Epidemiological features of depression and anxiety among homeless adults with healthcare access problems in London, UK: descriptive cross-sectional analysis.

BACKGROUND: In England in 2021, an estimated 274 000 people were homeless on a given night. It has long been recognised that physical and mental health of people who are homeless is poorer than for people who are housed. There are few peer-reviewed studies to inform health and social care for depression or anxiety among homeless adults in this setting. AIMS: To measure the symptoms of depression and anxiety among adults who are homeless and who have difficulty accessing healthcare, and to describe distribution of symptoms across sociodemographic, social vulnerability and health-related characteristics. METHOD: We completed structured questionnaires with 311 adults who were homeless and who had difficulty accessing healthcare in London, UK, between August and December 2021. We measured anxiety and depression symptoms using the 4-item Patient Health Questionnaire (PHQ-4) score. We compared median PHQ-4 scores across strata of the sociodemographic, social vulnerability and health-related characteristics, and tested for associations using the Kruskal-Wallis test. RESULTS: The median PHQ-4 score was 8 out of 12, and 40.2% had scores suggesting high clinical need. Although PHQ-4 scores were consistently high across a range of socioeconomic, social vulnerability and health-related characteristics, they were positively associated with: young age; food insecurity; recent and historic abuse; joint, bone or muscle problems; and frequency of marijuana use. The most common (60%) barrier to accessing healthcare related to transportation. CONCLUSIONS: Adults who are homeless and have difficulty accessing healthcare have high levels of depression and anxiety symptoms. Our findings support consideration of population-level, multisectoral intervention.

A deep dive into selected work sectors during the COVID-19 pandemic and the "living with COVID" phase: understanding similarities and differences in practice, perceptions, and preparedness.

OBJECTIVES: When it comes to controlling workplace transmission of SARS-CoV-2, the virus that causes COVID-19, different workplaces and industrial sectors face different challenges, both in terms of likely transmission routes and which control measures can be practically, economically, and effectively implemented. This article considers a large body of research in the United Kingdom across different work sectors and time points during the COVID-19 pandemic to better understand mitigation measures, challenges to mitigating the risk of SARS-COV-2 transmission, knowledge gaps, and barriers and enablers to control viral transmission. METHODS: Data is drawn from 2 phases of research. Phase 1 gathered data from an interactive workshop (April 2022) where PROTECT researchers working across 8 work sectors shared knowledge and expertise from research conducted between 2020 and 2022. Phase 2 revisited 6 of these sectors to explore participants' views on the "living with COVID" phase of the pandemic (February-October 2022) through qualitative interviews. RESULTS: Our findings emphasise the importance of considering the characteristics of each work sector (and their sub-sectors), relative to the physical workplace and workforce, the ways organisations operate, and how they interact with the public. Study findings show that participant's views and organisational practices changed quickly and significantly over the course of the pandemic. Most participants initially perceived that the majority of risk mitigations would remain in place for the foreseeable future. However, following the change in Government Guidance towards "living with COVID", most mitigation measures were quickly removed and it had become necessary for sectors/organisations to restore normal operations, thereby treating the COVID-19 virus like any other illness, while remaining prepared for future health emergencies that may arise. CONCLUSION: We suggest that national policy makers and organisational leaders remain mindful of the lessons learned and knowledge gained at all levels (national, regional, local, organisational, and individual) during the COVID-19 pandemic. We make recommendations in support of recovery as sectors/organisations continue "living with COVID" and other respiratory diseases; balanced with longer term planning for the next public health crisis.

Qualitative longitudinal research on the experience of implementing Covid-19 prevention in English schools.

Implementation studies rarely examine how health interventions are delivered in emergencies. Informed by May's general theory of implementation (GTI), we undertook qualitative longitudinal research to investigate how schools in England implemented Covid-19-prevention measures and how this evolved over the 2020-2021 school year in a rapidly changing epidemiological and policy context. We conducted 74 semi-structured interviews over two time-points with headteachers, teachers, parents and students across eight primary and secondary schools. School leaders rapidly made sense of government guidance despite many challenges. They developed and disseminated prevention plans to staff, parents and students. As defined by GTI, 'cognitive participation' and 'collective action' to enact handwashing, one-way systems within schools and enhanced cleaning were sustained over time. However, measures such as physical distancing and placing students in separated groups were perceived to conflict with schools' mission to promote student education and wellbeing. Commitment to implement these was initially high during the emergency phase but later fluctuated dependant on perceived risk and local disease epidemiology. They were not considered sustainable in the long term. Adherence to some measures, such as wearing face-coverings, initially considered unworkable, improved as they were routinised. Implementing home-based asymptomatic testing was considered feasible. Formal and informal processes of 'reflexive monitoring' by staff informed improvements in intervention workability and implementation. Leaders also developed skills and confidence, deciding on locally appropriate actions, some of which deviated from official guidance. However, over time, accumulating staff burnout and absence eroded school capacity to collectively enact implementation. Qualitative longitudinal research allowed us to understand how implementation in an emergency involved the above emergent processes. GTI was useful in understanding school implementation processes in a pandemic context but may need adaptation to take into account the changing and sometimes contradictory objectives, time-varying factors and feedback loops that can characterise implementation of health interventions in emergencies.

Preclinical evaluation of FLT190, a liver-directed AAV gene therapy for Fabry disease.

Fabry disease is an X-linked lysosomal storage disorder caused by loss of alpha-galactosidase A (α-Gal A) activity and is characterized by progressive accumulation of glycosphingolipids in multiple cells and tissues. FLT190, an investigational gene therapy, is currently being evaluated in a Phase 1/2 clinical trial in patients with Fabry disease (NCT04040049). FLT190 consists of a potent, synthetic capsid (AAVS3) containing an expression cassette with a codon-optimized human GLA cDNA under the control of a liver-specific promoter FRE1 (AAV2/S3-FRE1-GLAco). For mouse studies FLT190 genome was pseudotyped with AAV8 for efficient transduction. Preclinical studies in a murine model of Fabry disease (Gla-deficient mice), and non-human primates (NHPs) showed dose-dependent increases in plasma α-Gal A with steady-state observed 2 weeks following a single intravenous dose. In Fabry mice, AAV8-FLT190 treatment resulted in clearance of globotriaosylceramide (Gb3) and globotriaosylsphingosine (lyso-Gb3) in plasma, urine, kidney, and heart; electron microscopy analyses confirmed reductions in storage inclusion bodies in kidney and heart. In NHPs, α-Gal A expression was consistent with the levels of hGLA mRNA in liver, and no FLT190-related toxicities or adverse events were observed. Taken together, these studies demonstrate preclinical proof-of-concept of liver-directed gene therapy with FLT190 for the treatment of Fabry disease.

Transmission and Control of SARS-CoV-2 in the Food Production Sector: A Rapid Narrative Review of the Literature.

This review aimed to provide an overview of the literature assessing the extent of COVID-19 transmission in the food processing sector along with the risk factors associated with COVID-19 infection/mortality rates in this setting, and the preventive measures used to reduce transmission. An electronic search was conducted using scientific databases, including Web of Science, OVID, PubMed and MedRxiv. The search strategy identified 26 papers that met the inclusion criteria. Six of these studies were based in the UK and the country with the most papers was the USA, with a total of nine papers. Findings showed some evidence of a high transmission level of SARS-CoV-2 within some areas of the food production sector. Risk factors associated with the spread included ethnicity, poor ventilation, lack of social distancing and lack of sick pay. The preventative measures included/recommended were social distancing, testing, adequate ventilation, cleaning regimes and access to PPE. Additional research focusing on the food production sector could show the potential variations in transmission and risk between each sub-sector. Future research focusing on the application of various preventative measures and their efficacy by sub-sector would be beneficial, while further qualitative research could help provide in-depth information regarding knowledge gaps.

'Progression capitals': How homeless health peer advocacy impacts peer advocates.

This article presents analysis from a qualitative evaluation of a homeless health peer advocacy (HHPA) service in London, United Kingdom. Whilst evidence is growing for the impact of peer programming on clients, understanding of the impact on peers themselves is limited in the context of homelessness. Research here is vital for supporting sustainable and effective programmes. Analysis of interview data with 14 current and former peer advocates, 2 members of staff and 3 external stakeholders suggests peer advocacy and its organizational setting can generate social, human, cultural and physical resources to help peer advocates fulfil their own life goals. We explore these with reference to 'recovery capital', reframed as 'progression capitals' to reflect its relevance for pursuits unrelated to clinical understandings of recovery. Progression capitals can be defined as resources to pursue individually determined goals relating to self-fulfilment. We find engagement with, and benefits from, a peer advocacy service is most feasible among individuals already possessing some 'progression capital'. We discuss the value of progression capitals for peers alongside the implications of the role being unsalaried within a neoliberal political economy, and comment on the value that the progression capitals framework offers for the development and assessment of peer interventions more broadly.

Why were COVID-19 infections lower than expected amongst people who are homeless in London, UK in 2020? Exploring community perspectives and the multiple pathways of health inequalities in pandemics.

High rates of COVID-19 infections and deaths amongst people who are homeless in London, UK were feared. Rates however stayed much lower than expected throughout 2020; an experience that compares to other settings globally. This study sought a community level perspective to explore this rate of infections, and through this explore relationships between COVID-19 and existing health inequalities. Analyses are reported from ongoing qualitative studies on COVID-19 and homeless health service evaluation in London, UK. Repeated in-depth telephone interviews were implemented with people experiencing homelessness in London (n=17; 32 interviews in total) as well as street outreach workers, nurses and hostel staff (n=10) from September 2020 to early 2021. Thematic analysis generated three themes to explore peoples' experiences of, and perspectives on, low infections: people experiencing homelessness following, creating and breaking social distancing and hygiene measures; social distancing in the form of social exclusion as a long-running feature of life; and a narrative of 'street immunity' resulting from harsh living conditions. Further study is needed to understand how these factors combine to prevent COVID-19 and how they relate to different experiences of homelessness. This community perspective can ensure that emerging narratives of COVID-19 prevention success don't ignore longer running causes of homelessness and reinforce stigmatising notions of people who are homeless as lacking agency. Our findings aid theorisation of how health inequalities shape pandemic progression: severe exclusion may substantially delay epidemics in some communities, although with considerable other non-COVID-19 impacts.

Peer advocacy and access to healthcare for people who are homeless in London, UK: a mixed method impact, economic and process evaluation protocol.

INTRODUCTION: People who are homeless experience higher morbidity and mortality than the general population. These outcomes are exacerbated by inequitable access to healthcare. Emerging evidence suggests a role for peer advocates-that is, trained volunteers with lived experience-to support people who are homeless to access healthcare. METHODS AND ANALYSIS: We plan to conduct a mixed methods evaluation to assess the effects (qualitative, cohort and economic studies); processes and contexts (qualitative study); fidelity; and acceptability and reach (process study) of Peer Advocacy on people who are homeless and on peers themselves in London, UK. People with lived experience of homelessness are partners in the design, execution, analysis and dissemination of the evaluation. ETHICS AND DISSEMINATION: Ethics approval for all study designs has been granted by the National Health Service London-Dulwich Research Ethics Committee (UK) and the London School of Hygiene and Tropical Medicine's Ethics Committee (UK). We plan to disseminate study progress and outputs via a website, conference presentations, community meetings and peer-reviewed journal articles.