Introducing multidisciplinary ward rounds in Malawi: a best practice implementation project.

INTRODUCTION: The Royal College of Physicians (RCP) and the Royal College of Nursing (RCN) in the United Kingdom advocate the use of structured multidisciplinary team (MDT) ward rounds since they can enable safe, effective, improved care and enhanced staff satisfaction. OBJECTIVES: This project sought to implement best practices for MDT ward rounds in a male medical ward in a hospital in Malawi. METHODS: The project was conducted in line with the JBI Evidence Implementation Framework. A baseline audit of MDT ward rounds was conducted with six staff members. Audit criteria consisted of ten best practices, as recommended by JBI, the RCP, and the RCN. Stakeholder meetings were held to review the baseline audit results and highlight areas of non-compliance. JBI's Getting Research into Practice (GRiP) tool was used to identify barriers to compliance with best practices, and a follow-up audit was conducted to determine changes in practice. RESULTS: The results only showed improvement for one criterion, which rose from 33% to 100% (n=6) where nurses attended the ward round. CONCLUSIONS: This study demonstrated some challenges in evidence implementation projects and how these can, in part, be overcome. While the results only demonstrated improvement for one criterion, this paper shows how audits can be used to promote best practice, which in this case resulted in nurses being more involved in ward rounds, improvements in MDT communication, enhanced nurse inclusion in decision-making and, consequently, patient care. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A233.

Sparsely PEGylated poly(beta-amino ester) polyplexes enhance antigen specific T-cell response of a bivalent SARS-CoV-2 DNA vaccine.

DNA technology has emerged as a promising route to accelerated manufacture of sequence agnostic vaccines. For activity, DNA vaccines must be protected and delivered to the correct antigen presenting cells. However, the physicochemical properties of the vector must be carefully tuned to enhance interaction with immune cells and generate sufficient immune response for disease protection. In this study, we have engineered a range of polymer-based nanocarriers based on the poly(beta-amino ester) (PBAE) polycation platform to investigate the role that surface poly(ethylene glycol) (PEG) density has on pDNA encapsulation, formulation properties and gene transfectability both in vitro and in vivo. We achieved this by synthesising a non-PEGylated and PEGylated PBAE and produced formulations containing these PBAEs, and mixed polyplexes to tune surface PEG density. All polymers and co-formulations produced small polyplex nanoparticles with almost complete encapsulation of the cargo in all cases. Despite high gene transfection in HEK293T cells, only the fully PEGylated and mixed formulations displayed significantly higher expression of the reporter gene than the negative control in dendritic cells. Further in vivo studies with a bivalent SARS-CoV-2 pDNA vaccine revealed that only the mixed formulation led to strong antigen specific T-cell responses, however this did not translate into the presence of serum antibodies indicating the need for further studies into improving immunisation with polymer delivery systems.

Lung transplant recipients' experiences of and attitudes towards self-management: a qualitative systematic review.

OBJECTIVE: The objective of this review was to identify lung transplant recipients' experiences of and attitudes towards self-management. INTRODUCTION: Lung transplantation is an established treatment to improve the survival of patients with end-stage lung diseases and has been performed on over 40,000 patients worldwide. The current focus of care for lung transplant recipients is on their long-term management. Patients need to adapt and adhere to complex self-management tasks to prevent complications and to enable them to keep the transplanted graft as long as possible. However, to date, no qualitative systematic review exists that identifies lung transplant recipients' experiences of and attitudes towards self-management. INCLUSION CRITERIA: This review included adults over 18 years of age who had received a lung transplant and were able to perform their self-management tasks independently. All studies that investigated lung transplant recipients' experiences of and attitudes towards self-management in any setting were included in this review. All types of studies that focused on qualitative data, including, but not limited to, phenomenology, grounded theory, ethnography, action research, and feminist research were considered for inclusion. Mixed methods studies were included only when qualitative data could be extracted separately, and if they reported results relating to the phenomena of interest. Studies published in English or German were considered for inclusion in this review. METHODS: The search strategy aimed to find published studies from 6 databases from the database inception to March 2022. Methodological quality of studies was independently assessed by 2 independent reviewers using the JBI checklist for qualitative research. A standardized data extraction tool from JBI was used by 2 reviewers for data collection. Meta-aggregation was undertaken to synthesize the data, and the final synthesis of the findings was reached through discussion. Results were graded according to ConQual. RESULTS: Ten studies with a sample size from 8 to 73 participants from North America and Central/Northern Europe were included in the review. The critical appraisal scores of the included studies varied from 3 to 9 out of 10. A total of 137 findings were extracted and aggregated to form 19 categories and the following 4 aggregated syntheses: i) Changes in routines, beliefs, and sense of responsibility are essential for better adaptation and self-management after lung transplantation; ii) Life after transplantation is characterized by both positive and negative feelings and experiences; iii) Better adjustment and self-management after a lung transplant require dealing with one's own feelings and beliefs; iv) After transplantation, engaging with relatives, friends, medical team and donors is essential to improve experiences and adapt to being a transplant recipient. Based on the ConQual scores, 2 synthesized findings were graded as moderate and 2 as low. CONCLUSIONS: Nuanced emotional, social, relational, and psychological adjustment is required of lung transplant recipients to be able to successfully self-manage. Loved ones and health professionals contribute significantly to this process, but psychosocial or peer support may further facilitate this transition. SUPPLEMENTAL DIGITAL CONTENT: A German-language version of the abstract of this review is available as Supplemental Digital Content [http://links.lww.com/SRX/A46].

Insufficient Sleep and Behavioral Health in the Military: A 5-Country Perspective.

PURPOSE OF REVIEW: The goal of this paper was to highlight the degree to which sleep, behavioral health, and leader involvement were interrelated using data from militaries in five English-speaking countries: Australia, Canada, New Zealand, the UK, and the United States. RECENT FINDINGS: Many service members reported sleeping fewer than the recommended 7 h/night: 34.9%, 67.2%, and 77.2% of respondents from New Zealand, Canada, and the United States, respectively. Countries reporting shorter sleep duration also reported fewer insomnia-related difficulties, likely reflecting higher sleep pressure from chronic sleep loss. Across all countries, sleep problems were positively correlated with behavioral health symptoms. Importantly, leader promotion of healthy sleep was positively correlated with more sleep and negatively correlated with sleep problems and behavioral health symptoms. Insufficient sleep in the military is ubiquitous, with serious implications for the behavioral health and functioning of service members. Leaders should attend to these risks and examine ways to promote healthy sleep in service members.

Student nurse retention. Lived experience of mature female students on a UK Bachelor of Nursing (Adult) programme: An interpretative phenomenological analysis.

AIMS: To explore the lived experiences of mature female students undertaking a Bachelor of Nursing (Adult) programme in the UK, to gain insight into the challenges and barriers faced by students and investigate the factors that support students who have considered leaving, to stay and continue with their studies. BACKGROUND: There is a global shortage of nurses and challenges exist in ensuring that enough nurses are available to provide care in the complex and rapidly changing care environments. Initiatives introduced to increase the number of Registered Nurses (RN), include increasing the number of students enrolled on pre-registration nursing programmes. However, the success of this intervention is contingent on the number of students who go on to complete their course. DESIGN: This qualitative study employed Interpretative Phenomenological Analysis (IPA), which provided a methodological framework and analytical approach to enable an exploration of participants' individual and shared lived experiences. METHODS: Eight female, mature students at the end of their second year of a Bachelor of Nursing (Adult) programme at a Higher Education Institution in South Wales participated in semi-structured, face-to-face interviews, which were analysed idiographically before group-level analysis was undertaken. FINDINGS: The analysis revealed three superordinate themes: 'Ambition to become a Registered Nurse'; 'Jugging Roles' and 'Particular Support Needs for a Particular Student'. CONCLUSION: Each student had a unique history, their past and present social and psychological experiences were multifaceted and complex. These differences resulted in varying degrees of resilience and motivations to continue their studies. These findings are important for ensuring that services develop and provide effective support to maximize retention and, ultimately, increase the number of students entering the RN workforce. PATIENT OF PUBLIC CONTRIBUTION: No patient or public contribution. IMPACT STATEMENT: This research expands on current literature regarding the needs of mature female students, a growing student nurse demographic. Every student had a dynamic set of circumstances and demonstrated that the identification of 'at-risk' students, purely based on demographics or information on a Curriculum Vitae, is problematic and potentially futile. This knowledge could be used to tailor University support systems and inform curriculum development and support systems for maximizing student retention. These findings are important for ensuring that services continue to develop and provide effective support to maximize retention and completion and, ultimately, increase the number of students entering the Nursing and Midwifery Council register.

Cancer vaccines: from an immunology perspective.

The concept of a therapeutic cancer vaccine to activate anti-tumour immunity pre-dates innovations in checkpoint blockade immunotherapies. However, vaccination strategies have yet to show the hoped-for successes in patients, and unanswered questions regarding the underlying immunological mechanisms behind cancer vaccines have hampered translation to clinical practice. Recent advances in our understanding of the potential of tumour mutational burden and neo-antigen-reactive T cells for response to immunotherapy have re-ignited enthusiasm for cancer vaccination strategies, coupled with the development of novel mRNA-based vaccines following successes in prevention of COVID-19. Here we summarise current developments in cancer vaccines and discuss how advances in our comprehension of the cellular interplay in immunotherapy-responsive tumours may inform better design of therapeutic cancer vaccines, with a focus on the role of dendritic cells as the orchestrators of anti-tumour immunity. The increasing number of clinical trials and research being funnelled into cancer vaccines has demonstrated the 'proof-of-principle', supporting the hypothesis that therapeutic vaccines have potential as an immuno-oncology agent. For efficacious and safe cancer vaccines to be developed, better understanding of the underpinning immunological mechanisms is paramount.

Crisis care for children and young people with mental health problems: national mapping, models of delivery, sustainability and experience (CAMH-Crisis2). A study protocol.

Background: One in six five 16-year-olds have a probable mental health difficulty. Of these, almost half of older teenagers and a quarter of 11-16-year-olds report having self-harmed or attempted suicide. Currently, there is little research into mental health crisis services for young people, with little understanding of what services exist, who uses them, or what works best. Question: 'How are mental health crisis responses for children and young people up to the age of 25 sustained, experienced and integrated within their local systems of services'? Objectives:     1.    To describe National Health Service (NHS), local authority, education and third sector approaches to the implementation and organisation of crisis care for children and young people across England and Wales.    2.   To identify eight contrasting case studies in which to evaluate how crisis services have developed and are currently organised, sustained, experienced and integrated within the context of their local systems of services.    3.   To compare and contrast these services in the context of the available international evidence, drawing out and disseminating clear implications for the design and delivery of future crisis responses for children and young people and their families. Methods: A sequential mixed methods approach, underpinned by normalisation process theory will be employed. A survey will create a detailed record of how crisis responses across England and Wales are organised, implemented and used. Subsequently, eight contrasting services in relation to geographic and socioeconomic setting, populations served, and service configuration will be identified as case studies. Interviews will be conducted with children, young people and parents/carers who have used the service, as well as commissioners, managers and practitioners. Operational policies and service usage data will also be examined. Analysis of how each service is provided, experienced, implemented and sustained will be conducted both inductively and deductively, reflecting normalisation process theory constructs.

BACKGROUND: There has been a sharp increase in children and young people experiencing extreme emotional distress and/or self-harm, which is also known as 'crisis'. Services for young people in crisis are a priority in the UK but little is currently known about what crisis services exist, who uses them, or what type of service works best. AIM AND OBJECTIVES: This project aims to explore the types of mental health crisis services currently available to children and young people up to the age of 25 in England and Wales, and to examine how they are organised, perceived and integrated within other local care systems. The objectives are to: 1. Find out what NHS, local authority, education and charity sector crisis services exist for children and young people across England and Wales, to describe the services and to create a database of them. 2. Identify eight contrasting services from the database and evaluate how these services are organised, perceived and integrated within local care systems. 3. Compare and contrast these services with the available international evidence, drawing out clear implications for the design and delivery of future crisis responses for children and young people and their families. METHODS: We will use a survey to create a database of crisis response services across England and Wales. From the database we will identify eight contrasting services and we will conduct interviews with children, young people and parents/carers who have used the service as well as managers and staff. We will look at how the services work and explore how they are used and by whom. We will compare and contrast each case study and consider findings of other research studies from around the world to draw clear, actionable, lessons for the future provision of high-quality crisis services for children and young people.

Metabolic adaption of mucosal macrophages: Is metabolism a driver of persistence across tissues?

Macrophages play essential roles in tissue homeostasis, defense, and repair. Their functions are highly tissue-specific, and when damage and inflammation stimulate repopulation by circulating monocytes, the incoming monocytes rapidly acquire the same, tissue-specific functions as the previous, resident macrophages. Several environmental factors are thought to guide the functional differentiation of recruited monocytes, including metabolic pressures imposed by the fuel sources available in each tissue. Here we discuss whether such a model of metabolic determinism can be applied to macrophage differentiation across barrier sites, from the lung to the skin. We suggest an alternative model, in which metabolic phenotype is a consequence of macrophage longevity rather than an early driver of tissue-specific adaption.

Impaired expression of metallothioneins contributes to allergen-induced inflammation in patients with atopic dermatitis.

Regulation of cutaneous immunity is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance versus inflammation in atopic dermatitis, we utilise a human in vivo allergen challenge study, exposing atopic dermatitis patients to house dust mite. Here we analyse transcriptional programmes at the population and single cell levels in parallel with immunophenotyping of cutaneous immunocytes revealed a distinct dichotomy in atopic dermatitis patient responsiveness to house dust mite challenge. Our study shows that reactivity to house dust mite was associated with high basal levels of TNF-expressing cutaneous Th17 T cells, and documents the presence of hub structures where Langerhans cells and T cells co-localised. Mechanistically, we identify expression of metallothioneins and transcriptional programmes encoding antioxidant defences across all skin cell types, that appear to protect against allergen-induced inflammation. Furthermore, single nucleotide polymorphisms in the MTIX gene are associated with patients who did not react to house dust mite, opening up possibilities for therapeutic interventions modulating metallothionein expression in atopic dermatitis.

Localized immune surveillance of primary melanoma in the skin deciphered through executable modeling.

While skin is a site of active immune surveillance, primary melanomas often escape detection. Here, we have developed an in silico model to determine the local cross-talk between melanomas and Langerhans cells (LCs), the primary antigen-presenting cells at the site of melanoma development. The model predicts that melanomas fail to activate LC migration to lymph nodes until tumors reach a critical size, which is determined by a positive TNF-α feedback loop within melanomas, in line with our observations of murine tumors. In silico drug screening, supported by subsequent experimental testing, shows that treatment of primary tumors with MAPK pathway inhibitors may further prevent LC migration. In addition, our in silico model predicts treatment combinations that bypass LC dysfunction. In conclusion, our combined approach of in silico and in vivo studies suggests a molecular mechanism that explains how early melanomas develop under the radar of immune surveillance by LC.

Which interventions improve HPV vaccination uptake and intention in children, adolescents and young adults? An umbrella review.

BACKGROUND: Human papillomavirus (HPV) vaccination offers protection against the virus responsible for cervical, oropharyngeal, anal, vulval and penile cancers. However, there is considerable variation across, and even within, countries as to how HPV vaccination is offered and accepted. This review aimed to identify what interventions exist to promote uptake and how effective they are. METHODS: We conducted an umbrella review using the JBI (Joanna Briggs Institute) methodology to evaluate routine or catch-up interventions to increase HPV vaccination uptake and/or intention for children aged 9 years and older, adolescents and young adults up to 26. Comprehensive searches for English language quantitative systematic reviews, published between January 2011 and July 2021, were conducted across five databases. After reviewing titles and abstract, relevant papers were independently assessed in detail. MAIN RESULTS: From 1046 records identified, 10 articles were included in the review. They reported on 95 randomised controlled trials, 28 quasi-experimental studies, 14 cohort studies, 6 non-randomised pretest/post-test studies with control groups, 5 single-group pretest/post-test studies, 1 single-group post-test study and 1 randomised longitudinal study. Some interventions promoted change at the individual, community or organisational level, while others used a multicomponent approach. Face-to-face presentations, printed information and supplementing both strategies with additional components appear effective at increasing vaccination intention, while reminders and multicomponent strategies, especially ones that include some intervention aimed at provider level, appear effective at increasing vaccination uptake. Interventions that did not lead to an improvement in HPV vaccination intention or uptake varied in design and impacts were inconsistent across children/adolescents, young adults or parents. CONCLUSION: The evidence suggests that there is no single solution to increasing vaccination uptake and that different approaches may be better suited to certain populations. However, generalisations are limited by poor reporting and a paucity of studies beyond the USA. Further high-quality studies, therefore, are needed to understand how best to increase HPV vaccination uptake in different target populations.

Enhancing the clinical supervision experience of staff members working within primary and community care: a best practice implementation project.

OBJECTIVES: The project aimed to assess compliance with evidence-based criteria regarding the use of clinical supervision amongst district nurses and to improve knowledge and engagement in clinical supervision activities within the workplace. INTRODUCTION: It is important to provide clinical support to all healthcare workers that provide opportunities to develop and be listened to in a supervised environment. Clinical supervision is seen as a key element to provide this support. It provides a professional working relationship between two or more members of staff where the reflection of practice and personal emotion can be discussed, which is outlined in many policies and guidelines. METHODS: A baseline audit was carried out using the JBI Practical Application of Clinical Evidence System program involving 16 participants in one district nursing team in South Wales. The first step involved the development of the project and generating the evidence. Following this, a baseline audit was conducted, and educational training on clinical supervision was undertaken followed by clinical supervision sessions. A postimplementation re-audit was conducted following implementation. RESULTS: A total of 16 participants enrolled on the project. Receiving basic training and participating in clinical supervision was much higher than the baseline audit with both increasing to 100% compliance. Furthermore, 94% of participants were aware of clinical supervision activities and 88% knew of existing records on clinical supervision. The project results show a large increase in compliance with all of the criteria. CONCLUSION: Overall the implementation project achieved an improvement in evidence-based practice regarding clinical supervision in primary care.

Loss of T cell tolerance in the skin following immunopathology is linked to failed restoration of the dermal niche by recruited macrophages.

T cell pathology in the skin leads to monocyte influx, but we have little understanding of the fate of recruited cells within the diseased niche, or the long-term impact on cutaneous immune homeostasis. By combining a murine model of acute graft-versus-host disease (aGVHD) with analysis of patient samples, we demonstrate that pathology initiates dermis-specific macrophage differentiation and show that aGVHD-primed macrophages continue to dominate the dermal compartment at the relative expense of quiescent MHCIIint cells. Exposure of the altered dermal niche to topical haptens after disease resolution results in hyper-activation of regulatory T cells (Treg), but local breakdown in tolerance. Disease-imprinted macrophages express increased IL-1ß and are predicted to elicit altered TNF superfamily interactions with cutaneous Treg, and we demonstrate the direct loss of T cell regulation within the resolved skin. Thus, T cell pathology leaves an immunological scar in the skin marked by failure to re-set immune homeostasis.

Impact of primary and recurrent genital herpes on the quality of life of young people and adults: a mixed methods systematic review.

OBJECTIVE: This review sought to identify the experiences of persons living with genital herpes and what interventions improve the health-related quality of life of young people and adults with primary or recurrent genital herpes. INTRODUCTION: Genital herpes is commonly associated with psychosocial challenges. However, a growing body of evidence suggests that its impact can be ameliorated through pharmacological and psychosocial interventions. INCLUSION CRITERIA: This review considered English- and German-language studies of community-dwelling males and females, of any ethnicity and geographical location, aged 15 years and older, who had primary or recurrent genital herpes. The quantitative component of the review included studies that reported on the virus' impact on patients' health-related quality of life and/or the efficacy of interventions in improving their health-related quality of life. Studies compared antiviral suppression therapies and psychological interventions with usual care or placebo, or against one another. The qualitative component of the review included studies that investigated the perceptions and experiences of young people and adults with genital herpes. METHODS: Eleven databases were searched from January 1980 to March 2020. The JBI approach to mixed methods systematic reviews was followed at each stage of the review, and a convergent segregated approach to synthesis and integration was adopted. RESULTS: A total of 31 publications covering 30 studies were deemed suitable for inclusion. Studies encompassed quantitative (n = 27, across 28 publications), qualitative (n = 1), and mixed methods (n = 2) designs. Critical appraisal scores were variable, particularly among the randomized controlled trials and the analytical cross-sectional studies. All studies were included regardless of methodological quality. The quantitative components identified that depression, illness concern, stress, anxiety, isolation, stigma, and a lowering of self-esteem, self-concept, self-confidence, and health-related quality of life may be experienced by both those newly diagnosed with genital herpes and those with recurrences. It was also identified that genital herpes can have an adverse effect on work or school, sexual relationships, and relationships with friends and family. Depression was found to significantly decrease after self-hypnosis and certain psychosocial interventions. Anxiety significantly decreased following pharmacological treatment, psychosocial interventions, and hypnosis. Psychosocial interventions significantly improved mood, and a self-help module with counseling significantly improved participants' satisfaction with intimate relationships and their self-esteem. Pharmacological treatment significantly improved health-related quality of life; however, there were no significant differences between different active treatment regimens. The qualitative component of the review led to the identification of two synthesized findings: "Disclosure of a diagnosis of genital herpes poses a dilemma for people who have the virus" and "A diagnosis of genital herpes has a significant emotional impact for the individual."Integration of quantitative and qualitative evidence revealed a consensus that a diagnosis of genital herpes has a significant emotional impact for individuals and that disclosure is stressful, affects relationships, and affects health-related quality of life; however, there is a lack of consensus regarding efficacy of different interventions. CONCLUSIONS: Genital herpes can lead to extreme emotional, social, relational, and sexual distress, but there is insufficient knowledge concerning which interventions best improve health-related quality of life. More high-quality research is required.

Executable network of SARS-CoV-2-host interaction predicts drug combination treatments.

The COVID-19 pandemic has pushed healthcare systems globally to a breaking point. The urgent need for effective and affordable COVID-19 treatments calls for repurposing combinations of approved drugs. The challenge is to identify which combinations are likely to be most effective and at what stages of the disease. Here, we present the first disease-stage executable signalling network model of SARS-CoV-2-host interactions used to predict effective repurposed drug combinations for treating early- and late stage severe disease. Using our executable model, we performed in silico screening of 9870 pairs of 140 potential targets and have identified nine new drug combinations. Camostat and Apilimod were predicted to be the most promising combination in effectively supressing viral replication in the early stages of severe disease and were validated experimentally in human Caco-2 cells. Our study further demonstrates the power of executable mechanistic modelling to enable rapid pre-clinical evaluation of combination therapies tailored to disease progression. It also presents a novel resource and expandable model system that can respond to further needs in the pandemic.

Pathways to mental health care in active military populations across the Five-Eyes nations: An integrated perspective.

Military service is associated with increased risk of mental health problems. Previous reviews have pointed to under-utilization of mental health services in military populations. Building on the most recent systematic review, our narrative, critical review takes a complementary approach and considers research across the Five-Eyes nations from the past six years to update and broaden the discussion on pathways to mental healthcare in military populations. We find that at a broad population level, there is improvement in several indicators of mental health care access, with greater gains in initial engagement, time to first treatment contact, and subjective satisfaction with care, and smaller gains in objective indicators of adequacy of care. Among individual-level barriers to care-seeking, there is progress in improving recognition of need for care and reducing stigma concerns. Among organizational-level barriers, there are advances in availability of services and cultural acceptance of care-seeking. Other barriers, such as concerns around confidentiality, career impact, and deployability persist, however, and may account for some remaining unmet need. To address these barriers, new initiatives that are more evidence-based, theoretically-driven, and culturally-sensitive, are therefore needed, and must be rigorously evaluated to ensure they bring about additional improvements in pathways to care.