Clinical, experimental and pathophysiological effects of Yaq-001: a non-absorbable, gut-restricted adsorbent in models and patients with cirrhosis.

OBJECTIVE: Targeting bacterial translocation in cirrhosis is limited to antibiotics with risk of antimicrobial resistance. This study explored the therapeutic potential of a non-absorbable, gut-restricted, engineered carbon bead adsorbent, Yaq-001 in models of cirrhosis and acute-on-chronic liver failure (ACLF) and, its safety and tolerability in a clinical trial in cirrhosis. DESIGN: Performance of Yaq-001 was evaluated in vitro. Two-rat models of cirrhosis and ACLF, (4 weeks, bile duct ligation with or without lipopolysaccharide), receiving Yaq-001 for 2 weeks; and two-mouse models of cirrhosis (6-week and 12-week carbon tetrachloride (CCl4)) receiving Yaq-001 for 6 weeks were studied. Organ and immune function, gut permeability, transcriptomics, microbiome composition and metabolomics were analysed. The effect of faecal water on gut permeability from animal models was evaluated on intestinal organoids. A multicentre, double-blind, randomised, placebo-controlled clinical trial in 28 patients with cirrhosis, administered 4 gr/day Yaq-001 for 3 months was performed. RESULTS: Yaq-001 exhibited rapid adsorption kinetics for endotoxin. In vivo, Yaq-001 reduced liver injury, progression of fibrosis, portal hypertension, renal dysfunction and mortality of ACLF animals significantly. Significant impact on severity of endotoxaemia, hyperammonaemia, liver cell death, systemic inflammation and organ transcriptomics with variable modulation of inflammation, cell death and senescence in the liver, kidneys, brain and colon was observed. Yaq-001 reduced gut permeability in the organoids and impacted positively on the microbiome composition and metabolism. Yaq-001 regulated as a device met its primary endpoint of safety and tolerability in the clinical trial. CONCLUSIONS: This study provides strong preclinical rationale and safety in patients with cirrhosis to allow clinical translation. TRIAL REGISTRATION NUMBER: NCT03202498.

What is the relationship between raising the minimum legal sales age of tobacco above 20 and cigarette smoking? A systematic review.

INTRODUCTION: There is considerable interest in raising the age of sale of tobacco above the conventional age of 18. We systematically reviewed whether raising the minimum legal sales age of tobacco (MLSA) to 20 or above is associated with reduced prevalence of smoking compared to an MLSA set at 18 or below. METHODS: Following a pre-registered protocol on PROSPERO (ref: CRD42022347604), six databases of peer-reviewed journals were searched from January 2015 to April 2024. Backwards and forwards reference searching was conducted. Included studies assessed the association between MLSAs ≥20 with cigarette smoking or cigarette sales for those aged 11-20. Assessments on e-cigarettes were excluded. Pairs of reviewers independently extracted study data. We used ROBINS-I to assess risk of bias and GRADE to assess quality of evidence. Findings were also synthesised narratively. RESULTS: 23 studies were reviewed and 34 estimates of association were extracted. All extracted studies related to Tobacco 21 laws in the United States. Moderate quality evidence was found for reduced cigarette sales, moderate quality evidence was found for reduced current smoking for 18 - 20 year olds, and low quality evidence was found for reduced current smoking for 11 - 17 year olds. The positive association was stronger for those with lower education. Study bias was variable. CONCLUSIONS: There is moderate quality evidence that Tobacco 21 can reduce overall cigarette sales and current cigarette smoking amongst those aged 18- 20. It has potential to reduce health inequalities. Research in settings other than the United States is required. IMPLICATIONS: This systematic review on raising the minimum legal sale age of tobacco to 20 or above demonstrates there is moderate quality evidence that such laws reduce cigarette sales, and moderate quality evidence they reduce smoking prevalence amongst those aged 18-20 compared to a minimum legal sale age of 18 or below. The research highlights potential benefits in reducing health inequalities, especially individuals from lower educational backgrounds. Studies are limited to the United States, highlighting a need for more global research to assess the impact of these policies in other settings.

Attitudes And Exposure To Illicit Tobacco In England, 2022.

INTRODUCTION: The UK has achieved reductions in illicit tobacco (IT) market size and share. However, there remains a 17.7% tobacco duty gap, contributing to health inequalities. In January 2024, the UK government announced a new strategy to control IT, along with provision of new funding. METHODS: A representative cross-sectional survey of adults in England ran in April 2022 to evaluate attitudes and exposure to IT. Tobacco smokers were asked questions about encounters with IT, while all participants answered questions on knowledge and perspectives on IT. RESULTS: Of 262 tobacco smokers, 18.3% (95% CI 13.8% - 23.6%) had come across IT in the past year. Men had four times the odds of encountering IT recently than women. Among 1,767 adults responding to questions on IT, two-thirds agreed IT harmed children, and more than half agreed IT was linked to organised crime. Younger adults, smokers and those in lower socio-economic groups were less likely to agree IT was harmful. CONCLUSIONS: Exposure to IT, especially among younger males, remains a concern. While most of the public acknowledge its harm, this is not universal, and some population groups are less likely to do so. IMPLICATIONS: The study highlights persistent exposure to illicit tobacco in England, especially among younger males, and varying perceptions of illicit tobacco harm across socio-economic groups. Tackling illicit tobacco requires collaboration between health and enforcement agencies, independent of the tobacco industry's influence. Strategies should include components that shift demand for illicit tobacco and denormalise its presence in communities, particularly in lower socio-economic areas with higher smoking prevalence.

Non-Pharmacological Interventions in the Management of Dementia-Related Psychosis: A Systematic Review and Meta-Analysis.

OBJECTIVE: As populations age globally, there is an increasing prevalence of dementia, with an estimated 153 million living with dementia by 2050. Up to 70% of people with dementia experience dementia-related psychosis (D-RP). Antipsychotic medications are associated with many adverse effects in older people. This review aims to evaluate the evidence of non-pharmacological interventions in managing D-RP. METHOD: The search of Medline, EMBASE, Web of Science, CINAHL, PsycINFO, and Cochrane included randomised controlled trials that evaluated non-pharmacological interventions. Data extraction and assessment of quality were assessed independently by two researchers. Heterogenous interventions were pooled using meta-analysis. RESULTS: A total of 18 articles (n = 2040 participants) were included and categorised into: sensory-, activity-, cognitive- and multi-component-orientated. Meta-analyses showed no significant impact in reducing hallucinations or delusions but person-centred care, cognitive rehabilitation, music therapy, and robot pets showed promise in single studies. CONCLUSIONS AND IMPLICATIONS: Future interventions should be developed and evaluated with a specific focus on D-RP as this was not the aim for many of the included articles.

Experiences of family carers supporting older people within the last year of life in rural and remote areas in the UK.

BACKGROUND: In the UK, a large proportion of older adults live in rural/remote locations. More people are dying at home and require care from their families. Little is known about the experiences of family carers of older people in rural/remote areas in the last year of life. AIM: To explore the experiences of current and bereaved family carers who support/ed an older person in a rural area in the UK towards the end-of-life. DESIGN: Qualitative methodology using semi-structured interviews and reflexive thematic analysis methods. METHOD: Interviews were conducted with family carers of rural/remote-dwelling older people in the last year of life. Participants were recruited through national support services, third sector organisations and social media. RESULTS: Interviews were conducted with 20 family carers. Most were female (n = 17) and aged 52-80 years. Family carers experienced difficulties in accessing health and social care in rural/remote areas due to workforce and skills shortages within their regions. The wider community helped with practical tasks and made carers feel less alone. Community-based services, such as day care, helped to provide respite for carers and promoted meaningful activity and social inclusion for older people. Although internet access was problematic, family carers gained support remotely via social media and telehealth services. CONCLUSION: Family carers of older people in the last year of life in rural/remote areas value support from the wider community. Further work is required to understand how Public Health approaches to palliative care and workforce distribution can support rural/remote carers and older people.

Factors associated with self-rated health in people with late-stage parkinson's and cognitive impairment.

PURPOSE: To investigate the contributors to self-rated health in people with late-stage Parkinson's disease (PD) and cognitive impairment. METHODS: A secondary analysis of baseline data from the international Care of Late-Stage Parkinsonism (CLaSP) cohort study was conducted. Participants with PD and either dementia or mild cognitive impairment or MMSE < 24/30 in the absence of major depression were included if they had completed the EQ-5D-3L assessment (n = 277). Factors associated with self-rated health (EQ-5D-3L Index and Visual Analogue Scale) were investigated through multivariable linear regression. RESULTS: More severe PD (motor and non-motor) was associated with worse self-rated health. The EQ-5D-3L dimensions of Mobility, Self-Care and Usual Activities were almost universally affected; the latter two particularly severely. Being unable to perform usual activities or having moderate to extreme anxiety or depression were significantly associated with EQ-5D-3L Visual Analogue Scale, suggesting these are particularly valued. Worse motor impairment and function and the non-motor symptom domains of mood, perception, sexual function, and miscellaneous (e.g., pain) were associated with worse self-rated health, whereas greater burden of gastrointestinal symptoms was associated with better self-rated health in multivariate analysis. Better self-rated health was associated with recent PD nurse consultation, and higher doses of dopaminergic medication. CONCLUSION: Improvement of activities of daily living, mood and anxiety should be prioritised in clinical practice, with consideration of perception and sexual function in this population. Recent nurse consultations and higher antiparkinsonian doses are associated with better self-rated health, suggesting there is no room for a therapeutic nihilism in this population of people within a complex phase of PD.

A palliative care goals model for people with dementia and their family: Consensus achieved in an international Delphi study.

BACKGROUND: Advance care planning in dementia includes supporting the person and their family to consider important goals of care. International research reports the importance of psycho-social-spiritual aspects towards end of life. AIM: To develop a multidimensional international palliative care goals model in dementia for use in practice. DESIGN: International Delphi study integrating consensus and evidence from a meta-qualitative study. The Delphi panel rated statements about the model on a 5-point agreement scale. The criteria for consensus were pre-specified. SETTING/PARTICIPANTS: Seventeen researchers from eight countries developed an initial model, and 169 candidate panellists were invited to the international online Delphi study. RESULTS: Panellists (107; response 63.3%) resided in 33 countries. The model comprised four main care goals: (1) Comfort ensured; (2) Control over function maintained; (3) Identity protected and personhood respected and (4) Coping with grief and loss-person and caregiver supported. The model reflects how needs and care goals change over time with the progression of dementia, concluding with bereavement support. The first version of the model achieved a consensus after which it was slightly refined based on feedback. We did not achieve a consensus on adding a goal of life prolongation, and on use of the model by people with dementia and family themselves. CONCLUSION: A new palliative care goals model for people with dementia and their families includes relationship aspects for use by professionals and achieved a consensus among a panel with diverse cultural background. The position of life prolongation in relation to palliative care goals needs further research.

Co-design of the EMBED-Care Framework as an intervention to enhance shared decision-making for people affected by dementia and practitioners, comprising holistic assessment, linked with clinical decision support tools: A qualitative study.

INTRODUCTION: Shared decision-making intends to align care provision with individuals' preferences. However, the involvement of people living with dementia in decision-making about their care varies. We aimed to co-design the EMBED-Care Framework, to enhance shared decision-making between people affected by dementia and practitioners. METHODS: A theory and evidence driven co-design study was conducted, using iterative workshops, informed by a theoretical model of shared decision-making and the EMBED-Care Framework (the intervention) for person-centred holistic palliative dementia care. The intervention incorporates a holistic outcome measure for assessment and review, linked with clinical decision-support tools to support shared decision-making. We drew on the Medical Research Council (MRC) guidance for developing and evaluating complex interventions. Participants included people with dementia of any type, current or bereaved family carers and practitioners. We recruited via established dementia groups and research and clinical networks. Data were analysed using reflexive thematic analysis to explore how and when the intervention could enhance communication and shared decision-making, and the requirements for use, presented as a logic model. RESULTS: Five co-design workshops were undertaken with participants comprising people affected by dementia (n = 18) and practitioners (n = 36). Three themes were generated, comprising: (1) 'knowing the person and personalisation of care', involving the person with dementia and/or family carer identifying the needs of the person using a holistic assessment. (2) 'engaging and considering the perspectives of all involved in decision-making' required listening to the person and the family to understand their priorities, and to manage multiple preferences. (3) 'Training and support activities' to use the Framework through use of animated videos to convey information, such as to understand the outcome measure used to assess symptoms. CONCLUSIONS: The intervention developed sought to enhance shared decision-making with individuals affected by dementia and practitioners, through increased shared knowledge of individual priorities and choices for care and treatment. The workshops generated understanding to manage disagreements in determining priorities. Practitioners require face-to-face training on the intervention, and on communication to manage sensitive conversations about symptoms, care and treatment with individuals and their family. The findings informed the construction of a logic model to illustrate how the intervention is intended to work.

Acceptability of Using a Decision Aid to Support Family Carers of People With Dementia Towards the End of Life: A Qualitative Study.

OBJECTIVES: To explore the experiences, acceptability and utility of a decision aid for family carers of people with dementia towards the end of life. METHODS: We conducted semi-structured interviews with a sample of family carers enroled into a 6-month feasibility study in England, sampling to gain a range of experiences and views, based on relationship to person they cared for (e.g., spouse, adult child), age, gender, and self-reported use of the decision aid during the feasibility study. Interviews were conducted in March 2021-July 2021 and analysed using reflexive thematic analysis. We used COREQ checklist to report our methods and results. RESULTS: Family carers found the decision aid acceptable, describing it as comprehensive, accessible with relevant information and its presentation enabled good engagement. Experiences of the decision aid covered four main themes which demonstrated the perceived acceptability and utility: 1. A source of support and reassurance; 2. Empowering conversations and confidence; 3. Including the person living with dementia; and 4. Breaking down complexity. CONCLUSIONS: An aid focussing on decisions about dementia end of life care supported family carers break down complex and emotive decisions, not only with making decisions in the moment but also in future planning. PATIENT OR PUBLIC CONTRIBUTION: Our three Patient and Public Involvement (PPI) members (all former family carers) were crucial throughout the wider study. PPI supported development of the topic guides, supported trialling the topic guide and interview procedures and finally supported the development of themes as part of the analysis.

Compound impact of cognitive and physical decline: A qualitative interview study of people with Parkinson's and cognitive impairment, caregivers and professionals.

BACKGROUND: Cognitive impairment is common in Parkinson's disease and is associated with poorer quality of life and increased caregiver distress, but little qualitative information is available on lived experiences of people with Parkinson's who also have cognitive impairment. OBJECTIVES: The aim of this study was to explore the challenges of cognitive impairment in Parkinson's, triangulating the perspectives of people with Parkinson's, caregivers and healthcare professionals. METHODS: Semistructured interviews were conducted with 11 people with Parkinson's and cognitive impairment, 10 family caregivers and 27 healthcare professionals, using purposive sampling in the United Kingdom (2019-2021). Cognitive impairment was identified by healthcare professionals and required subjective symptoms. Relevant cognitive diagnoses were recorded. Interviews were audio-recorded, transcribed and analysed using reflexive thematic analysis. RESULTS: An overarching concept of the compound impact of cognitive and physical decline was developed, with six themes. Four themes describe the experience of living with cognitive impairment in Parkinson's: (1) Challenges in Daily Activities, (2) Psychological Impact and (3) Evolving Communication Difficulties together contributing to (4) Social Shift, encompassing a reduction in wider social activities but intensification of close relationships with increased dependence. A fifth theme (5) Living Well describes positive influences on these experiences, encompassing intrinsic motivation, self-management strategies and supportive relationships. Furthermore, underlying and shaping the whole experience was the sixth theme: (6) Preconceptions about Cognitive Impairment, describing fear and denial of symptoms and poor understanding of the nature of cognitive impairment in Parkinson's, with differences to other dementia pathologies. CONCLUSIONS: Cognitive impairment superimposed on the existing challenges of Parkinson's has a multifaceted impact and makes living with the condition arduous. Increased understanding of the experiences of this group and employing the identified facilitators for living well may be able to improve patient and caregiver experiences. PATIENT OR PUBLIC CONTRIBUTION: Two people with Parkinson's and cognitive impairment and three caregivers contributed to the study. Between them they contributed throughout the entirety of the project, giving input at conceptualisation as well as advice and review of interview questions, participant information leaflets, recruitment, interpretation of findings and summaries of the project.

Barriers and facilitators of self-management of diabetes amongst people experiencing socioeconomic deprivation: A systematic review and qualitative synthesis.

BACKGROUND: The number of people living with diabetes is rising worldwide and a higher prevalence of diabetes has been linked to those experiencing socioeconomic deprivation. Self-management strategies are vital and known to reduce the risks of long-term complications amongst people living with diabetes. Lack of knowledge about self-care activity required to manage diabetes is a key barrier to successful self-management. Self-management interventions can be less effective in socioeconomically deprived populations which can increase the risk of exacerbating health inequalities. The purpose of this review is to identify and synthesise qualitative evidence on the barriers and facilitators of self-management of diabetes amongst people who are socioeconomically disadvantaged. METHODS: MEDLINE, EMBASE, AMED, PsycINFO and CINAHL Plus were searched for qualitative studies concerning self-management of multiple long-term conditions amongst socioeconomically disadvantaged populations. Relevant papers which focused on diabetes were identified. Data were coded and thematically synthesised using NVivo. FINDINGS: From the search results, 79 qualitative studies were identified after full-text screening and 26 studies were included in the final thematic analysis. Two overarching analytical themes were identified alongside a set of subthemes: (1) Socioeconomic barriers to diabetes self-management; healthcare costs, financial costs of healthy eating, cultural influences, living in areas of deprivation, competing priorities and time constraints, health literacy, (2) facilitators of diabetes self-management; lifestyle and having goals, support from healthcare providers, informal support. DISCUSSION: Self-management of diabetes is challenging for people experiencing socioeconomic deprivation due to barriers associated with living in areas of deprivation and financial barriers surrounding healthcare, medication and healthy food. Support from healthcare providers can facilitate self-management, and it is important that people with diabetes have access to interventions that are designed to be inclusive from a cultural perspective as well as affordable. PATIENT OR PUBLIC CONTRIBUTION: A patient advisory group contributed to the research questions and interpretation of the qualitative findings by reflecting on the themes developed.

A qualitative exploration of the barriers and facilitators to self-managing multiple long-term conditions amongst people experiencing socioeconomic deprivation.

BACKGROUND: Globally, it is estimated that one in three adults live with two or more long-term conditions (multiple long-term conditions, MLTCs), that require self-management. People who experience socioeconomic deprivation face significant health inequalities due to a range of interrelated characteristics that lead to a lack of resources and opportunities. Previous research with underserved populations indicate low levels of trust towards primary care providers and potential barriers for developing patient-healthcare professional relationships. The purpose of this paper is to explore the barriers and facilitators to self-managing MLTCs, amongst people who experience socioeconomic deprivation. METHODS: Semistructured one-to-one interviews with adults (n = 28) living in London and Sheffield, United Kingdom with MLTCs who are experiencing socioeconomic deprivation. Participants were recruited through general practices, community channels and social media. Data were analysed in NVivo using reflexive thematic analysis methods. FINDINGS: Four analytical themes were developed: (1) challenges in accessing healthcare services, financial assistance, and cultural awareness; (2) empowerment and disempowerment through technology, including digital exclusion, and use of technology; (3) impact and causes of exclusion on self-management, including social isolation, area-based and economic exclusion, and health-related stigma and (4) adapting self-management strategies, including cost-effective, and culturally/lifestyle appropriate strategies. CONCLUSIONS: Future health interventions and services need to be developed with consideration of the combined complexities of managing MLTCs while experiencing socioeconomic deprivation. Increased awareness in practitioners and commissioners of the complexities surrounding the lives of people experiencing socioeconomic deprivation, and the need for targeted strategies to promote self-management of MLTCs are of great importa. PATIENT OR PUBLIC CONTRIBUTION: A patient advisory group contributed to all stages of the study, including providing important feedback on study documents (topic guides and recruitment materials), as well as providing critical insights surrounding the interpretation of interview data.

Co-Designing a Palliative Dementia Care Framework to Support Holistic Assessment and Decision Making: The EMBED-Care Framework.

BACKGROUND: People with dementia have complex palliative care needs that are often unmet, including physical and psycho-social needs. It is essential to empower people with dementia, family carers and professionals to better assess and manage care needs. We aimed to co-design a palliative dementia care Framework delivered through a digital app to support holistic assessment and decision making for care in the community and care homes-the EMBED-Care Framework. METHODS: A systematic co-design approach was adopted to develop the EMBED-Care Framework across three stages: 1) Framework analysis to synthesise data from preceding evidence reviews, large routine clinical data and cohort studies of unmet palliative dementia care need; 2) Co-design using iterative workshops with people with dementia, family carers and health and social care professionals to construct the components, design of the app and implementation requirements; and 3) User testing to refine the final Framework and app, and strengthen use for clinical practice and methods of evaluation. RESULTS: The Framework was co-designed for delivery through an app delivered by aTouchAway. It comprised five main components: 1) holistic assessment of palliative care needs using the Integrated Palliative care Outcome Scale-Dementia (IPOS-Dem); 2) alert system of IPOS-Dem scores to highlight unmet needs; 3) IPOS-Dem scores and alerts enable shared decision making between the practitioner, patient and/or carer to support priority setting and goals of care; 4) evidence-informed clinical decision support tools automatically linked with identified needs to manage care; and 5) Training package for users incorporating face-to-face sessions, clinical champions who received additional face-to-face sessions, animated videos and manual covering the main intervention components and email and telephone support from the research team. CONCLUSIONS: This is a novel digital palliative dementia care intervention to link holistic assessment with clinical decision support tools that are practical and easy to use but address the complexity of palliative dementia care. The Framework is ready for feasibility testing and pilot studies for people with dementia residing at home or in a care home. PATIENT OR PUBLIC CONTRIBUTION: We were guided by our Patient and Public Involvement (PPI) group consisting of three people with mild dementia, including younger onset dementia, and seven family carers throughout the project. They supported the overall development of the Framework, including planning of workshops, interpreting findings and testing the framework in our PPI meetings.

Intervention components in the self-management of Parkinson's: a mixed-methods synthesis of qualitative and quantitative evidence.

INTRODUCTION: Self-management interventions consist of multiple components to support people in the management of medical, emotional, and behavioural aspects of their condition, and aim to improve quality of life, function, and other outcomes. A systematic review of self-management interventions in Parkinson's showed no conclusive evidence for effectiveness of specific self-management approaches in Parkinson's to date but identified several potentially useful components. AIM: To identify the key required components for self-management in people with Parkinson's by synthesising evidence from a body of primary qualitative evidence and systematic reviews, and to explore which of these key components should be incorporated into trials of self-management in Parkinson's. METHOD: A mixed-methods synthesis was conducted. We combined data from two primary qualitative studies and a systematic review of qualitative studies that focused on self-management in Parkinson's to identify key intervention components. These were then mapped onto the results of a systematic review of Randomised Controlled Trials (RCTs) using matrices. First, data were extracted from the qualitative studies with people with Parkinson's and healthcare professionals on the key self-management components in this population. Second, a matrix table was created to map the identified Parkinson's specific self-management components against potential effectiveness from published RCTs of self-management interventions. RESULTS: Synthesis of qualitative data identified 15 potential self-management components. These 15 components included components needed to start self-managing (e.g., information, skill acquirement) and components needed to maintain self-managing (e.g., self-motoring, increasing motivation). From 18 RCTs, interventions varied in how many components were included (range 1-10). Trials reporting significant beneficial effects of their intervention included a higher number of components (4 or more self-management components) than trials without significant findings (1-3 self-management components). CONCLUSION: Fifteen key self-management components were identified that should be incorporated into interventions or programs of self-management in Parkinson's. No current trial has incorporated all aspects, but a higher number of these key components appears to make trials of self-management interventions more likely to be successful.

ChatGPT sits the DFPH exam: large language model performance and potential to support public health learning.

BACKGROUND: Artificial intelligence-based large language models, like ChatGPT, have been rapidly assessed for both risks and potential in health-related assessment and learning. However, their applications in public health professional exams have not yet been studied. We evaluated the performance of ChatGPT in part of the Faculty of Public Health's Diplomat exam (DFPH). METHODS: ChatGPT was provided with a bank of 119 publicly available DFPH question parts from past papers. Its performance was assessed by two active DFPH examiners. The degree of insight and level of understanding apparently displayed by ChatGPT was also assessed. RESULTS: ChatGPT passed 3 of 4 papers, surpassing the current pass rate. It performed best on questions relating to research methods. Its answers had a high floor. Examiners identified ChatGPT answers with 73.6% accuracy and human answers with 28.6% accuracy. ChatGPT provided a mean of 3.6 unique insights per question and appeared to demonstrate a required level of learning on 71.4% of occasions. CONCLUSIONS: Large language models have rapidly increasing potential as a learning tool in public health education. However, their factual fallibility and the difficulty of distinguishing their responses from that of humans pose potential threats to teaching and learning.

Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. METHODS: Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). RESULTS: There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelial function [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002) improved significantly in the DIALIVE group. CONCLUSIONS: These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. IMPACT AND IMPLICATIONS: This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. CLINICAL TRIAL NUMBER: NCT03065699.

A shared decision-making model about care for people with severe dementia: A qualitative study based on nutrition and hydration decisions in acute hospitals.

OBJECTIVES: To understand the decision-making processes regarding eating and drinking for hospital patients with severe dementia and use this data to modify a decision-making model about care for people with severe dementia. METHODS: From January to May 2021, qualitative semi-structured interviews were conducted with 29 family carers and hospital staff in England who cared for people with severe dementia during hospital admissions. Interviews were transcribed verbatim and analysed using codebook thematic analysis. RESULTS: We demonstrated a modified decision-making model consisting of six stages of the decision-making process: (i) identify a decision to be made; (ii) exchange information and recognise emotions; (iii) clarify values and preferences of all involved; (iv) consider feasibility of each choice; (v) share preferred choice and make a final decision; and (vi) deliver the decision, monitor outcomes and renegotiation. From this study, decision-making needed to be shared among all people involved and address holistic needs and personal values of people with dementia and family carers. However, hospital staff often made assumptions about the persons' ability to eat and drink without adequate consultation with family carers. The process was impacted by ward culture, professional practice, and legal framework, which might overlook cultural and personal beliefs of the persons and families. Treatment escalation plans could help inform stepwise treatments, create realistic expectations, and guide future decisions. CONCLUSIONS: Our decision-making model provides clear stages of decision-making processes and can be used to guide clinical practice and policy around care decisions for eating and drinking, which is often poorly supported.

Muslim women's views and experiences of family planning in Saudi Arabia: a qualitative study.

BACKGROUND: Islamic beliefs are associated with decreased contraceptive use compared to other religions, and Muslim women's contraceptive needs are often unmet. Research is needed to provide an in-depth understanding of the complex set of barriers to Muslim women's contraceptive use. Therefore, we aimed to explore Muslim women's awareness and experiences with family planning in Saudi Arabia and investigate barriers to contraceptive use and access to family planning. METHODS: A qualitative study using semi-structured interviews with women in a public hospital, in Riyadh, Saudi Arabia, between January and June 2019. Data was analysed using reflexive thematic analysis. RESULTS: Twenty-eight women participated in the study. Women's contraceptive awareness was limited to two methods. Women expressed positive attitudes towards family planning and did not believe it is forbidden in Islam. Barriers to contraception use included lack of knowledge, misconceptions, fear of side effects, family and community and social norms. Many women expressed that they have the right to use contraception, even if their husbands disapprove. Our findings show that healthcare providers rarely offered contraceptive advice, even when requested. Healthcare providers often prescribe oral contraceptives without offering information on other methods available. CONCLUSION: Our findings suggest that education plays a fundamental role in reproductive autonomy. Men's role in family planning should be encouraged through sharing reproductive responsibility and supporting women's contraceptive choices. Efforts should be directed towards improving women's awareness of different methods of contraception.

The Pregnancy Rescue Case: a reply to Hendricks.

In 'The Pregnancy Rescue Case: why abortion is immoral', Hendricks presents The Pregnancy Rescue Case. In this reply I argue that even if it would be better (i.e., less bad) for the abortion to be prevented in The Pregnancy Rescue Case, that does not mean that typical abortions are impermissible. I also argue that there is a possible explanation, consistent with the pro-choice view and empirically testable, as to why people would think it better for the abortion to be prevented in The Pregnancy Rescue Case.

Effectiveness of self-management interventions for long-term conditions in people experiencing socio-economic deprivation in high-income countries: a systematic review and meta-analysis.

BACKGROUND: Long-term conditions (LTCs) are prevalent in socio-economically deprived populations. Self-management interventions can improve health outcomes, but socio-economically deprived groups have lower participation in them, with potentially lower effectiveness. This review explored whether self-management interventions delivered to people experiencing socio-economic deprivation improve outcomes. METHODS: We searched databases up to November 2022 for randomized trials. We screened, extracted data and assessed the quality of these studies using Cochrane Risk of Bias 2 (RoB2). We narratively synthesized all studies and performed a meta-analysis on eligible articles. We assessed the certainty of evidence using GRADE for articles included in the meta-analysis. RESULTS: The 51 studies included in this review had mixed findings. For the diabetes meta-analysis, there was a statistically significant pooled reduction in haemoglobin A1c (-0.29%). We had moderate certainty in the evidence. Thirty-eight of the study interventions had specific tailoring for socio-economically deprived populations, including adaptions for low literacy and financial incentives. Each intervention had an average of four self-management components. CONCLUSIONS: Self-management interventions for socio-economically deprived populations show promise, though more evidence is needed. Our review suggests that the number of self-management components may not be important. With the increasing emphasis on self-management, to avoid exacerbating health inequalities, interventions should include tailoring for socio-economically deprived individuals.