Community efforts to promote vaccine uptake in a rural setting: a qualitative interview study.

Vaccine hesitancy has been identified as one of the top 10 threats to global health. The causes of low vaccine uptake are many and vary at micro and macro levels. However, rural and remote coastal areas in the UK experience unique vaccine inequalities due to high levels of deprivation and their unique and complex access-related problems. This study aimed to explore community efforts to promote vaccine uptake during the COVID-19 pandemic and understand how the COVID-19 vaccination campaign was experienced by the public. We conducted an exploratory descriptive qualitative study using semi-structured interviews with decision-makers, health professionals and community members in Lincolnshire, a predominantly rural county with a long coastline, a large population of white minority ethnicities, and those living in caravan and temporary housing. Data were analysed using conventional content analysis. Overcoming the various access barriers to vaccination uptake involved working with local media stations, local communities and local community groups, translation of information, bringing vaccines closer to the people through pop-up and mobile clinics and provision of transport and ensuring confidentiality. There is a need to employ inclusive targeted non-conventional care interventions whilst dealing with complex problems as occur in rural and remote coastal regions.

Unintended consequences of communicating rapid COVID-19 vaccine policy changes- a qualitative study of health policy communication in Ontario, Canada.

BACKGROUND: The success of the COVID-19 vaccination roll-out depended on clear policy communication and guidance to promote and facilitate vaccine uptake. The rapidly evolving pandemic circumstances led to many vaccine policy amendments. The impact of changing policy on effective vaccine communication and its influence in terms of societal response to vaccine promotion are underexplored; this qualitative research addresses that gap within the extant literature. METHODS: Policy communicators and community leaders from urban and rural Ontario participated in semi-structured interviews (N = 29) to explore their experiences of COVID-19 vaccine policy communication. Thematic analysis was used to produce representative themes. RESULTS: Analysis showed rapidly changing policy was a barrier to smooth communication and COVID-19 vaccine roll-out. Continual amendments had unintended consequences, stimulating confusion, disrupting community outreach efforts and interrupting vaccine implementation. Policy changes were most disruptive to logistical planning and community engagement work, including community outreach, communicating eligibility criteria, and providing translated vaccine information to diverse communities. CONCLUSIONS: Vaccine policy changes that allow for prioritized access can have the unintended consequence of limiting communities' access to information that supports decision making. Rapidly evolving circumstances require a balance between adjusting policy and maintaining simple, consistent public health messages that can readily be translated into action. Information access is a factor in health inequality that needs addressing alongside access to vaccines.

Understanding the COVID-19 Vaccine Policy Terrain in Ontario Canada: A Policy Analysis of the Actors, Content, Processes, and Context.

(1) Background: Canada had a unique approach to COVID-19 vaccine policy making. The objective of this study was to understand the evolution of COVID-19 vaccination policies in Ontario, Canada, using the policy triangle framework. (2) Methods: We searched government websites and social media to identify COVID-19 vaccination policies in Ontario, Canada, which were posted between 1 October 2020, and 1 December 2021. We used the policy triangle framework to explore the policy actors, content, processes, and context. (3) Results: We reviewed 117 Canadian COVID-19 vaccine policy documents. Our review found that federal actors provided guidance, provincial actors made actionable policy, and community actors adapted policy to local contexts. The policy processes aimed to approve and distribute vaccines while continuously updating policies. The policy content focused on group prioritization and vaccine scarcity issues such as the delayed second dose and the mixed vaccine schedules. Finally, the policies were made in the context of changing vaccine science, global and national vaccine scarcity, and a growing awareness of the inequitable impacts of pandemics on specific communities. (4) Conclusions: We found that the triad of vaccine scarcity, evolving efficacy and safety data, and social inequities all contributed to the creation of vaccine policies that were difficult to efficiently communicate to the public. A lesson learned is that the need for dynamic policies must be balanced with the complexity of effective communication and on-the-ground delivery of care.

Psychometric evaluation of the hope, agency and opportunity (HAO); a brief measure of mental health recovery.

BACKGROUND: The development of safe and effective mental health services is a priority. This requires valid measures of personal recovery, yet these tools are not embedded in routine clinical practice. Brief "patient reported measures" are most likely to be acceptable to service-users and clinicians. The 4-item "Hope, Agency and Opportunity" (HAO) was co-produced to assess recovery outcomes and experience of mental health services. AIM: To evaluate the psychometric properties of the HAO. METHOD: A clinical sample from secondary healthcare services and a non-clinical sample were assessed at baseline and two weeks, on measures of personal recovery. RESULTS: Factor analysis indicated goodness of fit for the HAO with both clinical and non-clinical samples. The measure demonstrated acceptable internal consistency, moderate to strong construct validity and substantial test-retest reliability over two weeks. CONCLUSIONS: The HAO demonstrates satisfactory psychometric properties. Co-production of the measure confers clinical credibility. The brevity of the tool means it can be incorporated into routine clinical practice to drive improvements in service quality.

Defective epithelial barrier function in asthma.

BACKGROUND: Asthma is a complex disease involving gene and environment interactions. Although atopy is a strong predisposing risk factor for asthma, local tissue susceptibilities are required for disease expression. The bronchial epithelium forms the interface with the external environment and is pivotally involved in controlling tissue homeostasis through provision of a physical barrier controlled by tight junction (TJ) complexes. OBJECTIVES: To explain the link between environment exposures and airway vulnerability, we hypothesized that epithelial TJs are abnormal in asthma, leading to increased susceptibility to environmental agents. METHODS: Localization of TJs in bronchial biopsies and differentiated epithelial cultures was assessed by electron microscopy or immunostaining. Baseline permeability and the effect of cigarette smoke and growth factor were assessed by measurement of transepithelial electrical resistance and passage of fluorescently labeled dextrans. RESULTS: By using immunostaining, we found that bronchial biopsies from asthmatic subjects displayed patchy disruption of TJs. In differentiated bronchial epithelial cultures, TJ formation and transepithelial electrical resistance were significantly lower (P < .05) in cultures from asthmatic donors (n = 43) than from normal controls (n = 40) and inversely correlated with macromolecular permeability. Cultures from asthmatic donors were also more sensitive to disruption by cigarette smoke extract. Epidermal growth factor enhanced basal TJ formation in cultures from asthmatic subjects (P < .01) and protected against cigarette smoke-induced barrier disruption (P < .01). CONCLUSIONS: Our results show that the bronchial epithelial barrier in asthma is compromised. This defect may facilitate the passage of allergens and other agents into the airway tissue, leading to immune activation and may thus contribute to the end organ expression of asthma.

CD31 delays phagocyte membrane repolarization to promote efficient binding of apoptotic cells.

Homophilic ligation of CD31, a member of the Ig superfamily of adhesion receptors, promotes macrophage clearance of apoptotic leukocytes by a mechanism hitherto not described. In studying CD31-dependent regulation of beta1-integrin binding of fibronectin-coated Latex beads, we discovered a role for the voltage-gated potassium channel ether-à-go-go-related gene (ERG) as a downstream effector of CD31 signaling. ERG was identified by tandem mass spectrometry as a 140-kDa protein, which was selectively modified with biotin following the targeted delivery of a biotin-transfer reagent to CD31 using Fab fragments of an anti-CD31 mAb. Similar results were obtained with macrophages but not K562 cells, expressing a truncated cytoplasmic tail of CD31, which failed to regulate bead binding. Colocalization of CD31 with ERG was confirmed by immunofluorescence for K562 cells and macrophages. We now demonstrate that the resting membrane potential of macrophages is depolarized on contact with apoptotic cells and that CD31 inhibits the ERG current, which would otherwise function to repolarize. Sustained depolarization favored the firm binding of phagocytic targets, a prerequisite for efficient engulfment. Our results identify ERG as a downstream effector of CD31 in the regulation of integrin-dependent binding of apoptotic cells by macrophages.

CD31 promotes beta1 integrin-dependent engulfment of apoptotic Jurkat T lymphocytes opsonized for phagocytosis by fibronectin.

Phagocyte integrins, by binding "bridging" molecules, mediate the ingestion of late apoptotic cells and apoptotic bodies by mechanisms that remain obscure. We recently reported that human monocyte-derived macrophages capture viable and apoptotic human leukocytes through homophilic interactions involving CD31 and that CD31 then promotes the engulfment of apoptotic cells or the detachment of viable cells. We now report that CD31 homophilic interactions between phagocyte and target cells lead to activation of phagocyte alpha5beta1 integrin and the engulfment of apoptotic Jurkat T lymphocytes via a fibronectin (Fn) "bridge." Although Fn and serum served as an opsonin for beta1 integrin-dependent phagocytosis of apoptotic leukemic T cells, they failed to do so for neutrophils. Given the complexities and inherent variability of working with primary cells, we have refined our model to show that ligation of CD31 on THP-1 macrophages also regulates beta1 integrin-dependent phagocytosis of Fn-coated Latex beads. Thus, selective "tethering" of apoptotic leukocytes by phagocyte CD31 not only discriminates dying from viable cells but also selectively activates phagocyte integrins for the engulfment of apoptotic cells.

Promoting apoptosis in disease management: a panacea or Trojan horse?

In our enthusiasm to advocate apoptosis as a therapeutic strategy for the management of disease we need to be mindful that the clearance of apoptotic cells is itself immunomodulatory and that it may not always be as benign or beneficial as we think. Indeed, the existence of free apoptotic cells in situ may potentially be pathological, and not necessarily physiological, and any attempt to promote apoptosis in the absence of an appropriate phagocytic response for the treatment of, for example, inflammation or cancer might exacerbate or initiate an autoimmune pathology.

Rheumatoid fibroblast-like synoviocytes overexpress the chemokine stromal cell-derived factor 1 (CXCL12), which supports distinct patterns and rates of CD4+ and CD8+ T cell migration within synovial tissue.

OBJECTIVE: A characteristic feature of the inflammatory infiltrate in rheumatoid arthritis is the segregation of CD4 and CD8 T lymphocyte subsets into distinct microdomains within the inflamed synovium. The aim of this study was to test the hypothesis that chemokines in general and stromal cell-derived factor 1 (SDF-1; CXCL12) in particular are responsible for generating this distinctive microcompartmentalization. METHODS: We examined how synovial CD4/CD8 T cell subsets interacted in coculture assays with fibroblasts derived from chronic inflammatory synovial lesions and normal synovial tissue as well as from fetal lung and adult skin. We used the ability of T cells to migrate beneath fibroblasts (a process called pseudoemperipolesis) as an in vitro marker of T cell accumulation within synovial tissue. RESULTS: Rheumatoid fibroblast-like synoviocytes (FLS) displayed a unique ability to support high levels of CD4 and CD8 T cell pseudoemperipolesis. Nonrheumatoid FLS as well as fetal lung fibroblasts supported low levels of pseudoemperipolesis, while skin-derived fibroblasts were unable to do so. CD8 T cells migrated under fibroblasts more efficiently and at a higher velocity than CD4 T cells, a feature that was intrinsic to CD8 T cells. Rheumatoid fibroblasts constitutively produced high levels of SDF-1 (CXCL12), which was functionally important, since blocking studies showed reductions in T cell pseudoemperipolesis to levels seen in nonrheumatoid FLS. Rheumatoid fibroblasts also constitutively produced high levels of vascular cell adhesion molecule 1 (VCAM-1; CD106), but this did not contribute to T cell pseudoemperipolesis, unlike the case for B cells, which require SDF-1 (CXCL12)-CXCR4 and CD49d-VCAM-1 (CD106) interactions. Importantly, only combinations of rheumatoid FLS and rheumatoid-derived synovial fluid T cells supported pseudoemperipolesis when examined ex vivo, confirming the in vivo relevance of these findings. CONCLUSION: These studies demonstrate that features intrinsic to both fibroblasts (the production of SDF-1) and CD8/CD4 T cells (the expression of CXCR4) are responsible for the characteristic pattern of T lymphocyte accumulation seen in the rheumatoid synovium. These findings suggest that the SDF-1/CXCR4 ligand/receptor pair is likely to play an important functional role in T lymphocyte accumulation and positioning within the rheumatoid synovium.