AOP report: Development of an adverse outcome pathway for deposition of energy leading to cataracts.

Cataracts are one of the leading causes of blindness, with an estimated 95 million people affected worldwide. A hallmark of cataract development is lens opacification, typically associated not only with aging but also radiation exposure as encountered by interventional radiologists and astronauts during the long-term space mission. To better understand radiation-induced cataracts, the adverse outcome pathway (AOP) framework was used to structure and evaluate knowledge across biological levels of organization (e.g., macromolecular, cell, tissue, organ, organism and population). AOPs identify a sequence of key events (KEs) causally connected by key event relationships (KERs) beginning with a molecular initiating event to an adverse outcome (AO) of relevance to regulatory decision-making. To construct the cataract AO and retrieve evidence to support it, a scoping review methodology was used to filter, screen, and review studies based on the modified Bradford Hill criteria. Eight KEs were identified that were moderately supported by empirical evidence (e.g., dose-, time-, incidence-concordance) across the adjacent (directly linked) relationships using well-established endpoints. Over half of the evidence to justify the KER linkages was derived from the evidence stream of biological plausibility. Early KEs of oxidative stress and protein modifications had strong linkages to downstream KEs and could be the focus of countermeasure development. Several identified knowledge gaps and inconsistencies related to the quantitative understanding of KERs which could be the basis of future research, most notably directed to experiments in the range of low or moderate doses and dose-rates, relevant to radiation workers and other occupational exposures.

Deploying elements of scoping review methods for adverse outcome pathway development: a space travel case example.

PURPOSE: Health protection agencies require scientific information for evidence-based decision-making and guideline development. However, vetting and collating large quantities of published research to identify relevant high-quality studies is a challenge. One approach to address this issue is the use of adverse outcome pathways (AOPs) that provide a framework to assemble toxicological knowledge into causally linked chains of key events (KEs) across levels of biological organization to culminate in an adverse health outcome of significance to regulatory decision-making. Traditionally, AOPs have been constructed using a narrative review approach where the collection of evidence that supports each pathway is based on prior knowledge of influential studies that can also be supplemented by individually selecting and reviewing relevant references. OBJECTIVES: We aimed to create a protocol for AOP weight of evidence gathering that harnesses elements of both scoping review methods and artificial intelligence (AI) tools to increase transparency while reducing bias and workload of human screeners. METHODS: To develop this protocol, an existing space-health AOP in the workplan of the Organisation for Economic Co-operation and Development (OECD) AOP Programme was used as a case example. To balance the benefits of both scoping review tools and narrative approaches, a study protocol outlining a screening and search strategy was developed, and three reference collection workflows were tested to identify the most efficient method to inform weight of evidence. The workflows differed in their literature search strategies, and combinations of software tools used. RESULTS: Across the three tested workflows, over 59 literature searches were completed, retrieving over 34,000 references of which over 3300 were human reviewed. The most effective of the three methods used a search strategy with searches across each component of the AOP network, SWIFT Review as a pre-filtering software, and DistillerSR to create structured screening and data extraction forms. This methodology effectively retrieved relevant studies while balancing efficiency in data retrieval without compromising transparency, leading to a well-synthesized evidence base to support the AOP. CONCLUSIONS: The workflow is still exploratory in the context of AOP development, and we anticipate adaptations to the protocol with further experience. To further the systematicity, future iterations of the workflow could include structured quality assessment and risk of bias analysis. Overall, the workflow provides a transparent and documented approach to support AOP development, which in turn will support the need for rigorous methods to identify relevant scientific evidence while being practical to allow uptake by the broader community.

Qualitative evaluation of a postgraduate course in mental health nursing.

This evaluation aimed to explore mental health nurses' experience of one postgraduate (PG) Mental Health Nursing course in Australia. It investigated students' recognition and acquisition of new skills to improve their clinical practice, thereby enhancing consumer and family outcomes. In addition, nurse educators were interviewed to ascertain their impression of the impact of course materials on nursing practice and nurses' confidence in the clinical field. An exploratory qualitative descriptive design was chosen, using semi structured in-depth interviews, to elicit participants' experience of the PG course at completion. Using thematic analysis, themes were extrapolated from the data through examination and reporting on the participant's reaction, learning, behaviour and result of behaviour. The main theme identified was a "new awareness of self" with a number of related sub-themes. The findings from the evaluation indicate that this course supports emerging practitioners to develop a strong professional mental health nursing identity, grounded in recovery oriented practice. The results of this evaluation will inform further development and improvement of postgraduate studies in mental health practice for practice development. Importantly, data indicate a high potential for graduates to lead by example in sharing new knowledge and optimising recovery oriented practice.