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Summary: Little is known of the scale of avoidable injuries presenting to medical services on a national level in the UK. This study aimed to assess the type and incidence of preventable wrist and hand injuries (as defined by the core research team) at a national level in the UK. 28 UK hospitals undertook a service evaluation of all hand trauma cases presenting to their units over a 2 week period in early 2021 identifying demographical and aetiological information about injuries sustained. 1909 patients were included (184 children) with a median age of 40 (IQR 25-59) years. The commonest five types of injury were fractures of the wrist; single phalangeal or metacarpal fractures; fingertip injuries; and infection, with the most common mechanisms being mechanical falls and manual labour. This is the first extensive survey of preventable hand injuries in the UK, identifying a need for further work into prevention to reduce healthcare burden and cost. 50% of injuries presenting to hand surgeons are preventable, with the most common injuries being single fractures of the wrist, phalanx and metacarpal. Few preventable injuries were related to alcohol or narcotic intoxication. Further research is needed to identify how to initiate injury prevention measures for hand injuries, particularly focussed towards hand fracture prevention.

Abstract Background Acute hospital wards can be difficult places for many people living with dementia. Promoting comfort and wellbeing can be challenging in this environment. There is little evidence‐based support for professionals working on acute care wards on how to respond to distress and maximise comfort and wellbeing among patients living with dementia. Objectives Our overall aim was to codesign an evidence‐based easy‐to‐use heuristic decision‐support framework, which was acceptable and practical but acknowledges the complex and acute nature of caring for patients with dementia in the hospital. This paper presents the development process and resulting framework. Methods A codesign study was informed by data from (1) a literature review of the care and management of people living with dementia in acute hospitals; (2) a cohort study of comfort and discomfort in people with dementia in acute hospitals; and (3) interviews with family carers and health care professionals. We synthesised evidence from these data sources and presented to key stakeholders through codesign meetings and workshops to produce our decision‐support framework. Results The framework consists of a series of flowcharts and operates using a three‐stage process of: (1) assess comfort/discomfort; (2) consider causes of discomfort; and (3) address patient needs to manage the discomfort. Conclusion Working with key stakeholders, synthesising diverse quantitative and qualitative evidence to build a clinical framework is a feasible approach to help address the needs of patients living with dementia in an acute hospital setting. The result is a framework which is now ready for evaluation and implementation. Patient and Public Contribution We worked closely with people living with dementia and family carers throughout this study, including the development of the study protocol with input on study development and design, through to inclusion in stakeholder workshops and codesign of the decision support framework.

Abstract Background Dementia leads to multiple issues including difficulty in communication and increased need for care and support. Discussions about the future often happen late or never, partly due to reluctance or fear. In a sample of people living with dementia and carers, we explored their views and perceptions of living with the condition and their future. Methods Semi-structured interviews were conducted in 2018-19 with 11 people living with dementia and six family members in England. Interviews were audio-recorded, transcribed and analysed using reflexive thematic analysis. Results Findings were explored critically within the theory of social death and three themes were developed: (1) loss of physical and cognitive functions, (2) loss of social identity, and (3) social connectedness. Most participants living with dementia and carers wanted to discuss the present, rather than the future, believing a healthy lifestyle would prevent the condition from worsening. Those with dementia wanted to maintain control of their lives and demonstrated this by illustrating their independence. Care homes were often associated with death and loss of social identity. Participants used a range of metaphors to describe their dementia and the impact on their relationships and social networks. Conclusion Focusing on maintaining social identity and connectedness as part of living well with dementia may assist professionals in undertaking advance care planning discussions.

Abstract Introduction COVID‐19 has disproportionately affected people living with dementia and their carers. Its effects on health and social care systems necessitated a rapid‐response approach to care planning and decision‐making in this population, with reflexivity and responsiveness to changing individual and system needs at its core. Considering this, a decision‐aid to help families of persons with dementia was developed. Objectives To coproduce with people living with dementia, and the people who care for them, a decision‐aid for family carers of people living with dementia, to support decisions during the COVID‐19 pandemic and beyond. Methods Semi‐structured interviews were undertaken in 2020 with: (1) staff from two English national end‐of‐life and supportive care organizations; and (2) people living with dementia and family carers. Simultaneously, a rapid review of current evidence on making decisions with older people at the end of life was undertaken. Evidence from these inputs was combined to shape the decision‐aid through a series of workshops with key stakeholders, including our patient and public involvement group, which consisted of a person living with dementia and family carers; a group of clinical and academic experts and a group of policy and charity leads. Results The rapid review of existing evidence highlighted the need to consider both process and outcome elements of decision‐making and their effects on people living with dementia and their families. The qualitative interviews discussed a wide range of topics, including trust, agency and confusion in making decisions in the context of COVID‐19. The decision‐aid primarily focussed on care moves, legal matters, carer wellbeing and help‐seeking. Conclusions Combining different sources and forms of evidence was a robust and systematic process that proved efficient and valuable in creating a novel decision‐aid for family carers within the context of COVID‐19. The output from this process is an evidence‐based practical decision‐aid coproduced with people living with dementia, family carers, clinical and academic experts and leading national dementia and palliative care organizations. Patient or Public Contribution We worked with people living with dementia and family carers and other key stakeholders throughout this study, from study development and design to inclusion in stakeholder workshops and dissemination.

ObjectiveThe proposed scoping review aims to explore international literature on how older people from minority ethnic groups engage with and utilise palliative and end of life care, investigate the barriers and facilitators, and compare how this varies between ethnicities and health conditions.IntroductionMinority ethnic groups make up substantial parts of the populations of many countries around the world. Research has found that there are disparities in access to palliative care and end of life care among minority ethnic groups. Language barriers, cultural values, and socio-demographic factors have been cited as preventing access to quality palliative and end of life care. However, it is unclear how these barriers and inequalities differ across different minority ethnic groups in different countries, and across different health conditions within these groups.Inclusion criteriaThe population will be older people of different minority ethnic groups who are receiving palliative or end of life care, family caregivers, and health and social care professionals. The sources of information will include quantitative, qualitative and mixed methods research, and sources that focus on minority ethnic groups' interactions with palliative and end of life care.MethodsA scoping review guided by the Joanna Briggs Institute Manual for Evidence Synthesis. Searches of MEDLINE, Embase, PsycInfo, CINAHL, Scopus, Web of Science, Assia, and the Cochrane Library will be conducted. Citation tracking, reference list checking and grey literature searches will be undertaken. Data will be extracted, charted and summarised descriptively.ImplicationsThis review will highlight the health inequalities present in palliative and end of life care, the research gaps in understudied minority ethnic populations, locations where further study is required, and how barriers and facilitators differ across different ethnic groups and health conditions. The results of this review will be shared with stakeholders and will provide evidence-based recommendations for inclusive palliative and end of life care.

Abstract Background Family carers of people living with dementia often need support with making decisions about care. Many find end‐of‐life care decisions particularly difficult. The aim of this article is to present an evidence‐ and theoretical‐based process for developing a decision aid to support family carers of people with dementia towards the end‐of‐life. Methods Following a systematic process, we developed a decision aid using coproduction methods and matrices to synthesize data from a systematic review and qualitative interviews with people living with dementia and family carers. Data were presented to coproduction workshops of people living with dementia, family carers, practitioners and professionals. Development was guided by the Ottawa Decision Support Framework and a modified Interprofessional Shared Decision‐Making model. Results The decision aid covers four decision areas: (1) changes in care; (2) eating and drinking difficulties; (3) everyday well‐being; and (4) healthcare, tests and medication. We present an interactive decision aid, using a variety of approaches including written text, Frequently Asked Questions, top tips and illustrative quotes from people living with dementia and family carers. Conclusion This is the first decision aid that focusses on multiple decisions towards the end‐of‐life in dementia care. The process offers a template for others to develop decision aids or similar interventions, and how to include people living with dementia in coproduction. Patient or Public Contribution Family carers provided feedback on data collection, data analysis and the decision aid, and one is a coauthor. People living with dementia and family carers were integral to the coproduction workshops.

Abstract Background People living with dementia account for a large proportion of deaths due to COVID-19. Family carers are faced with making significant and emotive decisions during the pandemic, including decisions about end of life. We aimed to explore the challenges faced by family carers of people living with dementia during the first wave of the COVID-19 pandemic in England, as reported by charity telephone support line staff, who were able to objectively discuss a range of different experiences of many different carers who call the helpline. In particular, we focussed on key concerns and areas of decision making at the end of life. Methods We conducted a qualitative study using semi-structured interviews with eight telephone support line staff from two UK based charities who support carers of people living with dementia and those at the end of life. Interviews were conducted in the first wave of the pandemic in England in May–June 2020. Results An overarching theme of uncertainty and reactivity during a crisis was identified, and within this, five main themes were identified: concerns about care transitions, uncertainty in engaging support and help, pandemic-motivated care planning, maintaining the wellbeing of the person living with dementia, and trust, loss of agency and confusion. Conclusions Family carers may be reluctant to seek support because of fear of what may happen to their relative, which may include hospitalisation and becoming ill with COVID-19, care home placement, or not being able to be with a relative at the end of life. In some cases, a lack of trust has developed, and instead carers are seeking support from alternative services they trust such as nationally known charities.This study was used to inform the development of a decision aid to support family carers making decisions about care for their relative with dementia during the pandemic, who the lack the capacity to make their own decisions.

Summary: Background: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1β (IL-1β) blockade using canakinumab improves clinical outcome. Methods: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2 hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. Findings: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. Interpretation: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. Funding: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication.

Consumer reviews on platforms like Amazon are summarized into star ratings, used to weight search results, and consulted by consumers to guide purchase decisions. They are emblematic of the interactive digital environment that has purportedly transferred power from marketers to ‘regular people,’ and yet they represent the infiltration of promotional concerns into online information, as has occurred in search and social media content. Consumers’ ratings and reviews do promotional work for brands—not just for products but the platforms that host reviews—that money can’t always buy. Gains in power by consumers are quickly met with new strategies of control by companies who depend on reviews for reputational capital. Focusing on ecommerce giant Amazon, this article examines the complexities of online reviews, where individual efforts to provide product feedback and help others make choices become transformed into an information commodity and promotional vehicle. It acknowledges the ambiguous nature of reviews due to the rise of industries and business practices that influence or fake reviews as a promotional strategy. In response are yet other business practices and platform policies aiming to provide better information to consumers, protect the image of platforms that host reviews, and punish ‘bad actors’ in competitive markets. The complexity in the production, regulation, and manipulation of product ratings and reviews illustrates how the high stakes of attention in digital spaces create fertile ground for disinformation, which only emphasizes to users that they inhabit a ‘post-truth’ reality online.

BACKGROUND Neutralizing antibodies are considered a key correlate of protection by current SARS-CoV-2 vaccines. The manner in which human infections respond to therapeutic SARS-CoV-2 antibodies, including convalescent plasma therapy, remains to be fully elucidated.METHODS We conducted a proof-of-principle study of convalescent plasma therapy based on a phase I trial in 30 hospitalized COVID-19 patients with a median interval between onset of symptoms and first transfusion of 9 days (IQR, 7–11.8 days). Comprehensive longitudinal monitoring of the virological, serological, and disease status of recipients allowed deciphering of parameters on which plasma therapy efficacy depends.RESULTS In this trial, convalescent plasma therapy was safe as evidenced by the absence of transfusion-related adverse events and low mortality (3.3%). Treatment with highly neutralizing plasma was significantly associated with faster virus clearance, as demonstrated by Kaplan-Meier analysis (P = 0.034) and confirmed in a parametric survival model including viral load and comorbidity (adjusted hazard ratio, 3.0; 95% CI, 1.1–8.1; P = 0.026). The onset of endogenous neutralization affected viral clearance, but even after adjustment for their pretransfusion endogenous neutralization status, recipients benefitted from plasma therapy with high neutralizing antibodies (hazard ratio, 3.5; 95% CI, 1.1–11; P = 0.034).CONCLUSION Our data demonstrate a clear impact of exogenous antibody therapy on the rapid clearance of viremia before and after onset of the endogenous neutralizing response, and point beyond antibody-based interventions to critical laboratory parameters for improved evaluation of current and future SARS-CoV-2 therapies.TRIAL REGISTRATION ClinicalTrials.gov NCT04869072.FUNDING This study was funded via an Innovation Pool project by the University Hospital Zurich; the Swiss Red Cross Glückskette Corona Funding; Pandemiefonds of the UZH Foundation; and the Clinical Research Priority Program “Comprehensive Genomic Pathogen Detection” of the University of Zurich.

This study examines the international activist movement known as Sleeping Giants, a social-media “campaign to make bigotry and sexism less profitable” (Sleeping Giants, n.d.). The campaign originated in the US with an anonymous Twitter account that enlisted followers in encouraging brands to pull their online advertising from Breitbart News. The campaign achieved dramatic success and rapidly spread to regions outside the US, with other anonymously run and loosely allied chapters emerging in 15 different nations (as well as a regional chapter for the EU). Many of these were initially created to take on Breitbart advertisers in their home countries, but in a number of cases they subsequently turned their attention to disrupting financial support for other far-right news media in—or impacting—their home countries. Based on interviews with leaders of eight Sleeping Giants chapters, as well as the related UK-based Stop Funding Hate campaign, this study examines the Sleeping Giants campaign with respect to its continuity with media activism of previous eras, while also seeking to understand its potential as one of the first high-profile activist campaigns to grapple with the impacts of programmatic advertising on the news ecosystem. In particular, we consider how the campaign’s interventions speak to the larger debate around the normative relationship between advertising and the performance of the news ecosystem.

Summary: Staphylococcus aureus is the most common cause of skin and soft tissue infections, yet the bacterial genetic changes associated with adaptation to human skin are not well characterized. S. aureus strains isolated from patients with chronic skin colonization and intermittent infection were used to determine the staphylococcal genotypes or phenotypes associated with adaptation to human skin. We demonstrate that polymorphisms in metabolic genes, particularly those involved in the tricarboxylic acid cycle, the fumarate-succinate axis, and the generation of terminal electron transporters, are unexpectedly common. These skin-adapted strains activated glycolysis and hypoxia-inducible factor-1α, interleukin (IL)-1β, and IL-18 release from keratinocytes and promoted dermatopathology equivalent to a methicillin-resistant Staphylococcus aureus USA300 control in a murine model of infection. However, in contrast to USA300, a skin-adapted isolate failed to generate protection from a secondary infectious challenge. Within the context of human skin, there appears to be selection for S. aureus metabolic adaptive changes that promote glycolysis and maintain pathogenicity. : Bacteriology; Microbial Genetics; Microbiome Subject Areas: Bacteriology, Microbial Genetics, Microbiome

Introduction Despite community efforts to support and enable older and vulnerable people during the COVID-19 pandemic, many people with dementia and their family carers are still finding it difficult to adjust their daily living in light of the disruption that the pandemic has caused. There may be needs specific to black, Asian and minority ethnic (BAME) populations in these circumstances that remain thus far unexplored.Objective The aim of the study was to explore the effects of the COVID-19 pandemic on people living with dementia and their family carers of BAME backgrounds, in relation to their experiences of community dementia care and the impact on their daily lives.Design 15 participants (persons with dementia and carers) were recruited for semistructured qualitative interviews. Respondents were of South Asian and Afro-Caribbean backgrounds. We used thematic analysis to analyse our data from a constructivist perspective, which emphasises the importance of multiple perspectives, contexts and values.Results There were a number of ways that the COVID-19 pandemic has impacted BAME persons with dementia and carers with regard to their experiences of dementia community care and the impact on their everyday lives. In particular we identified eight key themes, with subthemes: fear and anxiety, food and eating (encompassing food shopping and eating patterns), isolation and identity, community and social relationships, adapting to COVID-19, social isolation and support structures, and medical interactions. Fear and anxiety formed an overarching theme that encompassed all others.Discussion This paper covers unique and underexplored topics in a COVID-19-vulnerable group. There is limited work with these groups in the UK and this is especially true in COVID-19. The results showed that such impacts were far-reaching and affected not only day-to-day concerns, but also care decisions with long-ranging consequences, and existential interests around fear, faith, death and identity.

ABSTRACT Skin is the most common site of Staphylococcus aureus infection. While most of these infections are self-limited, recurrent infections are common. Keratinocytes and recruited immune cells participate in skin defense against infection. We postulated that S. aureus is able to adapt to the milieu within human keratinocytes to avoid keratinocyte-mediated clearance. From a collection of S. aureus isolated from chronically infected patients with atopic dermatitis, we noted 22% had an agr mutant-like phenotype. Using several models of human skin infection, we demonstrate that toxin-deficient, agr mutants of methicillin-resistant S. aureus (MRSA) USA300 are able to persist within keratinocytes by stimulating autophagy and evading caspase-1 and inflammasome activation. MRSA infection induced keratinocyte autophagy, as evidenced by galectin-8 and LC3 accumulation. Autophagy promoted the degradation of inflammasome components and facilitated staphylococcal survival. The recovery of more than 58% agr or RNAIII mutants (P < 0.0001) of an inoculum of wild-type (WT) MRSA from within wortmannin-treated keratinocytes compared to control keratinocytes reflected the survival advantage for mutants no longer expressing agr-dependent toxins. Our results illustrate the dynamic interplay between S. aureus and keratinocytes that can result in the selection of mutants that have adapted specifically to evade keratinocyte-mediated clearance mechanisms. IMPORTANCE Human skin is a major site of staphylococcal infection, and keratinocytes actively participate in eradication of these pathogens. We demonstrate that methicillin-resistant Staphylococcus aureus (MRSA) is ingested by keratinocytes and activates caspase-1-mediated clearance through pyroptosis. Toxin-deficient MRSA mutants are selected within keratinocytes that fail to induce caspase-1 activity and keratinocyte-mediated clearance. These intracellular staphylococci induce autophagy that enhances their intracellular survival by diminishing inflammasome components. These findings suggest that S. aureus mutants, by exploiting autophagy, can persist within human keratinocytes.