Methods for the analysis of histone H3 and H4 acetylation in blood

LBH589 is one of the many histone deacetylase inhibitors (HDACi) that are currently in clinical trial. Despite their wide-spread use, there is little literature available describing the typical levels of histone acetylation in untreated peripheral blood, the treatment and storage of samples to retain optimal measurement of histone acetylation nor methods by which histone acetylation analysis may be monitored and measured during the course of a patient’s treatment. In this study, we have used cord or peripheral blood as a source of human leukocytes, performed a comparative analysis of sample processing methods and developed a flow cytometric method suitable for monitoring histone acetylation in isolated lymphocytes and liquid tumors. Western blotting and immunohistochemistry techniques have also been addressed. We have tested these methods on blood samples collected from four patients treated with LBH589 as part of an Australian Children’s Cancer Clinical Trial (CLBH589AAU03T) and show comparable results when comparing in vitro and in vivo data. This paper does not seek to correlate histone acetylation levels in peripheral blood with clinical outcome but describes methods of analysis that will be of interest to clinicians and scientists monitoring the effects of HDACi on histone acetylation in blood samples in clinical trials or in related research studies

Systematic review of health literacy champions: who, what and how?

Health literacy is an important aspect of equitable, safe, and high-quality care. For organizations implementing health literacy initiatives, using 'change champions' appears to be a promising strategy. This systematic review aimed to identify the empirical and conceptual research that exists about health literacy champions. We conducted the systematic literature search using MEDLINE, Embase, CINAHL, Scopus, and PubMed, with additional studies identified by searching references and citations of included studies and reviews of organizational health literacy. Seventeen articles were included in the final review (case studies, n = 9; qualitative research, n = 4; quasi-experimental, n = 2; opinion articles without case studies, n = 2). Using JBI critical appraisal tools, most articles had a high risk of bias. Often champions were not the focus of the article. Champions included staff across frontline, management, and executive levels. Only five studies described training for champions. Key champion activities related to either (i) increasing organizational awareness and commitment to health literacy, or (ii) influencing organizational strategic and operational planning. The most common output was ensuring that the organization's health information materials met health literacy guidelines. Articles recommended engaging multiple champions at varying levels within the organization, including the executive level. Limited funding and resources were key barriers. Two of four articles reported positive impacts of champions on implementation of health literacy initiatives. Overall, few of the articles described health literacy champions in adequate detail. More comprehensive reporting on this implementation strategy and further experimental and process evaluation research are needed to progress this area of research. This systematic review was registered with PROSPERO (CRD42022348816)

Handling method alters the hedonic value of reward in laboratory mice

Mice are the most widely used model species for drug discovery and scientific research. Consequently, it is important to refine laboratory procedures and practices to ensure high standards of welfare and scientific data quality. Recent studies have identified that the standard practice of handling laboratory mice by their tails increases behaviours indicative of anxiety, which can be overcome by handling mice using a tunnel. However, despite clear negative effects on mice’s behaviour, tunnel handling has yet to be widely implemented. In this study, we provide the first evidence that tail handling also reduces mice’s responses to reward. Anhedonia is a core symptom of clinical depression, and is measured in rodents by assessing how they consume a sucrose solution: depressed mice consume less sucrose and the size of their licking bouts when drinking (their ‘lick cluster sizes’) also tend to be smaller. We found that tail handled mice showed more anhedonic responses in both measures compared to tunnel handled mice, indicative of a decreased responsiveness to reward and potentially a more depressive-like state. Our findings have significant implications for the welfare of laboratory mice as well as the design and interpretation of scientific studies, particularly those investigating or involving reward

Integrating consumer perspectives into a large-scale health literacy audit of health information materials: learnings and next steps.

BACKGROUND: Health information is less effective when it does not meet the health literacy needs of its consumers. For health organisations, assessing the appropriateness of their existing health information resources is a key step to addressing this issue. This study describes novel methods for a consumer-centred large-scale health literacy audit of existing resources and reflects on opportunities to further refine the method. METHODS: This audit focused on resources developed by NPS MedicineWise, an Australian not-for-profit that promotes safe and informed use of medicines. The audit comprised 4 stages, with consumers engaged at each stage: 1) Select a sample of resources for assessment; 2) Assess the sample using subjective (Patient Education Materials Assessment Tool) and objective (Sydney Health Literacy Lab Health Literacy Editor) assessment tools; 3) Review audit findings through workshops and identify priority areas for future work; 4) Reflect and gather feedback on the audit process via interviews. RESULTS: Of 147 resources, consumers selected 49 for detailed assessment that covered a range of health topics, health literacy skills, and formats, and which had varied web usage. Overall, 42 resources (85.7%) were assessed as easy to understand, but only 26 (53.1%) as easy to act on. A typical text was written at a grade 12 reading level and used the passive voice 6 times. About one in five words in a typical text were considered complex (19%). Workshops identified three key areas for action: make resources easier to understand and act on; consider the readers' context, needs, and skills; and improve inclusiveness and representation. Interviews with workshop attendees highlighted that audit methods could be further improved by setting clear expectations about the project rationale, objectives, and consumer roles; providing consumers with a simpler subjective health literacy assessment tool, and addressing issues related to diverse representation. CONCLUSIONS: This audit yielded valuable consumer-centred priorities for improving organisational health literacy with regards to updating a large existing database of health information resources. We also identified important opportunities to further refine the process. Study findings provide valuable practical insights that can inform organisational health actions for the upcoming Australian National Health Literacy Strategy

Helping patient educators meet health literacy needs: End-user testing and iterative development of an innovative health literacy editing tool.

OBJECTIVE: The Sydney Health Literacy Lab (SHeLL) Editor is an online text-editing tool that provides real-time assessment and feedback on written health information (assesses grade reading score, complex language, passive voice). This study aimed to explore how the design could be further enhanced to help health information providers interpret and act on automated feedback. METHODS: The prototype was iteratively refined across four rounds of user-testing with health services staff (N = 20). Participants took part in online interviews and a brief follow-up survey using validated usability scales (System Usability Scale, Technology Acceptance Model). After each round, Yardley's (2021) optimisation criteria guided which changes would be implemented. RESULTS: Participants rated the Editor as having adequate usability (M = 82.8 out of 100, SD = 13.5). Most modifications sought to reduce information overload (e.g. simplifying instructions for new users) or make feedback motivating and actionable (e.g. using frequent incremental feedback to highlight changes to the text altered assessment scores). CONCLUSION: terative user-testing was critical to balancing academic values and the practical needs of the Editor's target users. The final version emphasises actionable real-time feedback and not just assessment. INNOVATION: The Editor is a new tool that will help health information providers apply health literacy principles to written text

Multiple Automated Health Literacy Assessments of Written Health Information: Development of the SHeLL (Sydney Health Literacy Lab) Health Literacy Editor v1.

Producing health information that people can easily understand is challenging and time-consuming. Existing guidance is often subjective and lacks specificity. With advances in software that reads and analyzes text, there is an opportunity to develop tools that provide objective, specific, and automated guidance on the complexity of health information. This paper outlines the development of the SHeLL (Sydney Health Literacy Lab) Health Literacy Editor, an automated tool to facilitate the implementation of health literacy guidelines for the production of easy-to-read written health information. Target users were any person or organization that develops consumer-facing education materials, with or without prior experience with health literacy concepts. Anticipated users included health professionals, staff, and government and nongovernment agencies. To develop this tool, existing health literacy and relevant writing guidelines were collated. Items amenable to programmable automated assessment were incorporated into the Editor. A set of natural language processing methods were also adapted for use in the SHeLL Editor, though the approach was primarily procedural (rule-based). As a result of this process, the Editor comprises 6 assessments: readability (school grade reading score calculated using the Simple Measure of Gobbledygook (SMOG)), complex language (percentage of the text that contains public health thesaurus entries, words that are uncommon in English, or acronyms), passive voice, text structure (eg, use of long paragraphs), lexical density and diversity, and person-centered language. These are presented as global scores, with additional, more specific feedback flagged in the text itself. Feedback is provided in real-time so that users can iteratively revise and improve the text. The design also includes a "text preparation" mode, which allows users to quickly make adjustments to ensure accurate calculation of readability. A hierarchy of assessments also helps users prioritize the most important feedback. Lastly, the Editor has a function that exports the analysis and revised text. The SHeLL Health Literacy Editor is a new tool that can help improve the quality and safety of written health information. It provides objective, immediate feedback on a range of factors, complementing readability with other less widely used but important objective assessments such as complex and person-centered language. It can be used as a scalable intervention to support the uptake of health literacy guidelines by health services and providers of health information. This early prototype can be further refined by expanding the thesaurus and leveraging new machine learning methods for assessing the complexity of the written text. User-testing with health professionals is needed before evaluating the Editor's ability to improve the health literacy of written health information and evaluating its implementation into existing Australian health services

Developing Verbal Health Literacy with Adult Learners Through Training in Shared Decision-Making.

BACKGROUND: Health literacy skills are often assessed in relation to written health materials; however, many important communications are in other formats, especially verbal communication with health care providers. OBJECTIVE: This qualitative study sought to examine adult learners' experiences of developing verbal health literacy skills within an Australian adult basic education program, and to explore verbal communication and shared decision-making as a constituent domain of health literacy. METHODS: We conducted a semi-structured qualitative interview study between September and November 2014 with adult learners who had participated in a single-semester health literacy program that included an integrated shared decision-making component. We analyzed interviews using the Framework method; a matrix-based approach to thematic analysis. A hybrid process of inductive and deductive coding was used to interpret raw data. KEY RESULTS: Interviewees were 22 students from six health literacy classes and ranged in age from 18 to 74 years (mean, 48.3). The majority were women (n = 15) and born outside Australia (n = 13). Health literacy was generally limited according to the Newest Vital Sign screening tool (n = 17). The health literacy program appeared to serve two key functions. First, it stimulated awareness that patients have the right to participate in decision-making concerning their treatment and care. Second, it facilitated verbal skill development across the domains of functional (e.g., communicating symptoms), communicative (e.g., asking questions to extract information about treatment options), and critical (e.g., integrating new knowledge with preferences) health literacy. CONCLUSIONS: Our findings support the conceptualization of health literacy as a modifiable health asset that is subject to change and improvement as a result of deliberate intervention. Results reinforce verbal health literacy as an important component of health literacy, and draw attention to the hierarchy of verbal skills needed for consumers to become more actively involved in decisions about their health. We present a revised model of health literacy based on our findings. [Health Literacy Research and Practice. 2017;1(4):e257-e268.]. PLAIN LANGUAGE SUMMARY: We developed a health literacy program for adults with lower literacy to help learners develop skills to talk to health care providers and share health decisions. The program was taught in Australian adult education settings. The article explores the range of health literacy skills needed for communication and decision-making in this study, and presents a model in which verbal skills are an important part of health literacy

Qualitative insights into the experience of teaching shared decision making within adult education health literacy programmes for lower-literacy learners

© 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd Background: Enhancing health literacy can play a major role in improving healthcare and health across the globe. To build higher-order (communicative/critical) health literacy skills among socially disadvantaged Australians, we developed a novel shared decision making (SDM) training programme for adults with lower literacy. The programme was delivered by trained educators within an adult basic education health literacy course. Objective: To explore the experience of teaching SDM within a health literacy programme and investigate whether communicative/critical health literacy content meets learner needs and teaching and institutional objectives. Design and participants: Qualitative interview study with 11 educators who delivered the SDM programme. Transcripts were analysed using the Framework approach; a matrix-based method of thematic analysis. Results: Teachers noted congruence in SDM content and the institutional commitment to learner empowerment in adult education. The SDM programme was seen to offer learners an alternative to their usual passive approach to healthcare decision making by raising awareness of the right to ask questions and consider alternative test/treatment options. Teachers valued a structured approach to training building on foundational skills, with language reinforcement and take-home resources, but many noted the need for additional time to develop learner understanding and cover all aspects of SDM. Challenges for adult learners included SDM terminology, computational numerical risk tasks and understanding probability concepts. Discussion and conclusions: SDM programmes can be designed in a way that both supports teachers to deliver novel health literacy content and empowers learners. Collaboration between adult education and healthcare sectors can build health literacy capacity of those most in need

Skills for Shared Decision-Making: Evaluation of a Health Literacy Program for Consumers with Lower Literacy Levels.

Background: Shared decision-making (SDM) has been found to be significantly and positively associated with improved patient outcomes. For an SDM process to occur, patients require functional, communicative, and critical health literacy (HL) skills. Objective: This study aimed to evaluate the impact of a program to improve health literacy skills for SDM in adults with lower literacy. Methods: An HL program including an SDM component (HL + SDM) and teaching of the three "AskShareKnow" questions was delivered in adult basic education settings in New South Wales, Australia. The program was evaluated using a partially cluster-randomized controlled trial comparing it to standard language, literacy, and numeracy (LLN) training. We measured the effect of these programs on (1) HL skills for SDM (conceptual knowledge, graphical literacy, health numeracy), (2) types of questions considered important for health decision-making, (3) preferences for control in decision-making, and (4) decisional conflict. We also measured AskShareKnow question recall, use, and evaluation in HL + SDM participants. Key Results: There were 308 participants from 28 classes enrolled in the study. Most participants had limited functional HL (71%) and spoke a language other than English at home (60%). In the primary analysis, the HL + SDM program compared with the standard LLN program significantly increased conceptual knowledge (19.1% difference between groups in students achieving the competence threshold; p = .018) and health numeracy (10.9% difference; p = .032), but not graphical literacy (5.8% difference; p = .896). HL + SDM participants were significantly more likely to consider it important to ask questions that would enable SDM compared to standard LLN participants who prioritized nonmedical procedural questions (all p < .01). There was no difference in preferences for control in decision-making or in decisional conflict. Among HL + SDM participants, 79% (n = 85) correctly recalled at least one of the AskShareKnow questions immediately post-intervention, and 35% (n = 29) after 6 months. Conclusions: Teaching SDM content increased participants' HL skills for SDM and changed the nature of the questions they would ask health care professionals in a way that would enable shared health decisions. [HLRP: Health Literacy Research and Practice. 2019;3(Suppl.):S58-S74.]. Plain Language Summary: We developed a health literacy program that included a shared decision-making (SDM) section. The program was delivered in adult basic education classes by trained educators and compared to standard language, literacy, and numeracy training. Teaching SDM content increased participants' health literacy skills for SDM and changed the nature of the questions they would ask health care professionals

The Readability Study: A Randomised Trial of Health Information Written at Different Grade Reading Levels.

BACKGROUND: Despite increasing attention on health literacy and the inclusion of grade reading level recommendations in guidelines, it remains unclear if lowering the grade reading level of written health information to specific target grades improves patient-related outcomes. OBJECTIVE: To assess whether grade reading level of written information affects knowledge, perceived reading ease, acceptability and trustworthiness of information and, to explore whether information written at a lower grade reading level reduces disparities in outcomes across health literacy levels. DESIGN: We conducted a 4-arm online randomized trial with a community sample of adults living in Australia from 31 July to 20 September 2023. EXPERIMENTAL ARMS: Participants were randomised to one of four arms: Information about sciatica and knee osteoarthritis written at a grade 8, 10, 12 or 14 reading level. Readability was assessed using the SMOG Index and iteratively revised to each lower grade. MEASURES: Primary outcome was knowledge of health conditions. Secondary outcomes were brief knowledge, perceived reading ease, acceptability (i.e., perceived usefulness and likelihood to recommend) and trustworthiness of information. RESULTS: 2235 participants were randomised and included in the analysis. Mean age was 41 years and 54.5% identified as female. Low health literacy was identified in 28.2% of participants. We found no evidence of a main effect of grade reading level on knowledge (grade 8: 9.0 (SD = 2.7), grade 10: 9.1 (SD = 2.6), grade 12: 8.9, grade 14: 9.1 (SD = 2.7). Participants with high health literacy had higher knowledge scores overall, however, there was no evidence that health literacy modified the effect of grade reading level. There were no significant differences in any of the secondary outcomes. CONCLUSIONS: Our study showed no difference in knowledge when grade reading level was manipulated alone. Our findings indicate there is limited value in reducing grade reading level without attention to other health literacy principles. ANZCTR TRIAL REGISTRY NUMBER: ACTRN12623000224628p