxicity prediction were established. These were grouped into three thematic areas: uncertainties, variabilities, potential biases and influences associated with 1) the creation of the QSAR, 2) the description of the QSAR, and 3) the application of the QSAR, also showing barriers for their use. Each thematic area was divided into a total of 13 main areas of concern with 49 assessment criteria covering all aspects of QSAR development, documentation and use. Two case studies were undertaken on different types of QSARs that demonstrated the applicability of the assessment criteria to identify potential weaknesses in the use of a QSAR for a specific purpose such that they may be addressed and mitigation strategies can be proposed, as well as enabling an informed decision on the adequacy of the model in the considered context

    Thresholds of Toxicological Concern for Cosmetics-Related Substances: New Database, Thresholds, and Enrichment of Chemical Space

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    A new dataset of cosmetics-related chemicals for the Threshold of Toxicological Concern (TTC) approach has been compiled, comprising 552 chemicals with 219, 40, and 293 chemicals in Cramer Classes I, II, and III, respectively. Data were integrated and curated to create a database of No-/Lowest-Observed-Adverse-Effect Level (NOAEL/LOAEL) values, from which the final COSMOS TTC dataset was developed. Criteria for study inclusion and NOAEL decisions were defined, and rigorous quality control was performed for study details and assignment of Cramer classes. From the final COSMOS TTC dataset, human exposure thresholds of 42 and 7.9 μg/kg-bw/day were derived for Cramer Classes I and III, respectively. The size of Cramer Class II was insufficient for derivation of a TTC value. The COSMOS TTC dataset was then federated with the dataset of Munro and colleagues, previously published in 1996, after updating the latter using the quality control processes for this project. This federated dataset expands the chemical space and provides more robust thresholds. The 966 substances in the federated database comprise 245, 49 and 672 chemicals in Cramer Classes I, II and III, respectively. The corresponding TTC values of 46, 6.2 and 2.3 μg/kg-bw/day are broadly similar to those of the original Munro dataset

    Efficacy and safety of a multifactor intervention to improve therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): protocol for the ICEPOC study

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    <p>Abstract</p> <p>Background</p> <p>Low therapeutic adherence to medication is very common. Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment. The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is extremely poor according to most studies. The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence. Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients.</p> <p>Methods/Design</p> <p>A randomized controlled clinical trial with 140 COPD diagnosed patients selected by a non-probabilistic method of sampling. Subjects will be randomly allocated into two groups, using the block randomization technique. Every patient in each group will be visited four times during the year of the study. Intervention: Motivational aspects related to adherence (beliefs and behaviour): group and individual interviews; cognitive aspects: information about illness; skills: inhaled technique training. Reinforcement of the cognitive-emotional aspects and inhaled technique training will be carried out in all visits of the intervention group.</p> <p>Discussion</p> <p>Adherence to a prescribed treatment involves a behavioural change. Cognitive, emotional and motivational aspects influence this change and so we consider the best intervention procedure to improve adherence would be a cognitive and emotional strategy which could be applied in daily clinical practice. Our hypothesis is that the application of a multifactor intervention (COPD information, dose reminders and reinforcing audiovisual material, motivational aspects and inhalation technique training) to COPD patients taking inhaled treatment will give a 25% increase in the number of patients showing therapeutic adherence in this group compared to the control group.</p> <p>We will evaluate the effectiveness of this multifactor intervention on patient adherence to inhaled drugs considering that it will be right and feasible to the clinical practice context.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISCTN18841601">ISCTN18841601</a></p

    A realist analysis of hospital patient safety in Wales:Applied learning for alternative contexts from a multisite case study

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    Background: Hospital patient safety is a major social problem. In the UK, policy responses focus on the introduction of improvement programmes that seek to implement evidence-based clinical practices using the Model for Improvement, Plan-Do-Study-Act cycle. Empirical evidence that the outcomes of such programmes vary across hospitals demonstrates that the context of their implementation matters. However, the relationships between features of context and the implementation of safety programmes are both undertheorised and poorly understood in empirical terms. Objectives: This study is designed to address gaps in conceptual, methodological and empirical knowledge about the influence of context on the local implementation of patient safety programmes. Design: We used concepts from critical realism and institutional analysis to conduct a qualitative comparative-intensive case study involving 21 hospitals across all seven Welsh health boards. We focused on the local implementation of three focal interventions from the 1000 Lives+ patient safety programme: Improving Leadership for Quality Improvement, Reducing Surgical Complications and Reducing Health-care Associated Infection. Our main sources of data were 160 semistructured interviews, observation and 1700 health policy and organisational documents. These data were analysed using the realist approaches of abstraction, abduction and retroduction. Setting: Welsh Government and NHS Wales. Participants: Interviews were conducted with 160 participants including government policy leads, health managers and professionals, partner agencies with strategic oversight of patient safety, advocacy groups and academics with expertise in patient safety. Main outcome measures: Identification of the contextual factors pertinent to the local implementation of the 1000 Lives+ patient safety programme in Welsh NHS hospitals. Results: An innovative conceptual framework harnessing realist social theory and institutional theory was produced to address challenges identified within previous applications of realist inquiry in patient safety research. This involved the development and use of an explanatory intervention–context–mechanism–agency–outcome (I-CMAO) configuration to illustrate the processes behind implementation of a change programme. Our findings, illustrated by multiple nested I-CMAO configurations, show how local implementation of patient safety interventions are impacted and modified by particular aspects of context: specifically, isomorphism, by which an intervention becomes adapted to the environment in which it is implemented; institutional logics, the beliefs and values underpinning the intervention and its source, and their perceived legitimacy among different groups of health-care professionals; and the relational structure and power dynamics of the functional group, that is, those tasked with implementing the initiative. This dynamic interplay shapes and guides actions leading to the normalisation or the rejection of the patient safety programme. Conclusions: Heightened awareness of the influence of context on the local implementation of patient safety programmes is required to inform the design of such interventions and to ensure their effective implementation and operationalisation in the day-to-day practice of health-care teams. Future work is required to elaborate our conceptual model and findings in similar settings where different interventions are introduced, and in different settings where similar innovations are implemented. Funding: The National Institute for Health Research Health Services and Delivery Research programme
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