A scoping review: virtual patients for communication skills in medical undergraduates.

BACKGROUND: Communication is an essential competence for medical students. Virtual patients (VP), computerized educational tools where users take the role of doctor, are increasingly used. Despite the wide range of VP utilization, evidence-based practical guidance on supporting development of communication skills for medical students remains unclear. We focused this scoping review on VP affordance for student learning especially important in the current environment of constrained patient access. METHODS: This scoping review followed Arksey & O'Malley's methodology. We tested and used a search strategy involving six databases, resulting in 5,262 citations. Two reviewers independently screened titles, full texts (n= 158) and finally performed data extraction on fifty-five included articles. To support consideration of educational affordance the authors employed a pragmatic framework (derived from activity theory) to map included studies on VP structure, curricular alignment, mediation of VP activity, and socio-cultural context. RESULTS: Findings suggest that not only the VP itself, but also its contextualization and associated curricular activities influence outcomes. The VP was trialled in the highest proportion of papers as a one-off intervention (19 studies), for an average duration of 44.9 minutes (range 10-120min), mainly in senior medical students (n=23), notably the largest group of studies did not have VP activities with explicit curricular integration (47%). There was relatively little repeated practice, low levels of feedback, self-reflection, and assessment. Students viewed VPs overall, citing authenticity and ease of use as important features. Resource implications are often omitted, and costings would facilitate a more complete understanding of implications of VP use. CONCLUSION: Students should be provided with maximal opportunity to draw out the VPs' full potential through repeated practice, without time-constraint and with curricular alignment. Feedback delivery enabling reflection and mastery is also key. The authors recommend educators to explicitly balance computerized authenticity with instructional design integrated within the curriculum.

Self-regulatory learning theory as a lens on how undergraduate and postgraduate learners respond to feedback: A BEME scoping review: BEME Guide No. 66.

INTRODUCTION: Little is known of processes by which feedback affects learners to influence achievement. This review maps what is known of how learners interact with feedback, to better understand how feedback affects learning strategies, and to explore enhancing and inhibiting factors. METHODS: Pilot searching indicated a wide range of interpretations of feedback and study designs, prompting the use of scoping methodology. Inclusion criteria comprised: (i) learners (undergraduate, postgraduate, continuing education) who regularly receive feedback, and (ii) studies that associated feedback with subsequent learner reaction. The screening was performed independently in duplicate. Data extraction and synthesis occurred via an iterative consensus approach. Self-regulatory learning theory (SRL) was used as the conceptual framework. RESULTS: Of 4253 abstracts reviewed, 232 were included in the final synthesis. Understandings of feedback are diverse; a minority adopt recognised definitions. Distinct learner responses to feedback can be categorized as cognitive, behavioural, affective, and contextual with complex, overlapping interactions. Importantly emotional responses are commonplace; factors mediating them are pivotal in learner recipience. CONCLUSION: Feedback benefits learners most when focussed on learner needs, via engagement in bi-directional dialogue. Learner emotions must be supported, with the construction of positive learner-teacher relationships. A developmental agenda is key to learner's acceptance of feedback and enhancing future learning.

The 'connectaholic' behind the curtain: medical student use of computer devices in the clinical setting and the influence of patients.

BACKGROUND: The use of mobile devices such as tablets and laptops by students to support their learning is now ubiquitous. The clinical setting is an environment, which lends itself to the use of mobile devices as students are exposed to novel clinical scenarios that may require rapid location of information to address knowledge gaps. It is unknown what preferences students have for these devices and how they are used in the clinical environment. METHODS: In this study we explored medical students' choices and their use of different devices in their first year of clinical attachments. We sought to evaluate learners' experiences with these devices using a mixed methods approach. All students newly entered into the clinical years were given the option of a MacBook Air or iPad. We surveyed these students using an online survey tool followed by individual semi-structured interviews to explore survey findings in more depth. RESULTS: Students owned a multitude of devices however their preferences were for the 11 in. MacBook Air Laptop over the iPad mini. Students made constant use of online information to support their clinical learning, however three major themes emerged from the interview data: connection and devices (diverse personal ownership of technology by students and how this is applied to source educational materials), influence and interaction with patients (use of any device in a clinical setting) and influence and interaction with staff. In general students preferred to use their device in the absence of patients however context had a significant influence. CONCLUSIONS: These mobile devices were useful in the clinical setting by allowing access to online educational material. However, the presence of patients, and the behaviour of senior teaching staff significantly influenced their utilisation by students. Understanding the preferences of students for devices and how they use their preferred devices can help inform educational policy and maximise the learning from online educational content.

Pharmacological impact of antiretroviral therapy on platelet function to investigate human immunodeficiency virus-associated cardiovascular risk.

BACKGROUND AND PURPOSE: Some clinical studies have reported increased myocardial infarction in people living with human immunodeficiency virus (HIV) taking the antiretroviral abacavir sulphate (ABC). Given that clinical studies contain confounding variables (e.g., HIV-associated factors), we investigated the pharmacological effects of antiretrovirals on platelet function in HIV-negative volunteers in order to identify mechanisms of increased cardiovascular risk. EXPERIMENTAL APPROACH: Platelets were isolated from healthy volunteers and HIV-negative subjects enrolled on a Phase I clinical trial and platelet function evaluated using aggregometry and flow cytometry. In vivo platelet thromboembolism was monitored in anaesthetized mice. KEY RESULTS: Human platelet aggregation was unaffected by all antiretrovirals tested, but ABC treatment led uniquely to increased platelet granule release. ABC also interrupted NO-mediated inhibition of platelet aggregation and increased in vivo aggregation in mice. Another antiretroviral, tenofovir, did not affect platelet function. Furthermore, aggregation and activation of platelets isolated from 20 subjects taking clinically relevant doses of tenofovir were comparable to baseline samples. CONCLUSIONS AND IMPLICATIONS: ABC can enhance platelet activation, independently of variables that confound clinical studies, suggesting a potential pharmacological effect that is absent with tenofovir. Mechanistically, we propose that ABC enhances platelet degranulation and interrupts NO-mediated platelet inhibition. The interaction of ABC with NO signalling is demonstrated by ABC-mediated enhancement of aggregation in vivo and in vitro that persisted in the presence of NO. Although an association between ABC and platelet activation has not been confirmed in patients, these findings provide evidence of a mechanistic link between platelet activation and antiretroviral therapy.

Translocator Protein as an Imaging Marker of Macrophage and Stromal Activation in Rheumatoid Arthritis Pannus.

PET radioligands targeted to translocator protein (TSPO) offer a highly sensitive and specific means of imaging joint inflammation in rheumatoid arthritis (RA). Through high expression of TSPO on activated macrophages, TSPO PET has been widely reported in several studies of RA as a means of imaging synovial macrophages in vivo. However, this premise does not take into account the ubiquitous expression of TSPO. This study aimed to investigate TSPO expression in major cellular constituents of RA pannus-monocytes, macrophages, fibroblastlike synoviocytes (FLS cells), and CD4-positive (CD4+) T lymphocytes (T cells)-to more accurately interpret TSPO PET signal from RA synovium. Methods: Three RA patients and 3 healthy volunteers underwent PET of both knees using the TSPO radioligand 11C-PBR28. Through 3H-PBR28 autoradiography and immunostaining of synovial tissue in 6 RA patients and 6 healthy volunteers, cellular expression of TSPO in synovial tissue was evaluated. TSPO messenger RNA expression and 3H-PBR28 radioligand binding was assessed using in vitro monocytes, macrophages, FLS cells, and CD4+ T cells. Results:11C-PBR28 PET signal was significantly higher in RA joints than in healthy joints (average SUV, 0.82 ± 0.12 vs. 0.03 ± 0.004; P < 0.01). Further, 3H-PBR28-specific binding in synovial tissue was approximately 10-fold higher in RA patients than in healthy controls. Immunofluorescence revealed TSPO expression on macrophages, FLS cells, and CD4+ T cells. The in vitro study demonstrated the highest TSPO messenger RNA expression and 3H-PBR28-specific binding in activated FLS cells, nonactivated M0 macrophages, and activated M2 reparative macrophages, with the least TSPO expression being in activated and nonactivated CD4+ T cells. Conclusion: To our knowledge, this study was the first evaluation of cellular TSPO expression in synovium, with the highest TSPO expression and PBR28 binding being found on activated synovial FLS cells and M2 macrophages. TSPO-targeted PET may therefore have a unique sensitivity in detecting FLS cells and macrophage-predominant inflammation in RA, with potential utility for assessing treatment response in trials using novel FLS-cell-targeted therapies.

Refinement of Mouse Protocols for the Study of Platelet Thromboembolic Responses In Vivo.

Mouse models of thromboembolism are frequently used to investigate platelet function in vivo and, according to European Union (EU) legislation, must be conducted in the context of replacement, refinement and reduction. We have previously developed a refined real-time mouse model of thromboembolism as an alternative to models of thromboembolic mortality which inflict considerable pain and suffering. Real-time monitoring involves infusion of radiolabelled platelets into the circulation of anaesthetized mice, and platelet aggregation is measured as increases in platelet-associated counts in the pulmonary vasculature following injection of platelet agonists. This gives a definitive data set on the tissue localization and extent of platelet activation. We developed an additional, more simplistic alternative to mortality models based on blood microsampling which entails the measurement of circulating platelet counts following agonist stimulation. Blood microsamples were collected from the tail vein of anaesthetized mice at three different time points leading to a reduction in animal numbers. Platelet counts significantly dropped 1 minute after stimulation with collagen or thrombin and were restored over 10 minutes. These results correlate with those obtained via real-time monitoring and were confirmed by immunohistochemistry. Pre-treatment of mice with aspirin significantly inhibited the decrease in platelet counts following collagen. These data suggest that blood microsampling may be implemented as a simplistic refined alternative to mortality models of thromboembolism when specialized monitoring equipment, or use of radioactive isotopes for real-time monitoring, which remains the 'gold standard', is not feasible. Microsampling refines and reduces animal procedures in compliance with current EU legislation.

The macrophage marker translocator protein (TSPO) is down-regulated on pro-inflammatory 'M1' human macrophages.

The translocator protein (TSPO) is a mitochondrial membrane protein, of as yet uncertain function. Its purported high expression on activated macrophages, has lent utility to TSPO targeted molecular imaging in the form of positron emission tomography (PET), as a means to detect and quantify inflammation in vivo. However, existing literature regarding TSPO expression on human activated macrophages is lacking, mostly deriving from brain tissue studies, including studies of brain malignancy, and inflammatory diseases such as multiple sclerosis. Here, we utilized three human sources of monocyte derived macrophages (MDM), from THP-1 monocytes, healthy peripheral blood monocytes and synovial fluid monocytes from patients with rheumatoid arthritis, to undertake a detailed investigation of TSPO expression in activated macrophages. In this work, we demonstrate a consistent down-regulation of TSPO mRNA and protein in macrophages activated to a pro-inflammatory, or 'M1' phenotype. Conversely, stimulation of macrophages to an M2 phenotype with IL-4, dexamethasone or TGF-ß1 did not alter TSPO expression, regardless of MDM source. The reasons for this are uncertain, but our study findings add some supporting evidence for recent investigations concluding that TSPO may be involved in negative regulation of inflammatory responses in macrophages.

Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans.

The 18kDa Translocator Protein (TSPO) is the most commonly used tissue-specific marker of inflammation in positron emission tomography (PET) studies. It is expressed in myeloid cells such as microglia and macrophages, and in rodent myeloid cells expression increases with cellular activation. We assessed the effect of myeloid cell activation on TSPO gene expression in both primary human and rodent microglia and macrophages in vitro, and also measured TSPO radioligand binding with 3H-PBR28 in primary human macrophages. As observed previously, we found that TSPO expression increases (∼9-fold) in rodent-derived macrophages and microglia upon pro-inflammatory stimulation. However, TSPO expression does not increase with classical pro-inflammatory activation in primary human microglia (fold change 0.85 [95% CI 0.58-1.12], p = 0.47). In contrast, pro-inflammatory activation of human monocyte-derived macrophages is associated with a reduction of both TSPO gene expression (fold change 0.60 [95% CI 0.45-0.74], p = 0.02) and TSPO binding site abundance (fold change 0.61 [95% CI 0.49-0.73], p < 0.0001). These findings have important implications for understanding the biology of TSPO in activated macrophages and microglia in humans. They are also clinically relevant for the interpretation of PET studies using TSPO targeting radioligands, as they suggest changes in TSPO expression may reflect microglial and macrophage density rather than activation phenotype.

Induction and enhancement of platelet aggregation in vitro and in vivo by model polystyrene nanoparticles.

Nanoparticles (NPs) may come into contact with circulating blood elements including platelets following inhalation and translocation from the airways to the bloodstream or during proposed medical applications. Studies with model polystyrene latex nanoparticles (PLNPs) have shown that NPs are able to induce platelet aggregation in vitro suggesting a poorly defined potential mechanism of increased cardiovascular risk upon NP exposure. We aimed to provide insight into the mechanisms by which NPs may increase cardiovascular risk by determining the impact of a range of concentrations of PLNPs on platelet activation in vitro and in vivo and identifying the signaling events driving NP-induced aggregation. Model PLNPs of varying nano-size (50 and 100 nm) and surface chemistry [unmodified (uPLNP), amine-modified (aPLNP) and carboxyl-modified (cPLNP)] were therefore examined using in vitro platelet aggregometry and an established mouse model of platelet thromboembolism. Most PLNPs tested induced GPIIb/IIIa-mediated platelet aggregation with potencies that varied with both surface chemistry and nano-size. Aggregation was associated with signaling events, such as granule secretion and release of secondary agonists, indicative of conventional agonist-mediated aggregation. Platelet aggregation was associated with the physical interaction of PLNPs with the platelet membrane or internalization. 50 nm aPLNPs acted through a distinct mechanism involving the physical bridging of adjacent non-activated platelets leading to enhanced agonist-induced aggregation in vitro and in vivo. Our study suggests that should they translocate the pulmonary epithelium, or be introduced into the blood, NPs may increase the risk of platelet-driven events by inducing or enhancing platelet aggregation via mechanisms that are determined by their distinct combination of nano-size and surface chemistry.