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BackgroundImproving clinical reasoning skills—the thought processes used by clinicians to formulate appropriate questions and diagnoses—is essential for reducing missed diagnostic opportunities. The electronic Clinical Reasoning Educational Simulation Tool (eCREST) was developed to improve the clinical reasoning of future physicians. A feasibility trial demonstrated acceptability and potential impacts; however, the processes by which students gathered data were unknown. ObjectiveThis study aims to identify the data gathering patterns of final year medical students while using eCREST and how eCREST influences the patterns. MethodsA mixed methods design was used. A trial of eCREST across 3 UK medical schools (N=148) measured the potential effects of eCREST on data gathering. A qualitative think-aloud and semistructured interview study with 16 medical students from one medical school identified 3 data gathering strategies: Thorough, Focused, and Succinct. Some had no strategy. Reanalysis of the trial data identified the prevalence of data gathering patterns and compared patterns between the intervention and control groups. Patterns were identified based on 2 variables that were measured in a patient case 1 month after the intervention: the proportion of Essential information students identified and the proportion of irrelevant information gathered (Relevant). Those who scored in the top 3 quartiles for Essential but in the lowest quartile for Relevant displayed a Thorough pattern. Those who scored in the top 3 quartiles for Relevant but in the lowest quartile for Essential displayed a Succinct pattern. Those who scored in the top 3 quartiles on both variables displayed a Focused pattern. Those whose scores were in the lowest quartile on both variables displayed a Nonspecific pattern. ResultsThe trial results indicated that students in the intervention group were more thorough than those in the control groups when gathering data. The qualitative data identified data gathering strategies and the mechanisms by which eCREST influenced data gathering. Students reported that eCREST promoted thoroughness by prompting them to continuously reflect and allowing them to practice managing uncertainty. However, some found eCREST to be less useful, and they randomly gathered information. Reanalysis of the trial data revealed that the intervention group was significantly more likely to display a Thorough data gathering pattern than controls (21/78, 27% vs 6/70, 9%) and less likely to display a Succinct pattern (13/78, 17% vs 20/70, 29%; χ23=9.9; P=.02). Other patterns were similar across groups. ConclusionsQualitative data suggested that students applied a range of data gathering strategies while using eCREST and that eCREST encouraged thoroughness by continuously prompting the students to reflect and manage their uncertainty. Trial data suggested that eCREST led students to demonstrate more Thorough data gathering patterns. Virtual patients that encourage thoroughness could help future physicians avoid missed diagnostic opportunities and enhance the delivery of clinical reasoning teaching.

BackgroundSocial media is commonly used in public health interventions to promote cancer screening and early diagnosis, as it can rapidly deliver targeted public health messages to large numbers of people. However, there is currently little understanding of the breadth of social media interventions and evaluations, whether they are effective, and how they might improve outcomes. ObjectiveThis scoping review aimed to map the evidence for social media interventions to improve cancer screening and early diagnosis, including their impact on behavior change and how they facilitate behavior change. MethodsFive databases and the grey literature were searched to identify qualitative and quantitative evaluations of social media interventions targeting cancer screening and early diagnosis. Two reviewers independently reviewed each abstract. Data extraction was carried out by one author and verified by a second author. Data on engagement was extracted using an adapted version of the key performance indicators and metrics related to social media use in health promotion. Insights, exposure, reach, and differing levels of engagement, including behavior change, were measured. The behavior change technique taxonomy was used to identify how interventions facilitated behavior change. ResultsOf the 23 publications and reports included, the majority (16/23, 70%) evaluated national cancer awareness campaigns (eg, breast cancer awareness month). Most interventions delivered information via Twitter (13/23, 57%), targeted breast cancer (12/23, 52%), and measured exposure, reach, and low- to medium-level user engagement, such as number of likes (9/23, 39%). There were fewer articles about colorectal and lung cancer than about breast and prostate cancer campaigns. One study found that interventions had less reach and engagement from ethnic minority groups. A small number of articles (5/23, 22%) suggested that some types of social media interventions might improve high-level engagement, such as intended and actual uptake of screening. Behavior change techniques, such as providing social support and emphasizing the consequences of cancer, were used to engage users. Many national campaigns delivered fundraising messages rather than actionable health messages. ConclusionsThe limited evidence suggests that social media interventions may improve cancer screening and early diagnosis. Use of evaluation frameworks for social media interventions could help researchers plan more robust evaluations that measure behavior change. We need a greater understanding of who engages with these interventions to know whether social media can be used to reduce some health inequalities in cancer screening and early diagnosis. International Registered Report Identifier (IRRID)RR2-10.1136/bmjopen-2019-033592

Introduction Vaccine-preventable respiratory infections (VPRI) including those caused by Streptococcus pneumoniae, influenza, respiratory syncytial virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pose substantial challenges to health and social care systems. In the UK, routine adult respiratory vaccination programs are in place. The objective of this article is to review the current evidence on the impact of four seasonal VPRIs in adults risk group definitions and to explore the strengths and limitations of current recommendations, and to identify evidence gaps for further research.Areas covered Relevant evidence on UK data from surveillance systems, observational studies and publicly available government documents is collated and reviewed, as well as selected global data.Expert opinion Disparities exist between adult risk group categories for different respiratory vaccination programs as defined in the current vaccination guidance. The burden of multiple respiratory pathogens signifies importance of routine multi-pathogen testing with the need for a resilient and large-scale national surveillance system. Further understanding of epidemiological trends and disease burden will help guide decision-making and planning of targeted strategies for disease prevention and control. Addressing inequalities in disease burden and vaccine coverage particularly in clinical risk groups, and promoting equitable vaccine access remain a priority.

Abstract Background Vaccination uptake is a complex behavior, influenced by numerous factors. Behavioral science theories are commonly used to explain the psychosocial determinants of an individual’s health behavior. This study examined the behavioural, cognitive, and emotional determinants of COVID-19 vaccination intention based on well-established theoretical models: Acceptance and Commitment Therapy (ACT), Capability, Opportunity, Motivation, and Behaviour (COM-B) and the Health Belief Model (HBM). Additionally, it examined the mediating role of institutional trust in the relationship between determinants of these models and vaccination intentions. Methods A cross-sectional study was conducted from January to May 2022, where university students in Cyprus completed an online survey. Results A total of 484 university students completed the online survey, with 23.8% reporting being vaccinated with fewer than three vaccination doses and/or no intention to vaccinate further. Hierarchical logistic regression analysis showed that higher scores in institutional trust, perceived severity, motivation, physical and psychological capability were significantly associated with higher odds of intending to vaccinate. Higher psychological flexibility and not being infected with COVID-19 were also associated with higher odds of vaccination intention, but not in the final model when all determinants were included. Additionally, significant indirect effects of psychological and physical capability, motivation and perceived severity on vaccination intention were found to be mediated by institutional trust. Conclusions When tackling COVID-19 vaccination hesitancy, behavioural, cognitive, and emotional aspects should be considered. Stakeholders and policymakers are advised to implement targeted vaccination programs in young people while at the same time building trust and improving their capabilities and motivation towards getting vaccinated.

Chronic kidney disease (CKD) is the progressive loss of kidney function/structure over a period of at least 3 months. It is characterised histologically by the triad of cell loss, inflammation and fibrosis. This literature review focuses on the forms of cell death that trigger downstream inflammation and fibrosis, collectively called regulated cell death (RCD) pathways. Discrete forms of RCD have emerged as central mediators of CKD pathology. In particular, pathways of regulated necrosis – including mitochondrial permeability transition pore (mPTP)-mediated necrosis, necroptosis, ferroptosis and pyroptosis – have been shown to mediate kidney pathology directly or through the release of danger signals that trigger a pro-inflammatory response, further amplifying tissue injury in a cellular process called necroinflammation. Despite accumulating evidence in pre-clinical models, no clinical studies have yet targeted these RCD modes in human CKD. The review summarizes recent advances in our understanding of RCD pathways in CKD, looks at inter-relations between the pathways (with the emphasis on propagation of death signals) and the evidence for therapeutic targeting of molecules in the RCD pathways to prevent or treat CKD.

Abstract Undoubtedly, the mental health of healthcare workers (HCWs) was negatively affected because of caring for patients during the COVID-19 pandemic. However, literature is limited on mapping the challenges and needs of HCWs during COVID-19 pandemic. A widely used framework in public health for mapping evidence includes the socio-ecological models, suggesting behavior can be influenced by individual, interpersonal, organizational, and community factors. The aim of this rapid scoping review was to use the socio-ecological model to map and compile lessons learnt from the literature regarding primarily the challenges and needs and secondly available psychological interventions for HCWs caring for COVID-19 patients. PubMed, CINAHL and Scopus databases were searched, with 21 studies finally included examining challenges and needs of HCWs and 18 studies presenting psychological interventions. Organizational-level challenges and needs such as inadequate staff preparation and supplies of protective equipment, flexible work policies and paid rest periods were the most reported. Individual-level challenges and needs included COVID-19-related fears and reduced mental health, whereas interpersonal-related needs included support provision. Community-level challenges included societal stigma. Certain psychological interventions were found to be promising for HCWs, but these were utilized to address only individual-level challenges and needs. Given that well-being entails an interaction of factors, multi-level interventions addressing multiple socio-ecological levels (interpersonal, organizational, community) and that place HCWs in their social context should be administrated to increase and maintain intervention’ effects long-term and possibly aid in better coping with future pandemics.

Abstract Background In Indonesia, the adoption of telepharmacy was propelled by the COVID-19 pandemic, prompting the need for a user-friendly application to support both the general population and pharmacists in accessing healthcare services. Therefore, this study aimed to evaluate usability and user feedback of a pioneering telepharmacy application known as Tanya Obat (translating to “Ask about Medications”) in Indonesia, from the perspectives of the general population and pharmacists. Methods A mixed-methods sequential study was conducted with the early-stage Tanya Obat application in Bandung City. Participants, including the general population and pharmacists, were instructed to use the application for a week. Questionnaires for the general population and pharmacists were distributed from March to May and February to June 2023, respectively. The System Usability Scale questionnaire was adopted to describe usability of the developed application. Further exploration of the quantitative results required collecting open-ended feedback to assess the impressions of the participants, difficulties encountered, and desired features for enhanced user-friendliness. The collected statements were summarized and clustered using thematic analysis. Subsequently, the association between the characteristics of participants and perceived usability was determined with the Chi-square test. Result A total of 176 participants, comprising 100 individuals from the general population and 76 pharmacists, engaged in this study. In terms of usability, the questionnaire showed that Tanya Obat application was on the borderline of acceptability, with mean scores of 63.4 and 64.1 from the general population and pharmacists, respectively. Additionally, open-ended feedback targeted at achieving a more compelling user experience was categorized into two themes, including concerns regarding the functionality of certain features and recommendations for improved visual aesthetics and bug fixes. No significant associations were observed between the characteristics of participants and perceived usability (p-value > 0.05). Conclusion The results showed that the perceived usability of Tanya Obat developed for telepharmacy was below average. Therefore, feature optimizations should be performed to facilitate usability of this application in Indonesia.

Introduction Pneumococcal disease (PD) significantly contributes to morbidity and mortality, carrying substantial economic and public health burden. This article is a targeted review of evidence for pneumococcal vaccination in the UK, the definitions of groups at particular risk of PD and vaccine effectiveness. Areas covered Relevant evidence focusing on UK data from surveillance systems, randomized controlled trials, observational studies and publicly available government documents is collated and reviewed. Selected global data are included where appropriate. Expert opinion National vaccination programs have reduced the incidence of vaccine-type PD, despite the rising prominence of non-vaccine serotypes in the UK. The introduction of higher-valency conjugate vaccines provides an opportunity to improve protection against PD for adults in risk groups. Several incentives are in place to encourage general practitioners to vaccinate risk groups, but uptake is low-suboptimal particularly among at-risk individuals. Wider awareness and understanding among the public and healthcare professionals may increase vaccination uptake and coverage. National strategies targeting organizational factors are urgently needed to achieve optimal access to vaccines. Finally, identifying new risk factors and approaches to risk assessment for PD are crucial to ensure those at risk of PD can benefit from pneumococcal vaccination.

Abstract Perioperative immune checkpoint inhibitor (ICI) trials for intermediate high-risk clear cell renal cell carcinoma (ccRCC) have failed to consistently demonstrate improved patient outcomes. These unsuccessful ICI trials suggest that the tumour infiltrating immunophenotypes, termed here as the immune cell types, states and their spatial location within the tumour microenvironment (TME), were unfavourable for ICI treatment. Defining the tumour infiltrating immune cells may assist with the identification of predictive immunophenotypes within the TME that are favourable for ICI treatment. To define the immunophenotypes within the ccRCC TME, fresh para-tumour (pTME, n = 2), low-grade (LG, n = 4, G1-G2) and high-grade (HG, n = 4, G3-G4) tissue samples from six patients with ccRCC presenting at a tertiary referral hospital underwent spatial transcriptomics sequencing (ST-seq). Within the generated ST-seq datasets, immune cell types and states, termed here as exhausted/pro-tumour state or non-exhausted/anti-tumour state, were identified using multiple publicly available single-cell RNA and T-cell receptor sequencing datasets as references. HG TMEs revealed abundant exhausted/pro-tumour immune cells with no consistent increase in expression of PD-1, PD-L1 and CTLA4 checkpoints and angiogenic genes. Additional HG TME immunophenotype characteristics included: pro-tumour tissue-resident monocytes with consistently increased expression of HAVCR2 and LAG3 checkpoints; an exhausted CD8+ T cells sub-population with stem-like progenitor gene expression; and pro-tumour tumour-associated macrophages and monocytes within the recurrent TME with the expression of TREM2. Whilst limited by a modest sample size, this study represents the largest ST-seq dataset on human ccRCC. Our study reveals that high-risk ccRCC TMEs are infiltrated by exhausted/pro-tumour immunophenotypes lacking specific checkpoint gene expression confirming that HG ccRCC TME are immunogenic but not ICI favourable.

Hypoxia is the key pathobiological trigger of tubular oxidative stress and cell death that drives the transition of acute kidney injury (AKI) to chronic kidney disease (CKD). The mitochondrial-rich proximal tubular epithelial cells (PTEC) are uniquely sensitive to hypoxia and thus, are pivotal in propagating the sustained tubular loss of AKI-to-CKD transition. Here, we examined the role of PTEC-derived small extracellular vesicles (sEV) in propagating the ‘wave of tubular death’.Ex vivo patient-derived PTEC were cultured under normoxia (21 % O2) and hypoxia (1 % O2) on Transwell inserts for isolation and analysis of sEV secreted from apical versus basolateral PTEC surfaces. Increased numbers of sEV were secreted from the apical surface of hypoxic PTEC compared with normoxic PTEC. No differences in basolateral sEV numbers were observed between culture conditions. Biological pathway analysis of hypoxic-apical sEV cargo identified distinct miRNAs linked with cellular injury pathways. In functional assays, hypoxic-apical sEV selectively induced ferroptotic cell death (↓glutathione peroxidase-4, ↑lipid peroxidation) in autologous PTEC compared with normoxic-apical sEV. The addition of ferroptosis inhibitors, ferrostatin-1 and baicalein, attenuated PTEC ferroptosis. RNAse A pretreatment of hypoxic-apical sEV also abrogated PTEC ferroptosis, demonstrating a role for sEV RNA in ferroptotic ‘wave of death’ signalling. In line with these in vitro findings, in situ immunolabelling of diagnostic kidney biopsies from AKI patients with clinical progression to CKD (AKI-to-CKD transition) showed evidence of ferroptosis propagation (increased numbers of ACSL4+ PTEC), while urine-derived sEV (usEV) from these ‘AKI-to-CKD transition’ patients triggered PTEC ferroptosis (↑lipid peroxidation) in functional studies.Our data establish PTEC-derived apical sEV and their intravesicular RNA as mediators of tubular lipid peroxidation and ferroptosis in hypoxic kidney injury. This concept of how tubular pathology is propagated from the initiating insult into a ‘wave of death’ provides novel therapeutic check-points for targeting AKI-to-CKD transition.

Abstract This study aims to understand the levels of fear experienced by individuals regarding future pandemics and/or epidemics among the general population of Cyprus and comprehensively examine the diverse factors that influence this perceived fear. The cross-sectional study was conducted from October 1st, 2022, to February 19th, 2023. A proportionate quota sampling method was used for the recruitment, by recruiting a fixed number of participants from each age group, sex, and place of residence. The study collected information on sociodemographic and health-related characteristics, health literacy, trust, COVID-19 vaccination information, and perceived fear of future epidemics and/or pandemics using a self-administered questionnaire. The survey included 1075 participants, with 53.7% of them reporting fear of future pandemics. Logistic regression analysis revealed that women (OR = 2.37, 95% CI 1.78, 3.16) and individuals vaccinated against COVID-19 (OR = 1.57, 95% CI 1.02, 2.43) were significantly more likely to experience fear of future pandemics. Moreover, higher levels of trust (OR = 1.04, 95% CI 1.02, 1.06) and higher health literacy (OR = 1.05, 95% CI 1.03, 1.08) were associated with an increased likelihood of fearing future pandemics. Conversely, unemployment (OR = 0.30, 95% CI 0.13, 0.65) and having a postgraduate education decreased the likelihood of fearing future pandemics (OR = 0.56, 95% CI 0.34, 0.90). The linear regression model revealed that older age (β = − 0.10, 95% CI − 0.14, − 0.05) was negatively associated with a higher score of fear regarding future pandemics. Conversely, being in a vulnerable group (β = 2.02, 95% CI 0.75, 3.28) and having at least one chronic disease (β = 1.76, 95% CI 0.68, 2.84) showed positive associations with increased fear of future epidemics and/or pandemics. The findings emphasize the need for relevant authorities to prioritize mental health and disseminate information in a manner that avoids spreading fear and panic, particularly among vulnerable population groups.

Abstract Recombinant vaccines against invasive meningococcal disease due to Neisseria meningitidis serogroup B (MenB) have shown substantial impact in reducing MenB disease in targeted populations. 4CMenB targets four key N. meningitidis protein antigens; human factor H binding protein (fHbp), Neisserial heparin binding antigen (NHBA), Neisseria adhesin A (NadA) and the porin A protein (PorA P1.4), with one or more of these expressed by most pathogenic MenB strains, while MenB-FHbp targets two distinct fHbp variants. While many countries recommend MenB immunisation in adults considered at high risk due to underlying medical conditions or immunosuppression, there are no recommendations for routine use in the general adult population. We reviewed the burden of MenB in adults, where, while incidence rates remain low (and far lower than in young children 50 years) and key aspects relating to duration of protection remain unclear. Although a broader adult MenB immunisation policy could provide greater protection of the adult population, additional data are required to support policy decision-making. Graphical Abstract

Abstract Background Learning tools using virtual patients can be used to teach clinical reasoning (CR) skills and overcome limitations of using face-to-face methods. However, the adoption of new tools is often challenging. The aim of this study was to explore UK medical educators’ perspectives of what influences the adoption of virtual patient learning tools to teach CR. Methods A qualitative research study using semi-structured telephone interviews with medical educators in the UK with control over teaching materials of CR was conducted. The Consolidated Framework for Implementation Research (CFIR), commonly used in healthcare services implementation research was adapted to inform the analysis. Thematic analysis was used to analyse the data. Results Thirteen medical educators participated in the study. Three themes were identified from the data that influenced adoption: the wider context (outer setting); perceptions about the innovation; and the medical school (inner context). Participants’ recognition of situations as opportunities or barriers related to their prior experiences of implementing online learning tools. For example, participants with experience of teaching using online tools viewed limited face-to-face placements as opportunities to introduce innovations using virtual patients. Beliefs that virtual patients may not mirror real-life consultations and perceptions of a lack of evidence for them could be barriers to adoption. Adoption was also influenced by the implementation climate of the setting, including positioning of CR in curricula; relationships between faculty, particularly where faculty were dispersed. Conclusions By adapting an implementation framework for health services, we were able to identify features of educators, teaching processes and medical schools that may determine the adoption of teaching innovations using virtual patients. These include access to face-to-face teaching opportunities, positioning of clinical reasoning in the curriculum, relationship between educators and institutions and decision-making processes. Framing virtual patient learning tools as additional rather than as a replacement for face-to-face teaching could reduce resistance. Our adapted framework from healthcare implementation science may be useful in future studies of implementation in medical education.

The COVID-19 pandemic involved a complex set of stressors affecting the health and well-being of the population. The understanding of the psychological processes that influence well-being in response to the pandemic and their interrelation is vital. A promising process in understanding the emotional impacts of these stressors is psychological flexibility. This study investigated the effect of psychological flexibility on well-being, both directly and indirectly, via mindfulness and coping strategies. A total of 334 Portuguese adults participated in this cross-sectional study. Participants were asked to complete an online questionnaire, including measures of psychological flexibility, well-being, mindfulness, and coping strategies. A multiple mediation model studied whether there are conditional indirect effects of mindfulness and coping strategies on well-being. The results showed statistically significant correlations between psychological flexibility, well-being, mindfulness, and coping strategies. Furthermore, we found that mindfulness and coping strategies partly mediate the relationship between psychological flexibility and well-being. Understanding the processes through which psychological flexibility influences well-being in a stressful context is important in comprehending the processes involved in an emotional reaction to a pandemic-like societal event. Mindfulness and coping are shown to be important processes to consider in understanding this phenomenon and designing future responses.

Abstract Background Identifying common factors that affect public adherence to COVID-19 containment measures can directly inform the development of official public health communication strategies. The present international longitudinal study aimed to examine whether prosociality, together with other theoretically derived motivating factors (self-efficacy, perceived susceptibility and severity of COVID-19, perceived social support) predict the change in adherence to COVID-19 containment strategies. Method In wave 1 of data collection, adults from eight geographical regions completed online surveys beginning in April 2020, and wave 2 began in June and ended in September 2020. Hypothesized predictors included prosociality, self-efficacy in following COVID-19 containment measures, perceived susceptibility to COVID-19, perceived severity of COVID-19 and perceived social support. Baseline covariates included age, sex, history of COVID-19 infection and geographical regions. Participants who reported adhering to specific containment measures, including physical distancing, avoidance of non-essential travel and hand hygiene, were classified as adherence. The dependent variable was the category of adherence, which was constructed based on changes in adherence across the survey period and included four categories: non-adherence, less adherence, greater adherence and sustained adherence (which was designated as the reference category). Results In total, 2189 adult participants (82% female, 57.2% aged 31–59 years) from East Asia (217 [9.7%]), West Asia (246 [11.2%]), North and South America (131 [6.0%]), Northern Europe (600 [27.4%]), Western Europe (322 [14.7%]), Southern Europe (433 [19.8%]), Eastern Europe (148 [6.8%]) and other regions (96 [4.4%]) were analyzed. Adjusted multinomial logistic regression analyses showed that prosociality, self-efficacy, perceived susceptibility and severity of COVID-19 were significant factors affecting adherence. Participants with greater self-efficacy at wave 1 were less likely to become non-adherence at wave 2 by 26% (adjusted odds ratio [aOR], 0.74; 95% CI, 0.71 to 0.77; P

Abstract Background Systematic reviews (SRs) are invaluable evidence syntheses, widely used in biomedicine and other scientific areas. Tremendous resources are being spent on the production and updating of SRs. There is a continuous need to automatize the process and use the workforce and resources to make it faster and more efficient. Methods Information gathered by previous EVBRES research was used to construct a questionnaire for round 1 which was partly quantitative, partly qualitative. Fifty five experienced SR authors were invited to participate in a Delphi study (DS) designed to identify the most promising areas and methods to improve the efficient production and updating of SRs. Topic questions focused on which areas of SRs are most time/effort/resource intensive and should be prioritized in further research. Data were analysed using NVivo 12 plus, Microsoft Excel 2013 and SPSS. Thematic analysis findings were used on the topics on which agreement was not reached in round 1 in order to prepare the questionnaire for round 2. Results Sixty percent (33/55) of the invited participants completed round 1; 44% (24/55) completed round 2. Participants reported average of 13.3 years of experience in conducting SRs (SD 6.8). More than two thirds of the respondents agreed/strongly agreed the following topics should be prioritized: extracting data, literature searching, screening abstracts, obtaining and screening full texts, updating SRs, finding previous SRs, translating non-English studies, synthesizing data, project management, writing the protocol, constructing the search strategy and critically appraising. Participants have not considered following areas as priority: snowballing, GRADE-ing, writing SR, deduplication, formulating SR question, performing meta-analysis. Conclusions Data extraction was prioritized by the majority of participants as an area that needs more research/methods development. Quality of available language translating tools has dramatically increased over the years (Google translate, DeepL). The promising new tool for snowballing emerged (Citation Chaser). Automation cannot substitute human judgement where complex decisions are needed (GRADE-ing). Trial registration Study protocol was registered at https://osf.io/bp2hu/ .

Measurement(s) COVID-19 Protocols, Restrictions • Health Behaviors • Personality and Behavioral Change, CTCAE • Emotion • Message Framing • Self-Determination Technology Type(s) Survey • Experiment Design Type Factor Type(s) COVID-19 Protocols, Restrictions • Health Behaviors • Loss-Gain Framing • Cognitive Reappraisal • Self-Determination Messaging Sample Characteristic - Organism Homo Sample Characteristic - Environment Daily Life Sample Characteristic - Location North America • South America • Africa • Australia • Europe • United Kingdom • Asia

Background: In times of unprecedented infectious disease threats, it is essential to understand how to increase individual protective behaviors and support for collective measures. The present study therefore examines factors associated with individual and collective pathways. Methods: Data was collected through an online survey from 4483 participants (70.8% female, M = 41.2 years) across 10 countries from April 15, 2020 to June 2, 2020 as part of the ''EUCLID'' project (https://euclid.dbvis.de). Structural equation modeling was used to examine individual and collective pathways across and within countries. Results: Overall, the adoption of individual protective behaviors and support for collective measures were high. Risk perception on the individual level and perceived effectiveness at the collective level were positively associated with both individual protective behaviors and support for collective measures. Furthermore, the model explained considerable variance in individual (40.7%) and collective protective behaviors (40.8%) and was largely replicated across countries. Conclusions: The study extends previous research by demonstrating that individual risk perception and perceived effectiveness of collective measures jointly affect individual protective health behaviors and support for collective measures. These findings highlight the need to jointly consider a variety of behavioral actions against infectious disease threats, acknowledging interactions between individual and collective pathways.

Vaccination attitudes and uptake can spread within social networks. This study aims to understand the perceived social contagion mechanisms of vaccination uptake in the context of COVID-19 pandemic. Eleven semi-structured interviews were conducted following a purposive sampling of three hesitant, three anti- COVID-19 vaccine and five pro- COVID-19 vaccine (27% females). Thematic Analysis suggested two general themes reflecting the type of contagion: 1) information contagion and 2) behavior contagion. Transcending these themes was the notion of ownership of choice/decision. Almost all participants used the media and experts as the main source of information regarding vaccination. They influenced – and they were being influenced by – friends and family members with whom they share similar traits and attitudes and have a close relationship of trust and intimacy. Also, being exposed to positive attitudes and beliefs toward vaccination and COVID-19 vaccines, enhanced vaccination behaviors. However, the vaccination decision-making process was not perceived as a passive process – there was ownership over the decisions made. This study highlights the perceived mechanisms of social contagion. It also suggests that the meaning individuals pose on their social world is crucial on their decision-making. Policymakers are advised to consider including social networks of individuals and trusted sources (i.e. healthcare providers) when delivering interventions or educational campaigns on vaccinations.

Abstract Objectives To outline the planning, development and optimisation of a psycho-educational behavioural intervention for patients on active surveillance for prostate cancer. The intervention aimed to support men manage active surveillance-related psychological distress. Methods The person-based approach (PBA) was used as the overarching guiding methodological framework for intervention development. Evidence-based methods were incorporated to improve robustness. The process commenced with data gathering activities comprising the following four components: • A systematic review and meta-analysis of depression and anxiety in prostate cancer • A cross-sectional survey on depression and anxiety in active surveillance • A review of existing interventions in the field • A qualitative study with the target audience The purpose of this paper is to bring these components together and describe how they facilitated the establishment of key guiding principles and a logic model, which underpinned the first draft of the intervention. Results The prototype intervention, named PROACTIVE, consists of six Internet-based sessions run concurrently with three group support sessions. The sessions cover the following topics: lifestyle (diet and exercise), relaxation and resilience techniques, talking to friends and family, thoughts and feelings, daily life (money and work) and information about prostate cancer and active surveillance. The resulting intervention has been trialled in a feasibility study, the results of which are published elsewhere. Conclusions The planning and development process is key to successful delivery of an appropriate, accessible and acceptable intervention. The PBA strengthened the intervention by drawing on target-user experiences to maximise acceptability and user engagement. This meticulous description in a clinical setting using this rigorous but flexible method is a useful demonstration for others developing similar interventions. Trial registration and Ethical Approval ISRCTN registered: ISRCTN38893965 . NRES Committee South Central – Oxford A. REC reference: 11/SC/0355

Abstract Inflammasomes are multiprotein platforms responsible for the release of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Mouse studies have identified inflammasome activation within dendritic cells (DC) as pivotal for driving tubulointerstitial fibrosis and inflammation, the hallmarks of chronic kidney disease (CKD). However, translation of this work to human CKD remains limited. Here, we examined the complex tubular cell death pathways mediating inflammasome activation in human kidney DC and, thus, CKD progression. Ex vivo patient-derived proximal tubular epithelial cells (PTEC) cultured under hypoxic (1% O2) conditions modelling the CKD microenvironment showed characteristics of ferroptotic cell death, including mitochondrial dysfunction, reductions in the lipid repair enzyme glutathione peroxidase 4 (GPX4) and increases in lipid peroxidation by-product 4-hydroxynonenal (4-HNE) compared with normoxic PTEC. The addition of ferroptosis inhibitor, ferrostatin-1, significantly reduced hypoxic PTEC death. Human CD1c+ DC activated in the presence of hypoxic PTEC displayed significantly increased production of inflammasome-dependent cytokines IL-1β and IL-18. Treatment of co-cultures with VX-765 (caspase-1/4 inhibitor) and MCC950 (NLRP3 inflammasome inhibitor) significantly attenuated IL-1β/IL-18 levels, supporting an NLRP3 inflammasome-dependent DC response. In line with these in vitro findings, in situ immunolabelling of human fibrotic kidney tissue revealed a significant accumulation of tubulointerstitial CD1c+ DC containing active inflammasome (ASC) specks adjacent to ferroptotic PTEC. These data establish ferroptosis as the primary pattern of PTEC necrosis under the hypoxic conditions of CKD. Moreover, this study identifies NLRP3 inflammasome signalling driven by complex tubulointerstitial PTEC-DC interactions as a key checkpoint for therapeutic targeting in human CKD.

Immunization programmes have been globally recognized as one of the most successful medical interventions against infectious diseases. Despite the proven efficacy and safety profiles of coronavirus disease 2019 (COVID-19) vaccines, there are still a substantial number of people who express vaccine hesitancy. Factors that influence vaccine decision-making are heterogenous, complex, and context specific and may be caused or amplified by uncontrolled online information or misinformation. With respect to COVID-19, the recent emergence of novel variants of concern that give rise to milder disease also drives vaccine hesitancy. Healthcare professionals remain one of the most trusted groups to advise and provide information to those ambivalent about COVID-19 vaccination and should be equipped with adequate resources and information as well as practical guidance to empower them to effectively discuss concerns. This article seeks to summarize the currently available information to address the most common concerns regarding COVID-19 vaccination.

Abstract Background Influenza surveillance systems vary widely between countries and there is no framework to evaluate national surveillance systems in terms of data generation and dissemination. This study aimed to develop and test a comparative framework for European influenza surveillance. Methods Surveillance systems were evaluated qualitatively in five European countries (France, Germany, Italy, Spain, and the United Kingdom) by a panel of influenza experts and researchers from each country. Seven surveillance sub-systems were defined: non-medically attended community surveillance, virological surveillance, community surveillance, outbreak surveillance, primary care surveillance, hospital surveillance, mortality surveillance). These covered a total of 19 comparable outcomes of increasing severity, ranging from non-medically attended cases to deaths, which were evaluated using 5 comparison criteria based on WHO guidance (granularity, timing, representativeness, sampling strategy, communication) to produce a framework to compare the five countries. Results France and the United Kingdom showed the widest range of surveillance sub-systems, particularly for hospital surveillance, followed by Germany, Spain, and Italy. In all countries, virological, primary care and hospital surveillance were well developed, but non-medically attended events, influenza cases in the community, outbreaks in closed settings and mortality estimates were not consistently reported or published. The framework also allowed the comparison of variations in data granularity, timing, representativeness, sampling strategy, and communication between countries. For data granularity, breakdown per risk condition were available in France and Spain, but not in the United Kingdom, Germany and Italy. For data communication, there were disparities in the timeliness and accessibility of surveillance data. Conclusions This new framework can be used to compare influenza surveillance systems qualitatively between countries to allow the identification of structural differences as well as to evaluate adherence to WHO guidance. The framework may be adapted for other infectious respiratory diseases.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the waning of immunity over time has necessitated the use of booster doses of original coronavirus disease 2019 (COVID-19) vaccines. This has also led to the development and implementation of variant-adapted messenger RNA (mRNA) vaccines that include an Omicron sub-lineage component in addition to the antigen based on the wild-type virus spike protein. Subsequent emergence of the recombinant XBB sub-lineages triggered the development of monovalent XBB-based variant-adapted mRNA vaccines, which are available for vaccination campaigns in late 2023. Misconceptions about new variant-adapted vaccines may exacerbate vaccine fatigue and drive the lack of vaccine acceptance. This article aims to address common concerns about the development and use of COVID-19 variant-adapted mRNA vaccines that have emerged as SARS-CoV-2 has continued to evolve.

Abstract Background Use of virtual patient educational tools could fill the current gap in the teaching of clinical reasoning skills. However, there is a limited understanding of their effectiveness. The aim of this study was to synthesise the evidence to understand the effectiveness of virtual patient tools aimed at improving undergraduate medical students’ clinical reasoning skills. Methods We searched MEDLINE, EMBASE, CINAHL, ERIC, Scopus, Web of Science and PsycINFO from 1990 to January 2022, to identify all experimental articles testing the effectiveness of virtual patient educational tools on medical students’ clinical reasoning skills. Quality of the articles was assessed using an adapted form of the MERSQI and the Newcastle–Ottawa Scale. A narrative synthesis summarised intervention features, how virtual patient tools were evaluated and reported effectiveness. Results The search revealed 8,186 articles, with 19 articles meeting the inclusion criteria. Average study quality was moderate (M = 6.5, SD = 2.7), with nearly half not reporting any measurement of validity or reliability for their clinical reasoning outcome measure (8/19, 42%). Eleven articles found a positive effect of virtual patient tools on reasoning (11/19, 58%). Four reported no significant effect and four reported mixed effects (4/19, 21%). Several domains of clinical reasoning were evaluated. Data gathering, ideas about diagnosis and patient management were more often found to improve after virtual patient use (34/47 analyses, 72%) than application of knowledge, flexibility in thinking and problem-solving (3/7 analyses, 43%). Conclusions Using virtual patient tools could effectively complement current teaching especially if opportunities for face-to-face teaching or other methods are limited, as there was some evidence that virtual patient educational tools can improve undergraduate medical students’ clinical reasoning skills. Evaluations that measured more case specific clinical reasoning domains, such as data gathering, showed more consistent improvement than general measures like problem-solving. Case specific measures might be more sensitive to change given the context dependent nature of clinical reasoning. Consistent use of validated clinical reasoning measures is needed to enable a meta-analysis to estimate effectiveness.

IntroductionWe aim to understand the factors that drive citizens of different countries to adhere to recommended self-protective behaviors during the COVID-19 pandemic.MethodsSurvey data was obtained through the COVID-19 Impact project. We selected countries that presented a sufficiently complete time series and a statistically relevant sample for running the analysis: Cyprus, Germany, Greece, Ireland, Latvia, Spain, Switzerland, the United Kingdom, and the United States of America. To identify country-specific differences in self-protective behaviors, we used previous evidence and change-point detection analysis to establish variations across participating countries whose effect was then assessed by means of interrupted series analysis.ResultsA high level of compliance with health and governmental authorities' recommendations were generally observed in all included countries. The level of stress decreased near the period when countries such as Cyprus, Greece or the United Kingdom relaxed their prevention behavior recommendations. However, this relaxation of behaviors did not occur in countries such as Germany, Ireland, or the United States. As observed in the change-point detection analysis, when the daily number of recorded COVID-19 cases decreased, people relaxed their protective behaviors (Cyprus, Greece, Ireland), although the opposite trend was observed in Switzerland.DiscussionCOVID-19 self-protective behaviors were heterogeneous across countries examined. Our findings show that there is probably no single winning strategy for exiting future health crises, as similar interventions, aimed to promote self-protective behaviors, may be received differently depending on the specific population groups and on the particular geographical context in which they are implemented.

Despite the occurrence of several hepatitis A (hepA) and hepatitis B (hepB) outbreaks in Europe in the last few decades, not all European countries have implemented hepA and hepB vaccinations in their national immunization programs, especially for adults at risk for hepA and/or hepB infection, such as men who have sex with men or patients with chronic liver disease. Currently, little is known on the attitudes of European healthcare professionals (HCPs) towards hepA and hepB vaccinations for at-risk adults. We conducted an online survey among HCPs in Germany, Spain, and the United Kingdom to assess their awareness of and adherence to their national hepA and hepB vaccination guidelines for at-risk adults. Among the 698 HCPs who took the survey, most (91.1%) were familiar with their national vaccination recommendations and always followed them or followed them most of the time when advising or prescribing hepA or hepB vaccines. Major and moderate barriers for recommending or administering such vaccines were the non-disclosure of risk factors by the patient (53.0–57.6%) and the patient’s lack of motivation or knowledge about the risk of the disease (50.3–52.9%). These results may help inform strategies to improve and accelerate hepA and hepB vaccination in European at-risk adults.

Abstract. Introduction: Following the onset of the COVID-19 pandemic, most countries imposed strict governmental lockdowns. Research investigating the psychological impact of pandemic-induced lockdowns is accumulating, though to date no study has examined the psychological health and associated parameters of well-being in countries that underwent additional lockdowns as the pandemic continued into resurgence “waves.” Aim: The present study provides an overview of the psychological impact of COVID-19 across the two lockdowns in the Cypriot population. Methods: In total, 957 participants completed an online survey during the first lockdown, 134 of whom completed a similar survey again during the second lockdown. The outcomes assessed included stress, positive and negative affect, and well-being. Results: The results indicated no population-wide severe reactions in the participants. Repeated measures analyses showed similar mental health levels during both the first and the second lockdowns. Further inspection of participants’ scores indicated that, for all mental health variables, approximately half of the participants improved, while the other half deteriorated. Discussion: Perceived social support and psychological flexibility predicted most psychological outcomes during both lockdowns. Further research is necessary to understand the continuing effects of the pandemic and associated lockdowns on mental health.

Abstract. Background: The COVID-19 pandemic is a massive health crisis that has exerted enormous physical and psychological pressure. Mental healthcare for healthcare workers (HCWs) should receive serious consideration. This study served to determine the mental-health outcomes of 1,556 HCWs from 45 countries who participated in the COVID-19 IMPACT project, and to examine the predictors of the outcomes during the first pandemic wave. Methods: Outcomes assessed were self-reported perceived stress, depression symptom, and sleep changes. The predictors examined included sociodemographic factors and perceived social support. Results: The results demonstrated that half of the HCWs had moderate levels of perceived stress and symptoms of depression. Half of the HCWs (n = 800, 51.4%) had similar sleeping patterns since the pandemic started, and one in four slept more or slept less. HCWs reported less perceived stress and depression symptoms and higher levels of perceived social support than the general population who participated in the same project. Predictors associated with higher perceived stress and symptoms of depression among HCWs included female sex, not having children, living with parents, lower educational level, and lower social support. Discussion: The need for establishing ways to mitigate mental-health risks and adjusting psychological interventions and support for HCWs seems to be significant as the pandemic continues.

During the COVID-19 pandemic, immunization programs for other respiratory infections, notably influenza continued worldwide but attracted less public or political attention than COVID-19 vaccinations. Due to non-pharmaceutical intervention measures the global influenza burden decreased substantially; but with lifting of restrictions a rebound in other respiratory virus pathogens is both plausible and likely. This article discusses lessons identified from the UK and USA, and provides recommendations for future influenza vaccination programs in light of emerging data from the southern hemisphere and the need for harmonization with COVID-19 vaccination, focusing on operational delivery and messaging to practitioners and the public.

Clear cell renal cell carcinoma (ccRCC) is globally the most prevalent renal cancer. The cells of origin in ccRCC have been identified as proximal tubular epithelial cells (PTEC); however, the transcriptomic pathways resulting in the transition from normal to malignant PTEC state have remained unclear. Immunotherapy targeting checkpoints have revolutionized the management of ccRCC, but a sustained clinical response is achieved in only a minority of ccRCC patients. This indicates that our understanding of the mechanisms involved in the malignant transition and resistance to immune checkpoint therapy in ccRCC is unclear. This review examines recent single-cell transcriptomics studies of ccRCC to clarify the transition of PTEC in ccRCC development, and the immune cell types, states, and interactions that may limit the response to targeted immune therapy, and finally suggests stromal cells as key drivers in recurrent and locally invasive ccRCC. These and future single-cell transcriptomics studies will continue to clarify the cellular milieu in the ccRCC microenvironment, thus defining actional clinical, therapeutic, and prognostic characteristics of ccRCC.

Available transcriptomes of the mammalian kidney provide limited information on the spatial interplay between different functional nephron structures due to the required dissociation of tissue with traditional transcriptome-based methodologies. A deeper understanding of the complexity of functional nephron structures requires a non-dissociative transcriptomics approach, such as spatial transcriptomics sequencing (ST-seq). We hypothesize that the application of ST-seq in normal mammalian kidneys will give transcriptomic insights within and across species of physiology at the functional structure level and cellular communication at the cell level. Here, we applied ST-seq in six mice and four human kidneys that were histologically absent of any overt pathology. We defined the location of specific nephron structures in the captured ST-seq datasets using three lines of evidence: pathologist's annotation, marker gene expression, and integration with public single-cell and/or single-nucleus RNA-sequencing datasets. We compared the mouse and human cortical kidney regions. In the human ST-seq datasets, we further investigated the cellular communication within glomeruli and regions of proximal tubules–peritubular capillaries by screening for co-expression of ligand–receptor gene pairs. Gene expression signatures of distinct nephron structures and microvascular regions were spatially resolved within the mouse and human ST-seq datasets. We identified 7,370 differentially expressed genes (padj < 0.05) distinguishing species, suggesting changes in energy production and metabolism in mouse cortical regions relative to human kidneys. Hundreds of potential ligand–receptor interactions were identified within glomeruli and regions of proximal tubules–peritubular capillaries, including known and novel interactions relevant to kidney physiology. Our application of ST-seq to normal human and murine kidneys confirms current knowledge and localization of transcripts within the kidney. Furthermore, the generated ST-seq datasets provide a valuable resource for the kidney community that can be used to inform future research into this complex organ.

The coronavirus disease (COVID-19) pandemic fundamentally disrupted humans’ social life and behavior. Public health measures may have inadvertently impacted how people care for each other. This study investigated prosocial behavior, its association well-being, and predictors of prosocial behavior during the first COVID-19 pandemic lockdown and sought to understand whether region-specific differences exist. Participants (N = 9,496) from eight regions clustering multiple countries around the world responded to a cross-sectional online-survey investigating the psychological consequences of the first upsurge of lockdowns in spring 2020. Prosocial behavior was reported to occur frequently. Multiple regression analyses showed that prosocial behavior was associated with better well-being consistently across regions. With regard to predictors of prosocial behavior, high levels of perceived social support were most strongly associated with prosocial behavior, followed by high levels of perceived stress, positive affect and psychological flexibility. Sociodemographic and psychosocial predictors of prosocial behavior were similar across regions.

Seasonal vaccination against influenza and in-pandemic COVID-19 vaccination are top public health priorities; vaccines are the primary means of reducing infections and also controlling pressures on health systems. During the 2018–2019 influenza season, we conducted a study of the knowledge, attitudes, and behaviours of 159 general practitioners (GPs) and 189 patients aged ≥65 years in England using a combination of qualitative and quantitative approaches to document beliefs about seasonal influenza and seasonal influenza vaccine. GPs were surveyed before and after a continuing medical education (CME) module on influenza disease and vaccination with an adjuvanted trivalent influenza vaccine (aTIV) designed for patients aged ≥65 years, and patients were surveyed before and after a routine visit with a GP who participated in the CME portion of the study. The CME course was associated with significantly increased GP confidence in their ability to address patients’ questions and concerns about influenza disease and vaccination (p < 0.001). Patients reported significantly increased confidence in the effectiveness and safety of aTIV after meeting their GP. Overall, 82.2% of the study population were vaccinated against influenza (including 137 patients vaccinated during the GP visit and 15 patients who had been previously vaccinated), a rate higher than the English national average vaccine uptake of 72.0% that season. These findings support the value of GP-patient interactions to foster vaccine acceptance.

Background Individual behaviour changes, such as hand hygiene and physical distancing, are required on a population scale to reduce transmission of infectious diseases such as COVID-19. However, little is known about effective methods of communicating risk reducing information, and how populations might respond.Objective To synthesise evidence relating to what (1) characterises effective public health messages for managing risk and preventing infectious disease and (2) influences people’s responses to messages.Design A rapid systematic review was conducted. Protocol is published on Prospero CRD42020188704.Data sources Electronic databases were searched: Ovid Medline, Ovid PsycINFO and Healthevidence.org, and grey literature (PsyarXiv, OSF Preprints) up to May 2020.Study selection All study designs that (1) evaluated public health messaging interventions targeted at adults and (2) concerned a communicable disease spread via primary route of transmission of respiratory and/or touch were included. Outcomes included preventative behaviours, perceptions/awareness and intentions. Non-English language papers were excluded.Synthesis Due to high heterogeneity studies were synthesised narratively focusing on determinants of intentions in the absence of measured adherence/preventative behaviours. Themes were developed independently by two researchers and discussed within team to reach consensus. Recommendations were translated from narrative synthesis to provide evidence-based methods in providing effective messaging.Results Sixty-eight eligible papers were identified. Characteristics of effective messaging include delivery by credible sources, community engagement, increasing awareness/knowledge, mapping to stage of epidemic/pandemic. To influence intent effectively, public health messages need to be acceptable, increase understanding/perceptions of health threat and perceived susceptibility.Discussion There are four key recommendations: (1) engage communities in development of messaging, (2) address uncertainty immediately and with transparency, (3) focus on unifying messages from sources and (4) frame messages aimed at increasing understanding, social responsibility and personal control. Embedding principles of behavioural science into public health messaging is an important step towards more effective health-risk communication during epidemics/pandemics.

Objective: Illness perceptions (IP) are important predictors of emotional and behavioral responses in many diseases. The current study aims to investigate the COVID-19-related IP throughout Europe. The specific goals are to understand the temporal development, identify predictors (within demographics and contact with COVID-19) and examine the impacts of IP on perceived stress and preventive behaviors.Methods: This was a time-series-cross-section study of 7,032 participants from 16 European countries using multilevel modeling from April to June 2020. IP were measured with the Brief Illness Perception Questionnaire. Temporal patterns were observed considering the date of participation and the date recoded to account the epidemiological evolution of each country. The outcomes considered were perceived stress and COVID-19 preventive behaviors.Results: There were significant trends, over time, for several IP, suggesting a small decrease in negativity in the perception of COVID-19 in the community. Age, gender, and education level related to some, but not all, IP. Considering the self-regulation model, perceptions consistently predicted general stress and were less consistently related to preventive behaviors. Country showed no effect in the predictive model, suggesting that national differences may have little relevance for IP, in this context.Conclusion: The present study provides a comprehensive picture of COVID-19 IP in Europe in an early stage of the pandemic. The results shed light on the process of IP formation with implications for health-related outcomes and their evolution.

Systemic lupus erythematosus (SLE) is a systemic, autoimmune disease that can involve virtually any organ of the body. Lupus nephritis (LN), the clinical manifestation of this disease in the kidney, is one of the most common and severe outcomes of SLE. Although a key pathological hallmark of LN is glomerular inflammation and damage, tubulointerstitial lesions have been recognized as an important component in the pathology of LN. Renal tubular epithelial cells are resident cells in the tubulointerstitium that have been shown to play crucial roles in various acute and chronic kidney diseases. In this context, recent progress has been made in examining the functional role of tubular epithelial cells in LN pathogenesis. This review summarizes recent advances in our understanding of renal tubular epithelial cells in LN, the potential role of tubular epithelial cells as biomarkers in the diagnosis, prognosis, and treatment of LN, and the future therapeutic potential of targeting the tubulointerstitium for the treatment of patients with LN.

Seasonal influenza can have serious morbid consequences and can even result in death, particularly in at-risk populations, including healthcare professionals (HCPs), elderly and those living with a medical risk condition. Although in Europe recommendations exist for annual influenza vaccination in these populations in most countries, the vaccination coverage rate (VCR) is often well below the World Health Organization target of 75% coverage. In our previous survey in 2009 we showed that some elements of national vaccination policies, e.g. reminder systems, strong official recommendation, and easy access, seemed to contribute to achieving higher influenza VCRs among elderly. We repeated the survey in 2016, using the same methodology to assess changes in influenza VCRs among the elderly and in the impact of policy elements on these VCRs. In addition, we collected information about VCRs among HCPs, and those living with a medical risk condition. The median VCR in the 21 countries that had recommendations for influenza vaccination in the elderly was 35.3%, ranging from 1.1% in Estonia to 74.5% in Scotland. The average VCRs for HCPs and those living with medical risk conditions, available in 17 and 10 countries, respectively, were 28.3% (range 7% in Czech Republic to 59.1% in Portugal) and 32.2% (range from 20.0% in the Czech Republic and Hungary to 59.6% in Portugal), respectively. Fewer countries were able to provide data from HCP and those living with medical risk conditions. Since the initial survey during the 2007–2008 influenza season, VCRs have decreased in the elderly in the majority of countries, thus, achieving high VCRs in the elderly and the other target groups is still a major public health challenge in Europe. This could be addressed by the identification, assessment and sharing of best practice for influenza vaccination policies.

Background: Human natural killer (NK) cells are key functional players in kidney transplant rejection. However, the respective contributions of the two functionally distinct human NK cell subsets (CD56bright cytokine-producing vs. CD56dim cytotoxic effector) in episodes of allograft rejection remain uncertain, with current immunohistochemical methods unable to differentiate these discrete populations. We report the outcomes of an innovative multi-color flow cytometric-based approach to unequivocally define and evaluate NK cell subsets in human kidney allograft rejection.Methods: We extracted renal lymphocytes from human kidney transplant biopsies. NK cell subsets were identified, enumerated, and phenotyped by multi-color flow cytometry. Dissociation supernatants were harvested and levels of soluble proteins were determined using a multiplex bead-based assay. Results were correlated with the histopathological patterns in biopsies—no rejection, borderline cellular rejection, T cell-mediated rejection (TCMR), and antibody-mediated rejection (AMR).Results: Absolute numbers of only CD56bright NK cells were significantly elevated in TCMR biopsies. In contrast, both CD56bright and CD56dim NK cell numbers were significantly increased in biopsies with histopathological evidence of AMR. Notably, expression of the activation marker CD69 was only significantly elevated on CD56dim NK cells in AMR biopsies compared with no rejection biopsies, indicative of a pathogenic phenotype for this cytotoxic NK cell subset. In line with this, we detected significantly elevated levels of cytotoxic effector molecules (perforin, granzyme A, and granulysin) in the dissociation supernatants of biopsies with a histopathological pattern of AMR.Conclusions: Our results indicate that human NK cell subsets are differentially recruited and activated during distinct types of rejection, suggestive of specialized functional roles.

Vaccine hesitancy is a complex health problem, with various factors involved including the influence of an individual’s network. According to the Social Contagion Theory, attitudes and behaviours of an individual can be contagious to others in their social networks. This scoping review aims to collate evidence on how attitudes and vaccination uptake are spread within social networks. Databases of PubMed, PsycINFO, Embase, and Scopus were searched with the full text of 24 studies being screened. A narrative synthesis approach was used to collate the evidence and interpret findings. Eleven cross-sectional studies were included. Participants held more positive vaccination attitudes and greater likelihood to get vaccinated or vaccinate their child when they were frequently exposed to positive attitudes and frequently discussing vaccinations with family and friends. We also observed that vaccination uptake was decreased when family and friends were hesitant to take the vaccine. Homophily—the tendency of similar individuals to be connected in a social network—was identified as a significant factor that drives the results, especially with respect to race and ethnicity. This review highlights the key role that social networks play in shaping attitudes and vaccination uptake. Public health authorities should tailor interventions and involve family and friends to result in greater vaccination uptake.

The success of large-scale COVID-19 vaccination campaigns is contingent upon people being willing to receive the vaccine. Our study explored COVID-19 vaccine hesitancy and its correlates in eight different countries around the globe. We analyzed convenience sample data collected between March 2020 and January 2021 as part of the iCARE cross-sectional study. Univariate and multivariate statistical analyses were conducted to explore the correlates of vaccine hesitancy. We included 32,028 participants from eight countries, and observed that 27% of the participants exhibited vaccine hesitancy, with increases over time. France reported the highest level of hesitancy (47.3%) and Brazil reported the lowest (9.6%). Women, younger individuals (≤29 years), people living in rural areas, and those with a lower perceived income were more likely to be hesitant. People who previously received an influenza vaccine were 70% less likely to report COVID-19 vaccine hesitancy. We observed that people reporting greater COVID-19 health concerns were less likely to be hesitant, whereas people with higher personal financial concerns were more likely to be hesitant. Our findings indicate that there is substantial vaccine hesitancy in several countries, with cross-national differences in the magnitude and direction of the trend. Vaccination communication initiatives should target hesitant individuals (women, younger adults, people with lower incomes and those living in rural areas), and should highlight the immediate health, social and economic benefits of vaccination across these settings. Country-level analyses are warranted to understand the complex psychological, socio-environmental, and cultural factors associated with vaccine hesitancy.

Public health teams need to understand how the public responds to vaccination messages in a pandemic or epidemic to inform successful campaigns encouraging the uptake of new vaccines as they become available. A rapid systematic review was performed by searching PsycINFO, MEDLINE, healthevidence.org, OSF Preprints and PsyArXiv Preprints in May 2020 for studies including at least one health message promoting vaccine uptake of airborne-, droplet- and fomite-spread viruses. Included studies were assessed for quality using the Mixed Methods Appraisal Tool (MMAT) or the Assessment of Multiple Systematic Reviews (AMSTAR), and for patient and public involvement (PPI) in the research. Thirty-five articles were included. Most reported messages for seasonal influenza (n = 11; 31%) or H1N1 (n = 11; 31%). Evidence from moderate to high quality studies for improving vaccine uptake included providing information about virus risks and vaccination safety, as well as addressing vaccine misunderstandings, offering vaccination reminders, including vaccination clinic details, and delivering mixed media campaigns across hospitals or communities. Behavioural influences (beliefs and intentions) were improved when: shorter, risk-reducing or relative risk framing messages were used; the benefits of vaccination to society were emphasised; and beliefs about capability and concerns among target populations (e.g., vaccine safety) were addressed. Clear, credible, messages in a language target groups can understand were associated with higher acceptability. Two studies (6%) described PPI in the research process. Future campaigns should consider the beliefs and information needs of target populations in their design, including ensuring that vaccine eligibility and availability is clear, and messages are accessible. More high quality research is needed to demonstrate the effects of messaging interventions on actual vaccine uptake.

Inflammatory immune cells play direct pathological roles in cases of acute kidney injury (AKI) and chronic kidney disease (CKD). However, the identification and characterization of distinct populations of leukocytes in human kidney biopsies have been confounded by the limitations of immunohistochemical (IHC)-based techniques used to detect them. This methodology is not amenable to the combinations of multiple markers necessary to unequivocally define discrete immune cell populations. We have developed a multi-parameter, flow cytometric-based approach that addresses the need for panels of cell-specific markers in the identification of immune cell populations, allowing both the accurate detection and quantitation of leukocyte subpopulations from a single, clinical kidney biopsy specimen. In this approach, fresh human kidney tissue is dissociated into a single cell suspension followed by antibody-labeling and flow cytometric-based acquisition and analysis. This novel technique provides a major step forward in identifying and enumerating immune cell subpopulations in human kidney disease and is a powerful platform to complement traditional histopathological examinations of clinical kidney biopsies.

Background: Patients prescribed with medication that treats mental health conditions benefit the most compared to those prescribed with other types of medication. However, they are also the most difficult to adhere. The development of mobile health (mHealth) applications (“apps”) to help patients monitor their adherence is fast growing but with limited evidence on their efficacy. There is no evidence on the content of these apps for patients taking psychotropic medication. The aim of this study is to identify and evaluate the aims and functioning of available apps that are aiming to help and educate patients to adhere to medication that treats mental health conditions.Method: Three platform descriptions (Apple, Google, and Microsoft) were searched between October 2015 and February 2016. Included apps need to focus on adherence to medication that treats mental health conditions and use at least a reinforcement strategy. Descriptive information was extracted and apps evaluated on a number of assessment criteria using content analysis.Results: Sixteen apps were identified. All apps included self-monitoring properties like reminders and psycho-educational properties like mood logs. It was unclear how the latter were used or how adherence was measured. Major barriers to medication adherence like patients' illness and medication beliefs and attitudes were not considered nor where information to patients about mediation side effects. Very few apps were tailored and none was developed based on established theories explaining the processes for successful medication adherence like cognitions and beliefs. Reported information on app development and validation was poor.Discussion: A variety of apps with different properties that tackle both intentional and unintentional non-adherence from a different perspective are identified. An evidence-based approach and co-creation with patients is needed. This will ensure that the apps increase the possibility to impact on non-adherence. Theories like social cognition models can be useful in ensuring that patients' education, motivation, skills, beliefs, and type of adherence are taken into consideration when developing the apps. Findings from this study can help clinicians and patients make informed choices and pursue policy-makers to integrate evidence when developing future apps. Quality-assurance tools are needed to ensure the apps are systematically evaluated.

The aim of this study is to explore the information needs of men with prostate cancer and their partners retrospectively at various points in the treatment process. An online questionnaire was used to collect information from men with prostate cancer and their partners about information needs, and when these developed. Readers of a Prostate Care Cookbook and members of a Prostate Cancer Charity were invited to participate: 73 men with prostate cancer and 25 partners completed the questionnaire. Responses showed that participants develop their information needs close to diagnosis. Less educated men with prostate cancer and partners developed their needs closer to the time after diagnosis than those with higher education. Partners develop an interest on information related to treatment and interaction earlier than patients. Patients prioritised treatment and disease-specific information. Patients and partners differ in how their information needs develop. Medical information is prioritized by patients as opposed to practical information by partners. Health care provision can be tailored to meet the different needs of prostate cancer patients and their partners at different times in the treatment process

Background: Approximately one out of two patients do not take their medication three months after therapy starts; while in patients with mental disorders this number varies. The WHO published a guide for clinicians, advising them to develop strategies for improving medication adherence. Aims: The aim of this project is to develop a smartphone application that will help patients adhere to their psychotropic medication and clinicians to keep track of their patients’ adherence. Methods: In Phase I we will design an application based on scientific evidence and employ software and psychological (i.e. cognitive behavioural therapy) techniques to inform the applications’ features. In Phase II we will use patient and clinical focus groups to validate in the process the applications’ usability and effectiveness. Results: We expect to develop a framework to assess the feasibility and usability of the application’s features. We also expect to have a first version of the application, which will be used in further studies using evaluation methodologies to update its content. Project is in the early stages of development. Conclusions: Implementing such an app will lead to an effective and possibly low cost method for improving psychotropic medication adherence with significant benefits for both patients and clinicians. The applications’ integration with usual care will lead to social Benefits like higher quality of care, clinical effectiveness, reduced healthcare costs and time consumption, advantages of online possibilities and better patient outcomes like quality of life and patient satisfaction with care provision. Supplementary Material: Technological aspects of the application • The user will be able to organise their medication schedule (patient user) or monitor patients’ adherence (clinician user) using their smartphone or computer. • In order to store and access information that are related to several drugs or medicines a Database Management System (DBMS) will be required. • To ensure that users have the latest information regarding existing drugs on their device, the application will access the remote database in regular time intervals to check if data stored in the user’s device have changed (or deleted) from the remote database. • Our implementation will support the communication between different smart-phone devices (client-server model). • Our implementation will be highly secure in order to protect data privacy of its users.