Mucosal T-cell responses to chronic viral infections: Implications for vaccine design.

Mucosal surfaces that line the respiratory, gastrointestinal and genitourinary tracts are the major interfaces between the immune system and the environment. Their unique immunological landscape is characterized by the necessity of balancing tolerance to commensal microorganisms and other innocuous exposures against protection from pathogenic threats such as viruses. Numerous pathogenic viruses, including herpesviruses and retroviruses, exploit this environment to establish chronic infection. Effector and regulatory T-cell populations, including effector and resident memory T cells, play instrumental roles in mediating the transition from acute to chronic infection, where a degree of viral replication is tolerated to minimize immunopathology. Persistent antigen exposure during chronic viral infection leads to the evolution and divergence of these responses. In this review, we discuss advances in the understanding of mucosal T-cell immunity during chronic viral infections and how features of T-cell responses develop in different chronic viral infections of the mucosa. We consider how insights into T-cell immunity at mucosal surfaces could inform vaccine strategies: not only to protect hosts from chronic viral infections but also to exploit viruses that can persist within mucosal surfaces as vaccine vectors.

Psychosocial Health Among Young Adults With Kidney Failure: A Longitudinal Follow-up of the SPEAK (Surveying Patients Experiencing Young Adult Kidney Failure) Study.

Rationale & Objective: There have been no longitudinal studies examining the evolution of psychosocial health of young adults with kidney failure as they age. We aimed to address this in the Surveying Patients Experiencing Young Adult Kidney Failure-2 (SPEAK-2) study. Study Design: 5-year follow-up longitudinal survey of the original SPEAK cohort. Setting & Participants: 16- to 30-year-olds in the UK receiving kidney replacement therapy (KRT) between 2015 and 2017 who participated in the SPEAK study. Exposure: Kidney failure and KRT modality. Outcomes: Psychosocial health and lifestyle behaviors. Analytical Approach: Within-cohort changes in psychosocial health were analyzed using the paired t test, Wilcoxon signed-rank test and McNemar's test. We compared responses to the age-matched population and examined the impact of changes in KRT modality on psychological health using linear regression for continuous outcome variables as well as logistic, ordered logistic and multinomial logistic regression for binary, ordered categorical and unordered categorical variables, respectively. Results: We obtained 158 survey responses; 129 had previously responded to SPEAK. Of these, 90% had a kidney transplant. Compared to the general population, respondents were less likely to be married or have children and were more likely to be living with their parents. Respondents had nearly 15 times greater odds of being unable to work due to health (odds ratio [OR] = 14.41; 95% confidence interval [CI], 8.0-26.01; P < 0.001). Respondents had poorer quality of life and mental wellbeing and were more likely to report psychological problems (OR = 5.37; 95% CI, 3.45-8.35; P < 0.001). A negative association between remaining on or moving to dialysis and psychosocial health was observed, although this was attenuated when controlling for the psychosocial state in SPEAK. Limitations: Low response rate resulting in imprecise and potentially biased estimates and impact of COVID-19 pandemic while survey was active on psychosocial health. Conclusions: Young adults with kidney failure have persistent poorer psychosocial health compared to their healthy peers as they age. Our findings also suggest a potential causal relationship between KRT modality and psychosocial health.

The psychosocial impact of kidney failure in young adults is implicated in the observed higher risk of transplant loss and death. The Surveying Patients Experiencing Young Adult Kidney Failure (SPEAK) study investigated the psychosocial health of young adults (16-30 years) in the UK receiving kidney replacement therapy and found they had poorer outcomes than the age-matched general population. In this 5-year follow-up study, we observed that as this group matured, they lagged behind their peers in terms of both lifecourse and psychological outcomes. Dialysis recipients had poorer psychosocial health compared to transplant recipients. This emphasizes the lasting impact of kidney failure on young adults' psychosocial health, particularly for those receiving dialysis, highlighting the need for better mental health support and treatment.

The experiences of UK-Chinese individuals during the COVID-19 pandemic: A qualitative interview study.

Infectious disease outbreaks have historically been associated with stigmatisation towards minority groups, specifically those associated with the geographical region that the disease was first identified. We aimed to investigate how the emerging COVID-19 pandemic was experienced by UK-resident individuals of Chinese ethnicity: how their perceived cultural and ethnic identity influenced their experiences, and how early insights into the pandemic in China influenced attitudes and behaviours. We undertook in-depth semi-structured interviews with individuals who self-identified as UK-Chinese. Participants were recruited from three cities in the UK. Interviews were undertaken over the telephone between 9th April 2020 and 16th July 2020. Interviews were digitally recorded and transcribed verbatim. Transcripts were coded using NVivo software and analysed using inductive thematic analysis. Sixteen individuals were interviewed. Three main themes were identified: (1) Attribution of stigma, (2) Pandemic legacies, and (3) Individual versus societal responses. These reflected six sub-themes: (1) Stigmatisation through (mis)identity, (2) Markers of pandemic awareness, (3) Legacies of previous pandemics, (4) Ascription of blame, (5) Extent of freedom, and (6) Implicit faith in government. Experiences of xenophobia included accounts of physical violence. UK-Chinese individuals experienced and perceived widespread xenophobia, in the context of media representations that ascribed blame and exacerbated stigmatisation. Prior experience of respiratory epidemics, and insight into the governmental and societal response in China, contributed to the early adoption of face masks. This in turn marked UK-Chinese individuals as targets for abuse. Awareness is needed to safeguard stigmatized groups from social and economic harm in future infectious disease pandemics.

Expectations of a new opt-out system of consent for deceased organ donation in England: A qualitative interview study.

INTRODUCTION: In 2020 England moved to an opt-out deceased donation law. We aimed to investigate the views of a mixed stakeholder group comprising people with kidney disease, family members and healthcare practitioners towards the change in legislation. We investigated the expected impacts of the new legislation on deceased-donor and living-donor transplantation, and views on media campaigns regarding the law change. METHODS: We undertook in-depth qualitative interviews with people with kidney disease (n = 13), their family members (n = 4) and healthcare practitioners (n = 15). Purposive sampling was used to ensure diversity for patients and healthcare practitioners. Family members were recruited through snowball sampling and posters. Interviews were audio-recorded and transcribed verbatim. Transcripts were analysed using thematic analysis. RESULTS: Three themes with six subthemes were identified: (i) Expectations of impact (Hopeful patients; Cautious healthcare professionals), (ii) Living-donor transplantation (Divergent views; Unchanged clinical recommendations), (iii) Media campaigns (Single message; Highlighting recipient benefits). Patients expected the law change would result in more deceased-donor transplant opportunities. CONCLUSIONS: Clinicians should ensure patients and families are aware of the current evidence regarding the impact of opt-out consent: expectations of an increased likelihood of receiving a deceased-donor transplant are not currently supported by the evidence. This may help to prevent a decline in living-donor transplantation seen in other countries with similar legislation. Media campaigns should include a focus on the impact of organ receipt. PATIENT OR PUBLIC CONTRIBUTION: Two patient representatives from the Kidney Disease Health Integration Team, Primrose Granville and Soumeya Bouacida, contributed to the content and design of the study documents.

Development of an intervention to improve access to living-donor kidney transplantation (the ASK study).

A living-donor kidney transplant (LDKT) is one of the best treatments for kidney failure. The UK's LDKT activity falls behind that of many other countries, and there is evidence of socioeconomic inequity in access. We aimed to develop a UK-specific multicomponent intervention to support eligible individuals to access a LDKT. The intervention was designed to support those who are socioeconomically-deprived and currently disadvantaged, by targeting mediators of inequity identified in earlier work. We identified three existing interventions in the literature which target these mediators: a) the Norway model (healthcare practitioners contact patients' family with information about kidney donation), b) a home education model, and c) a Transplant candidate advocate model. We undertook intervention development using the Person-Based Approach (PBA). We performed in-depth qualitative interviews with people with advanced kidney disease (n = 13), their family members (n = 4), and renal and transplant healthcare practitioners (n = 15), analysed using thematic analysis. We investigated participant views on each proposed intervention component. We drafted intervention resources and revised these in light of comments from qualitative 'think-aloud' interviews. Four general themes were identified: i) Perceived cultural and societal norms; ii) Influence of family on decision-making; iii) Resource limitation, and iv) Evidence of effectiveness. For each intervention discussed, we identified three themes: for the Norway model: i) Overcoming communication barriers and assumptions; ii) Request from an official third party, and iii) Risk of coercion; for the home education model: i) Intragroup dynamics; ii) Avoidance of hospital, and iii) Burdens on participants; and for the transplant candidate advocates model: i) Vested interest of advocates; ii) Time commitment, and iii) Risk of misinformation. We used these results to develop a multicomponent intervention which comprises components from existing interventions that have been adapted to increase acceptability and engagement in a UK population. This will be evaluated in a future randomised controlled trial.

The management and outcomes of Staphylococcus aureus bacteraemia at a South African referral hospital: A prospective observational study.

OBJECTIVES: Data on the management and outcomes of Staphylococcus aureus bacteraemia (SAB) in resource-limited settings are limited. The aim of this study was to describe a cohort of South African patients with SAB, and explore the factors associated with complicated infection and death. METHODS: This was a prospective observational study of patients over the age of 13 years admitted to a South African referral hospital with SAB. RESULTS: One hundred SAB infection episodes occurring in 98 patients were included. SAB was healthcare-associated in 68.4%; 24.0% of all cases were caused by methicillin-resistant S. aureus (MRSA). Ninety-day mortality was 47.0%, with 83.3% of deaths attributable to SAB. There was a trend towards increased 90-day mortality with MRSA infection (odds ratio (OR) 1.28, 95% confidence interval (CI) 1.0-15.1) and the presence of comorbidities (OR 4.1, 95% CI 1.0-21.6). The risk of complicated infection was higher with non-optimal definitive antibiotic therapy (OR 8.5, 95% CI 1.8-52.4), female sex (OR 3.8, 95% CI 1.1-16.3), and community-acquired infection (OR 7.4, 95% CI 2.0-33.1). Definitive antibiotic therapy was non-optimal in 22.6% of all cases. CONCLUSIONS: SAB-related mortality was high. A large proportion of cases may be preventable, and there is a need for improved antibiotic management.

Speeding up laboratory test reporting in Medical Emergency and Cardiac Arrest calls: a quality improvement project.

Many hospitals deploy Medical Emergency (MET) and Cardiac Arrest teams to improve the management and treatment of patients who become critically ill. In many cases, blood results are key in allowing the clinicians involved in these teams to make definitive management decisions for these patients. Following anecdotal reports that these results were often delayed, we assessed the process of blood tests being reported in emergency calls, identified the key factors causing delays and sought to make improvements. The initial intervention involved implementing a new blood form that specified the nature of the call, the tests required and a contact number for laboratory staff to contact the clinical team with results. We also developed a streamlined process within the laboratory for these samples to be fast-tracked. Successive improvement cycles sought to increase awareness of the project, improve accessibility to the new forms and embed spontaneous practices that contributed to improvement. Results demonstrated an overall reduction in the time taken for blood samples in emergencies to be reported from 130 minutes to 97 minutes. This project demonstrates that using a specific blood request form for emergency calls, and tying this to a specified laboratory process, improves the time taken for these tests to be reported. In addition, the project provides some insight into challenges faced when implementing change in new departments.