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Onset and transition of and recovery from adverse development

AIM: Early intervention programs for first-episode psychosis have led to the awareness that the period before onset of a first episode is important in light of early intervention. This has induced a focus on the so-called 'at risk mental state' (ARMS). Individuals with ARMS are at increased risk for later psychotic disorder, but also for other psychiatric disorders as well as poor psychosocial functioning. Thus, adequate detection and treatment of ARMS is essential.METHODS: Since 2018, screening for and treatment of ARMS is recommended standard care in the Netherlands. Implementation is still ongoing. We initiated a naturalistic long-term cohort study of ARMS individuals, the onset and transition of and recovery from adverse development (OnTheROAD) study, with the aim to monitor course and outcome of symptoms and psychosocial functioning over time, as well as patterns of comorbidity and associations with factors of risk and resilience. To this end, participants complete a broad battery of instruments at baseline and yearly follow-up assessments up to 3 years. Outcome is defined in terms of symptom severity level, functioning and quality of life. In particular, we aim to investigate the impact of negative symptoms as part of the ARMS concept. Results from this study can aid in refining the existing ARMS criteria, understanding the developmental course of ARMS and investigating the hypothesized pluripotentiality in outcome of ARMS. New knowledge may inform the further development of specialized early interventions.RESULTS AND CONCLUSIONS: In this article, we describe the rationale, outline and set-up of OnTheROAD.

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Adverse events following cervical manual physical therapy techniques

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Prevalence of and relationship between adverse childhood experiences and family context risk factors among children with intellectual disabilities and borderline intellectual functioning

Background: Adverse Childhood Experiences (ACEs) are an overlooked risk factor for behavioural, mental and physical health disparities in children with intellectual disabilities (ID) and borderline intellectual functioning (BIF). Aims: To gain insight into the presence of the 10 original Wave II ACEs and family context risk variables in a convenience sample of children with ID and BIF in Dutch residential care. Methods and procedures: 134 case-files of children with ID (n = 82) and BIF (n = 52) were analysed quantitatively. Outcomes and results: 81.7 % of the children with ID experienced at least 1 ACE, as did 92.3 % of the children with BIF. The average number of ACEs in children with ID was 2.02 (range 0???? 8) and in children with BIF 2.88 (range 0???? 7). About 20 % of the children with moderate and mild ID experienced 4 ACEs or more. Many of their families faced multiple and complex problems (ID: 69.5 %; BIF 86.5 %). Multiple regression analysis indicated an association between family context risk variables and the number of ACEs in children. Conclusions and implications: The prevalence of ACEs in children with ID and BIF appears to be considerably high. ACEs awareness in clinical practice is vital to help mitigate negative outcomes.

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Prevalence of and relationship between adverse childhood experiences and family context risk factors among children with intellectual disabilities and borderline intellectual functioning

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Optimization of an adverse outcome pathway network on chemical-induced cholestasis using an artificial intelligence-assisted data collection and confidence level quantification approach

Background: Adverse outcome pathway (AOP) networks are versatile tools in toxicology and risk assessment that capture and visualize mechanisms driving toxicity originating from various data sources. They share a common structure consisting of a set of molecular initiating events and key events, connected by key event relationships, leading to the actual adverse outcome. AOP networks are to be considered living documents that should be frequently updated by feeding in new data. Such iterative optimization exercises are typically done manually, which not only is a time-consuming effort, but also bears the risk of overlooking critical data. The present study introduces a novel approach for AOP network optimization of a previously published AOP network on chemical-induced cholestasis using artificial intelligence to facilitate automated data collection followed by subsequent quantitative confidence assessment of molecular initiating events, key events, and key event relationships. Methods: Artificial intelligence-assisted data collection was performed by means of the free web platform Sysrev. Confidence levels of the tailored Bradford-Hill criteria were quantified for the purpose of weight-of-evidence assessment of the optimized AOP network. Scores were calculated for biological plausibility, empirical evidence, and essentiality, and were integrated into a total key event relationship confidence value. The optimized AOP network was visualized using Cytoscape with the node size representing the incidence of the key event and the edge size indicating the total confidence in the key event relationship. Results: This resulted in the identification of 38 and 135 unique key events and key event relationships, respectively. Transporter changes was the key event with the highest incidence, and formed the most confident key event relationship with the adverse outcome, cholestasis. Other important key events present in the AOP network include: nuclear receptor changes, intracellular bile acid accumulation, bile acid synthesis changes, oxidative stress, inflammation and apoptosis. Conclusions: This process led to the creation of an extensively informative AOP network focused on chemical-induced cholestasis. This optimized AOP network may serve as a mechanistic compass for the development of a battery of in vitro assays to reliably predict chemical-induced cholestatic injury.

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Adverse events associated with the use of cervical manipulation or mobilization and patient characteristics

Cervical spinal manipulation (CSM) and cervical mobilization are frequently used in patients with neck pain and headache. Pre-manipulative cervical instability and arterial integrity tests appear to be unreliable in identifying patients at risk at risk for adverse events. It would be valuable if patients at risk could be identified by specific characteristics during the preliminary screening.

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Adverse events associated with the use of cervical manipulation or mobilization and patient characteristics

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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

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Adverse events after cervical spinal manipulative therapy: consensus based classification and definitions

Cervical spinal manipulations (CSM) are frequently employed techniques to alleviate neck pain and headache. Minor and major complications following CSM have been described, though clear consensus on definition and the classification of the complications had not yet been achieved. As a result, incidence rates may be underestimated. The aim of this study was to develop a consensus-based classification of adverse events following cervical spinal manipulations which has good feasibility in clinical practice and research. Design: A three round Delphi-study. Medical specialists, manual therapists, and patients (n=30) participated in an online survey. In Round 1, participants were invited to select a classification system of adverse events. Potential complications were inventoried and detailed in accordance with the ICF and the ICD-10. In Round 2, panel members categorized the potential complications in their selected classification. During the third round, it was inquired of the participants whether they concurred with the answer of the majority of participants. Results: Thirty four complications were defined. Consensus was achieved for 29 complications for all durations [hours, days, weeks]. For the remaining five complications, consensus was reached for two of the three durations [hours, days, weeks]. Conclusions: A consensus-based classification system of adverse events after cervical spinal manipulation was developed which comprises patients’ and clinicians’ perspectives and has only a small number of categories. The classification system includes a precise description of potential adverse events and is based on international accepted classifications (ICD-10 and ICF). This classification system may be useful for utilization in both clinical practice and research.

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Adverse events after cervical spinal manipulative therapy: consensus based classification and definitions

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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.

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

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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.

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Onset and transition of and recovery from adverse development

Adverse events following cervical manual physical therapy techniques

Prevalence of and relationship between adverse childhood experiences and family context risk factors among children with intellectual disabilities and borderline intellectual functioning

Optimization of an adverse outcome pathway network on chemical-induced cholestasis using an artificial intelligence-assisted data collection and confidence level quantification approach

Adverse events associated with the use of cervical manipulation or mobilization and patient characteristics

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

Adverse events after cervical spinal manipulative therapy: consensus based classification and definitions

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

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

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Rik Kranenburg

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Onset and transition of and recovery from adverse development

Adverse events following cervical manual physical therapy techniques

Prevalence of and relationship between adverse childhood experiences and family context risk factors among children with intellectual disabilities and borderline intellectual functioning

Optimization of an adverse outcome pathway network on chemical-induced cholestasis using an artificial intelligence-assisted data collection and confidence level quantification approach

Adverse events associated with the use of cervical manipulation or mobilization and patient characteristics

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

Adverse events after cervical spinal manipulative therapy: consensus based classification and definitions

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

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

People 1

Rik Kranenburg

Projects 1

Movebite