IntroductionRapid increase in the number of elderly patients in the world who need dialysis treatment. High age with dementio depression and anxiety negatively affects the outcome of hemodyalisis ...patients on (HD).ObjectivesThe goal is that patients get the ability to choose by themselves will they start HD treatment or not. The old population is often exposed doctors, family or guardian’s descisions that are against their wishes, either due to a lack of communication or lack of knowledge of working methods and procedures. Procedures can leave mental and physical consequences (suffering), no matter they were all done professionally.MethodsWe analyzed old (70-75 years) and very old patients (over 80 years). Cross-sectional analysis of survival of patients at the Hemodialysis (HD) Center with standard methods.ResultsFor patients who started hemodialysis at the age of 70 or more, the average survival was: 20.27±18.62 months, those who died 15.54±17.35, and living ones 30.29±17.85. 35% of the patients survived up to one year, two years 18%, and 3 or more 8%.Most of old people that started dialysis treatment afterwards complained and concluded that it wasn’t necessary mostly because of the lack of communication, or simply it wasn’t their own decision.Based on these facts, and knowing that these procedures can leave mental and physical consequences subjective assessment about starting dialysis treatment should respect, in the first place, patient’s decision.The plan for medical procedure involves great ethical, legal and psychological engagment. It often occurs in people who, for some reason, are not in contact and do not adequately test reality.ConclusionsWe are of the opinion that it is, therefore, important that every person, while in mental, physical and social well-being, makes a decision about his medical treatment and communicates it to his family, but it is also very difficult because it touches on his own mortality and helplessness.Disclosure of InterestNone Declared
•A strategy to evaluate chemical category membership is presented.•Templates to assess similarity and characterise uncertainty are developed.•A strategy to apply new toxicological data to strengthen ...read-across predictions.•A workflow for reporting a read-across prediction is described.•Read-across prediction to aid in regulatory decisions.
Category formation, grouping and read across methods are broadly applicable in toxicological assessments and may be used to fill data gaps for chemical safety assessment and regulatory decisions. In order to facilitate a transparent and systematic approach to aid regulatory acceptance, a strategy to evaluate chemical category membership, to support the use of read-across predictions that may be used to fill data gaps for regulatory decisions is proposed. There are two major aspects of any read-across exercise, namely assessing similarity and uncertainty. While there can be an over-arching rationale for grouping organic substances based on molecular structure and chemical properties, these similarities alone are generally not sufficient to justify a read-across prediction. Further scientific justification is normally required to justify the chemical grouping, typically including considerations of bioavailability, metabolism and biological/mechanistic plausibility. Sources of uncertainty include a variety of elements which are typically divided into two main issues: the uncertainty associated firstly with the similarity justification and secondly the completeness of the read-across argument. This article focuses on chronic toxicity, whilst acknowledging the approaches are applicable to all endpoints. Templates, developed from work to prepare for the application of new toxicological data to read-across assessment, are presented. These templates act as proposals to assist in assessing similarity in the context of chemistry, toxicokinetics and toxicodynamics as well as to guide the systematic characterisation of uncertainty both in the context of the similarity rationale, the read across data and overall approach and conclusion. Lastly, a workflow for reporting a read-across prediction is suggested.
•PBK models have helped to facilitate quantitative in vitro to in vivo extrapolation.•PBK modelling has the potential to play a significant role in reducing animal testing.•It is critical to assess ...the validity of PBK models built using non-animal data.•A framework is needed for communicating characteristics and results of PBK modelling.
The fields of toxicology and chemical risk assessment seek to reduce, and eventually replace, the use of animals for the prediction of toxicity in humans. In this context, physiologically based kinetic (PBK) modelling based on in vitro and in silico kinetic data has the potential to a play significant role in reducing animal testing, by providing a methodology capable of incorporating in vitro human data to facilitate the development of in vitro to in vivo extrapolation of hazard information. In the present article, we discuss the challenges in: 1) applying PBK modelling to support regulatory decision making under the toxicology and risk-assessment paradigm shift towards animal replacement; 2) constructing PBK models without in vivo animal kinetic data, while relying solely on in vitro or in silico methods for model parameterization; and 3) assessing the validity and credibility of PBK models built largely using non-animal data. The strengths, uncertainties, and limitations of PBK models developed using in vitro or in silico data are discussed in an effort to establish a higher degree of confidence in the application of such models in a regulatory context. The article summarises the outcome of an expert workshop hosted by the European Commission Joint Research Centre (EC-JRC) – European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM), on “Physiologically-Based Kinetic modelling in risk assessment – reaching a whole new level in regulatory decision-making” held in Ispra, Italy, in November 2016, along with results from an international survey conducted in 2017 and recently reported activities occurring within the PBK modelling field. The discussions presented herein highlight the potential applications of next generation (NG)-PBK modelling, based on new data streams.
In the last 20 years, alternative approaches to the identification of skin sensitisation hazards have been at the forefront of the 3Rs and have helped refine the validation and acceptance processes. ...However, experience with the local lymph node assay showed that, post-validation, challenges still occurred, particularly when a wider diversity of chemical substances was addressed, a situation which will arise with validated in vitro alternatives. In the present work, a range of substances potentially challenging to assess in current nonanimal OECD test guidelines were evaluated in several of the emerging in vitro alternatives. Twelve such substances (of which just over half were known skin sensitisers) were assessed in 4 assays, all based on reconstructed human epidermis (RHE) models. For hazard identification, the overall predictive accuracy ranged around 70% for three assays, although for one (SensCeeTox), it fell below 50% when human data was used as the benchmark. In most cases, sensitivity was high, such that sensitisation was overpredicted. As the substances were challenging to assess in other nonanimal methods, the results indicate that the 3D RHE models may be a useful tool for assessing skin sensitisation potentials without needing to revert to animal use.
•Toxicological assays are rarely applicable to all types of test substances.•Recently validated skin sensitisation in vitro methods generally require dissolution in aqueous media.•Application of test chemicals to reconstructed human skin surface is an alternative.•A range of such models have been assessed with 12 challenging chemicals.•Results demonstrate that these models may help, but are not a perfect solution.
Skin metabolism is important to consider when assessing local toxicity and/or penetration of chemicals and their metabolites. If human skin supply is limited, pig skin can be used as an alternative. ...To identify any species differences, we have investigated the metabolism of 10 chemicals in a pig and human skin explant model. Phase I metabolic pathways in skin from both species included those known to occur via cytochrome P450s, esterases, alcohol dehydrogenases and aldehyde dehydrogenases. Common Phase II pathways were glucuronidation and sulfation but other conjugation pathways were also identified. Chemicals not metabolized by pig skin (caffeine, IQ and 4‐chloroaniline) were also not metabolized by human skin. Six chemicals metabolized by pig skin were metabolized to a similar extent (percentage parent remaining) by human skin. Human skin metabolites were also detected in pig skin incubations, except for one unidentified minor vanillin metabolite. Three cinnamyl alcohol metabolites were unique to pig skin but represented minor metabolites. There were notable species differences in the relative amounts of common metabolites. The difference in the abundance of the sulfate conjugates of resorcinol and 4‐amino‐3‐nitrophenol was in accordance with the known lack of aryl sulfotransferase activity in pigs. In conclusion, while qualitative comparisons of metabolic profiles were consistent between pig and human skin, there were some quantitative differences in the percentage of metabolites formed. This preliminary assessment suggests that pig skin is metabolically competent and could be a useful tool for evaluating potential first‐pass metabolism before testing in human‐derived tissues.
We have investigated the metabolism of 10 chemicals in viable pig and human skin. Phase I and II metabolic pathways were present in skin from both species. Chemicals not metabolized by pig skin were also not metabolized by human skin. Six chemicals metabolized by pig skin were also metabolized to a similar extent by human skin. Pig and human skin produced common metabolites, although some species differences were observed and as their relative amounts differed.
The Cosmetics Europe Skin Bioavailability and Metabolism Task Force aims to improve the measurement and prediction of the bioavailability of topically-exposed compounds for risk assessment. Key ...parameters of the experimental design of the skin penetration studies were compared. Penetration studies with frozen human and pig skin were conducted in two laboratories, according to the SCCS and OECD 428 guidelines. The disposition in skin was measured 24h after finite topical doses of caffeine, resorcinol and 7-ethoxycoumarin. The bioavailability distribution in skin layers of cold and radiolabelled chemicals were comparable. Furthermore, the distribution of each chemical was comparable in human and pig skin. The protocol was reproducible across the two laboratories. There were small differences in the amount of chemical detected in the skin layers, which were attributed to differences in washing procedures and anatomical sites of the skin used. In conclusion, these studies support the use of pig skin as an alternative source of skin should the availability of human skin become a limiting factor. If radiolabelled chemicals are not available, cold chemicals can be used, provided that the influence of chemical stability, reactivity or metabolism on the experimental design and the relevance of the data obtained is considered.
Introduction
Peritoneal dialysis (PD) is an equal method of treating patients with end stage renal disease ( ESRD). The patients are left to themselves in the new situation. The psychiatrist ...recognizes their needs and through group therapy enables them to heal quality intrapsychic conflicts.
Objectives
The study analized data on the intensity of depression, anxiety of an individual patient respectively, but also of his family member (caregiver) too. The control questionnaires are foreseen for both groups one year after group therapy participation. The assumption is that symptoms of depression and anxiety will be less expressed with group support by the psychiatrist.
Methods
Two questionnaires were used: Hamilton’s rating scale for depression and Hamilton’s anxiety rating scale and identical questionnaires for member of the family caring for the patients. 13 patients who accepted group therapy were examined in our institution. They were of different gender and age, mean age 53±13.46 mini-max 25-72 years.
Results
Average months of dialysis duration 29.15±21.84 min-max 6-84 Dialysis was performed without an assistant but with some help n 13( 100%) from the patient. They describe ailments from anxiety (30.77%) and depression ( 38.46% ) which they did not have premorbidly, and feel rejected on the emotional sphere, although not on the part of organic medicine.
Conclusions
Emphasis is placed on the emotional state and needs of the patient with severe physical ailments, in other words, demanding treatment methods, as well as the importance of emotional support from family members without whom these patients would have a poorer quality of life.
Disclosure
No significant relationships.
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