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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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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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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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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The Junior Adverse Drug Event Manager (J-ADEM) team is a multifaceted intervention focusing on real-life education for medical students that has been shown to assist healthcare professionals in managing and reporting suspected adverse drug reactions (ADRs) to the Netherlands Pharmacovigilance Centre Lareb. The aim of this study was to quantify and describe the ADRs reported by the J-ADEM team and to determine the clinical potential of this approach. The J-ADEM team consisted of medical students tasked with managing and reporting ADRs in hospitalized patients. All ADRs screened and reported by J-ADEM team were recorded anonymously, and categorized and analysed descriptively. From August 2018 through January 2020, 209 patients on two wards in an academic hospital were screened for ADR events. The J-ADEM team reported 101 ADRs. Although most ADRs (67%) were first identified by healthcare professionals and then reported by the J-ADEM team, the team also reported an additional 33 not previously identified serious ADRs. In 10% of all reported ADRs, the J-ADEM team helped optimize ADR treatment. The ADR reports were largely well-documented (78%), and ADRs were classified as type A (66%), had a moderate or severe severity (85%) and were predominantly avoidable reactions (69%). This study shows that medical students are able to screen patients for ADRs, can identify previously undetected ADRs and can help optimize ADR management. They significantly increased (by 300%) the number of ADR reports submitted, showing that the J-ADEM team can make a valuable clinical contribution to hospital care.
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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 for adverse events. It would be valuable if patients at risk could be identified by specific characteristics during the preliminary screening.Objective was to identify characteristics of 1) patients, 2) practitioners, 3) treatment process and 4) adverse events (AE) occurring after CSM or cervical mobilization.A systematic search was performed in PubMed, Embase, CINAHL, Web-of-science, AMED, and ICL (Index Chiropractic Literature) up to December 2014.Of the initial 1043 studies, 144 studies were included, containing 227 cases. 117 cases described male patients with a mean age of 45 (SD 12) and a mean age of 39 (SD 11) for females. Most patients were treated by chiropractors (66%). Manipulation was reported in 95% of the cases, and neck pain was the most frequent indication. Cervical arterial dissection (CAD) was reported in 57% (P = 0.21) of the cases and 45.8% had immediate onset symptoms. The overall distribution of gender for CAD is 55% (n = 71) for female and therefore opposite of the total AE.Patient characteristics were described poorly. No clear patient profile, related to the risk of AE after CSM, could be extracted. However, women seem more at risk for CAD. There seems to be under-reporting of cases. Further research should focus on a more uniform and complete registration of AE using standardized terminology.
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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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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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Abstract Managing adverse drug reactions (ADRs) is a challenge, especially because most healthcare professionals are insufficiently trained for this task. Since context-based clinical pharmacovigilance training has proven effective, we assessed the feasibility and effect of a creating a team of Junior-Adverse Drug Event Managers (J-ADEMs). The J-ADEM team consisted of medical students (1st–6th year) tasked with managing and reporting ADRs in hospitalized patients. Feasibility was evaluated using questionnaires. Student competence in reporting ADRs was evaluated using a case-control design and questionnaires before and after J-ADEM program participation. From Augustus 2018 to Augustus 2019, 41 students participated in a J-ADEM team and screened 136 patients and submitted 65 ADRs reports to the Netherlands Pharmacovigilance Center Lareb. Almost all patients (n = 61) found it important that “their” ADR was reported, and all (n = 62) patients felt they were taken seriously by the J-ADEM team. Although attending physicians agreed that the ADRs should have been reported, they did not do so themselves mainly because of a “lack of knowledge and attitudes” (50%) and “excuses made by healthcare professionals” (49%). J-ADEM team students were significantly more competent than control students in managing ADRs and correctly applying all steps for diagnosing ADRs (control group 38.5% vs. intervention group 83.3%, p < 0.001). The J-ADEM team is a feasible approach for detecting and managing ADRs in hospital. Patients were satisfied with the care provided, physicians were supported in their ADR reporting obligations, and students acquired relevant basic and clinical pharmacovigilance skills and knowledge, making it a win-win-win intervention.
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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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