Zoekresultaten

Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins

From the publisher: "Background: The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). Main body: The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell-cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. Conclusion: The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs." Authors: Jolanda H. M. van BilsenEmail author, Edyta Sienkiewicz-Szłapka, Daniel Lozano-Ojalvo, Linette E. M. Willemsen, Celia M. Antunes, Elena Molina, Joost J. Smit, Barbara Wróblewska, Harry J. Wichers, Edward F. Knol, Gregory S. Ladics, Raymond H. H. Pieters, Sandra Denery-Papini, Yvonne M. Vissers, Simona L. Bavaro, Colette Larré, Kitty C. M. Verhoeckx and Erwin L. Roggen

Regional variations in childbirth interventions and their correlations with adverse outcomes, birthplace and care provider

Background Variations in childbirth interventions may indicate inappropriate use. Most variation studies are limited by the lack of adjustments for maternal characteristics and do not investigate variations in adverse outcomes. This study aims to explore regional variations in the Netherlands and their correlations with referral rates, birthplace, interventions, and adverse outcomes, adjusted for maternal characteristics. Methods In this nationwide retrospective cohort study, using a national data register, intervention rates were analysed between twelve regions among single childbirths after 37 weeks’ gestation in 2010–2013 (n = 614,730). These were adjusted for maternal characteristics using multivariable logistic regression. Primary outcomes were intrapartum referral, birthplace, and interventions used in midwife- and obstetrician-led care. Correlations both between primary outcomes and between adverse outcomes were calculated with Spearman’s rank correlations. Findings Intrapartum referral rates varied between 55–68% (nulliparous) and 20–32% (multiparous women), with a negative correlation with receiving midwife-led care at the onset of labour in two-thirds of the regions. Regions with higher referral rates had higher rates of severe postpartum haemorrhages. Rates of home birth varied between 6–16% (nulliparous) and 16–31% (multiparous), and was negatively correlated with episiotomy and postpartum oxytocin rates. Among midwife-led births, episiotomy rates varied between 14–42% (nulliparous) and 3–13% (multiparous) and in obstetrician-led births from 46–67% and 14–28% respectively. Rates of postpartum oxytocin varied between 59–88% (nulliparous) and 50–85% (multiparous) and artificial rupture of membranes between 43–52% and 54–61% respectively. A north-south gradient was visible with regard to birthplace, episiotomy, and oxytocin. Conclusions Our study suggests that attitudes towards interventions vary, independent of maternal characteristics. Care providers and policy makers need to be aware of reducing unwarranted variation in birthplace, episiotomy and the postpartum use of oxytocin. Further research is needed to identify explanations and explore ways to reduce unwarranted intervention rates.

Adverse effects of anxiety on attentional control differ as a function of experience

Pediatric Sedation in Dutch Dental Clinics: The Influence of Guideline Modifications on Adverse Events

Background: Dental fear and uncooperative behavior can hinder dental treatment quality. Pediatric Procedural Sedation and Analgesia (PPSA) is used to facilitate treatment when the coping capacity is exceeded. Out-of-hospital PPSA has been associated with more adverse outcomes compared to when it is used in hospital-based settings. The updated Dutch PPSA guidelines have increased costs and raised concerns about the accessibility of specialized high-quality dental care for children in the Netherlands. This study aimed to investigate the impact of the updated 2017 guidelines on the occurrence rate of adverse events during PPSA in twelve Dutch dental clinics. Methods: The data of 25,872 children who were treated at twelve dental clinics between 1997 and 2019 were analyzed. A logistic two-level mixed-effects model was used to estimate the updated guidelines’ impacts on adverse events. Results: The OR of the occurrence rate of an adverse event adjusted for age, weight, and duration of treatment was 0.75 (95% CI 0.64–0.89) after the implementation of the updated guidelines. This outcome was significant with p = 0.001, indicating a protective effect. Conclusions: Our findings demonstrate that there was a significant reduction in adverse events after the implementation of the updated guideline and highlight the importance of adhering to evidence-based practices in out-of-hospital dental clinics.

Natural language processing in toxicology: Delineating adverse outcome pathways and guiding the application of new approach methodologies

Adverse Outcome Pathways (AOPs) are conceptual frameworks that tie an initial perturbation (molecular initiat- ing event) to a phenotypic toxicological manifestation (adverse outcome), through a series of steps (key events). They provide therefore a standardized way to map and organize toxicological mechanistic information. As such, AOPs inform on key events underlying toxicity, thus supporting the development of New Approach Methodologies (NAMs), which aim to reduce the use of animal testing for toxicology purposes. However, the establishment of a novel AOP relies on the gathering of multiple streams of evidence and infor- mation, from available literature to knowledge databases. Often, this information is in the form of free text, also called unstructured text, which is not immediately digestible by a computer. This information is thus both tedious and increasingly time-consuming to process manually with the growing volume of data available. The advance- ment of machine learning provides alternative solutions to this challenge. To extract and organize information from relevant sources, it seems valuable to employ deep learning Natural Language Processing techniques. We review here some of the recent progress in the NLP field, and show how these techniques have already demonstrated value in the biomedical and toxicology areas. We also propose an approach to efficiently and reliably extract and combine relevant toxicological information from text. This data can be used to map underlying mechanisms that lead to toxicological effects and start building quantitative models, in particular AOPs, ultimately allowing animal-free human-based hazard and risk assessment.

Tailoring of exercise and dietary interventions to adverse effects and existing comorbidities in patients with ovarian cancer receiving chemotherapy

Purpose: This study aims to capture the complex clinical reasoning process during tailoring of exercise and dietary interventions to adverse effects and comorbidities of patients with ovarian cancer receiving chemotherapy. Methods: Clinical vignettes were presented to expert physical therapists (n = 4) and dietitians (n = 3). Using the think aloud method, these experts were asked to verbalize their clinical reasoning on how they would tailor the intervention to adverse effects of ovarian cancer and its treatment and comorbidities. Clinical reasoning steps were categorized in questions raised to obtain additional information; anticipated answers; and actions to be taken. Questions and actions were labeled according to the evidence-based practice model. Results: Questions to obtain additional information were frequently related to the patients’ capacities, safety or the etiology of health issues. Various hypothetical answers were proposed which led to different actions. Suggested actions by the experts included extensive monitoring of symptoms and parameters, specific adaptations to the exercise protocol and dietary-related patient education. Conclusions: Our study obtained insight into the complex process of clinical reasoning, in which a variety of patient-related variables are used to tailor interventions. This insight can be useful for description and fidelity assessment of interventions and training of healthcare professionals.