Tracking Salmonella-Specific CD4 T Cells In Vivo Reveals a Local Mucosal Response to a Disseminated Infection

AbstractA novel adoptive transfer system was used to track the fate of naive Salmonella-specific CD4 T cells in vivo. These cells showed signs of activation in the Peyer's patches as early as 3 hr after oral infection. The activated CD4 T cells then produced IL-2 and proliferated in the T cell areas of these tissues before migrating into the B cell-rich follicles. In contrast, Salmonella-specific CD4 T cells were not activated in the spleen and very few of these cells migrated to the liver, despite the presence of bacteria in both organs. These results show that the T cell response to pathogenic Salmonella infection is localized to the gut-associated lymphoid tissue and does not extend efficiently to the major sites of late infection

Vaccine hesitancy as an opportunity for engagement: A rapid qualitative study of patients and employees in the U.S. Veterans Affairs healthcare system.

Although COVID-19 vaccines have been available to many U.S. Veterans Affairs (VA) healthcare system employees and Veteran patients since early 2021, vaccine receipt data indicates some groups are not receiving them. Our objective was to conduct a rapid qualitative assessment of Veterans and VA employees views on COVID-19 vaccination to inform clinical leaders ongoing efforts to increase vaccine uptake across the VA. We employed semi-structured interviews and a focus group involving employees and Veterans as part of a quality improvement project between January and June 2021 at three VA medical centers. Thirty-one employees and 27 Veterans participated in semi-structured interviews; 5 Veterans from a national stakeholder organization participated in a focus group. Data were analyzed using directed content analysis, involving an a priori coding framework comprised of four domains with subcodes under each: contextual influences, barriers and facilitators, vaccine-specific issues, and VA/military experiences. We then classified initial codes into five categories of hesitancy: vaccine deliberation, dissent, distrust, indifference and skepticism. A subset of Veterans (n = 14) and employees (n = 8) identified as vaccine hesitant. Vaccine hesitancy categories were represented by subcodes of religion, culture, gender or socio-economic factors, perceptions of politics and policies, role of healthcare providers, and historical influences; (contextual influences); knowledge or awareness of vaccines, perceived susceptibility to COVID-19, and beliefs and attitudes about health and illness (barriers and facilitators); vaccine development process (vaccine-specific issues) and military experiences (VA/military factors). Facilitators involved talking with trusted others, ease of vaccine access, and perceptions of family and societal benefits of vaccines. Vaccine hesitancy is multi-faceted and likely requires multiple strategies for engaging in conversations to address Veteran and VA employee concerns. Messages should involve patient-centered communication strategies delivered by trusted healthcare providers and peers and should focus on addressing expected benefits for family, friends, and society

First Is Best

We experience the world serially rather than simultaneously. A century of research on human and nonhuman animals has suggested that the first experience in a series of two or more is cognitively privileged. We report three experiments designed to test the effect of first position on implicit preference and choice using targets that range from individual humans and social groups to consumer goods. Experiment 1 demonstrated an implicit preference to buy goods from the first salesperson encountered and to join teams encountered first, even when the difference in encounter is mere seconds. In Experiment 2 the first of two consumer items presented in quick succession was more likely to be chosen. In Experiment 3 an alternative hypothesis that first position merely accentuates the valence of options was ruled out by demonstrating that first position enhances preference for the first even when it is evaluatively negative in meaning (a criminal). Together, these experiments demonstrate a “first is best” effect and we offer possible interpretations based on evolutionary mechanisms of this “bound” on rational behavior and suggest that automaticity of judgment may be a helpful principle in clarifying previous inconsistencies in the empirical record on the effects of order on preference and choice

The limitations of employment as a tool for social inclusion

<p>Abstract</p> <p>Background</p> <p>One important component of social inclusion is the improvement of well-being through encouraging participation in employment and work life. However, the ways that employment contributes to wellbeing are complex. This study investigates how poor health status might act as a barrier to gaining good quality work, and how good quality work is an important pre-requisite for positive health outcomes.</p> <p>Methods</p> <p>This study uses data from the PATH Through Life Project, analysing baseline and follow-up data on employment status, psychosocial job quality, and mental and physical health status from 4261 people in the Canberra and Queanbeyan region of south-eastern Australia. Longitudinal analyses conducted across the two time points investigated patterns of change in employment circumstances and associated changes in physical and mental health status.</p> <p>Results</p> <p>Those who were unemployed and those in poor quality jobs (characterised by insecurity, low marketability and job strain) were more likely to remain in these circumstances than to move to better working conditions. Poor quality jobs were associated with poorer physical and mental health status than better quality work, with the health of those in the poorest quality jobs comparable to that of the unemployed. For those who were unemployed at baseline, pre-existing health status predicted employment transition. Those respondents who moved from unemployment into poor quality work experienced an increase in depressive symptoms compared to those who moved into good quality work.</p> <p>Conclusions</p> <p>This evidence underlines the difficulty of moving from unemployment into good quality work and highlights the need for social inclusion policies to consider people's pre-existing health conditions and promote job quality.</p

Rationale and protocol for a cluster randomized pragmatic clinical trial testing behavioral economic implementation strategies to improve tobacco treatment rates for cancer patients who smoke

Background Routine evidence-based tobacco use treatment minimizes cancer-specific and all-cause mortality, reduces treatment-related toxicity, and improves quality of life among patients receiving cancer care. Few cancer centers employ mechanisms to systematically refer patients to evidence-based tobacco cessation services. Implementation strategies informed by behavioral economics can increase tobacco use treatment engagement within oncology care. Methods A four-arm cluster-randomized pragmatic trial will be conducted across nine clinical sites within the Implementation Science Center in Cancer Control Implementation Lab to compare the effect of behavioral economic implementation strategies delivered through embedded messages (or “nudges”) promoting patient engagement with the Tobacco Use Treatment Service (TUTS). Nudges are electronic medical record (EMR)-based messages delivered to patients, clinicians, or both, designed to counteract known patient and clinician biases that reduce treatment engagement. We used rapid cycle approaches (RCA) informed by relevant stakeholder experiences to refine and optimize our implementation strategies and methods prior to trial initiation. Data will be obtained via the EMR, clinician survey, and semi-structured interviews with a subset of clinicians and patients. The primary measure of implementation is penetration, defined as the TUTS referral rate. Secondary outcome measures of implementation include patient treatment engagement (defined as the number of patients who receive FDA-approved medication or behavioral counseling), quit attempts, and abstinence rates. The semi-structured interviews, guided by the Consolidated Framework for Implementation Research, will assess contextual factors and patient and clinician experiences with the nudges. Discussion This study will be the first in the oncology setting to compare the effectiveness of nudges to clinicians and patients, both head-to-head and in combination, as implementation strategies to improve TUTS referral and engagement. We expect the study to (1) yield insights into the effectiveness of nudges as an implementation strategy to improve uptake of evidence-based tobacco use treatment within cancer care, and (2) advance our understanding of the multilevel contextual factors that drive response to these strategies. These results will lay the foundation for how patients with cancer who smoke are best engaged in tobacco use treatment and may lead to future research focused on scaling this approach across diverse centers. Trial registration Clinicaltrials.gov, NCT04737031 . Registered 3 February 2021

Reasons for non-recruitment of eligible patients to a randomised controlled trial of secondary prevention after intracerebral haemorrhage: observational study.

Recruitment to randomised prevention trials is challenging, not least for intracerebral haemorrhage (ICH) associated with antithrombotic drug use. We investigated reasons for not recruiting apparently eligible patients at hospital sites that keep screening logs in the ongoing REstart or STop Antithrombotics Randomised Trial (RESTART), which seeks to determine whether to start antiplatelet drugs after ICH.EDGE project number 14013British Heart Foundation Special Project (SP/12/2/29422) & Project (PG/14/50/30891) fundin

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

In the eye of the storm : should I stay or should I go? Reflections on the middle phase of a problem-based learning group

Original article can be found at : http://www.tandfonline.com/ Copyright Taylor & FrancisThis paper reports on the middle phase of a problem-based learning (PBL) group undergoing clinical psychology training at the University of Hertfordshire (UH). Trainers and trainees involved in PBL at UH provide some personal reflections on their experiences, highlighting some of the unique characteristics and dilemmas of participating in this middle phase of PBL. We explore themes around the dynamics within the group, the emotional experiences evoked for participants, and some of the strategies used to manage these emotions. We conclude with implications of this type of learning for clinical training.Peer reviewedFinal Accepted Versio