The visual pathway provides a unique opportunity for in vivo assessment of myelin damage and repair in the MS-affected brain since it is highly susceptible to damage in MS and is a very frequent site of MS lesions. The visually evoked potential (VEP), an event-related potential generated by the striate cortex in response to visual stimulation, is uniquely placed to serve as a biomarker of the myelination along the visual pathway. The multifocal VEP (mfVEP) represents a most recent addition to the array of VEP stimulations. This article provides a current view on the role of mfVEP as a biomarker of demyelination, spontaneous remyelination, and myelin repair in MS.Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS), characterized by inflammation, demyelination, neuro-axonal loss, and gliosis. Inflammatory demyelinating lesions are a hallmark of the disease. Spontaneous remyelination, however, is often incomplete and strategies that promote remyelination are needed. As a result, accurate and sensitive  Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS), characterized by inflammation, demyelination, neuro-axonal loss, and gliosis. Inflammatory demyelinating lesions are a hallmark of the disease. The acute stage of lesion formation initially results in a complete block of conduction  along the axons affected by the inflammation. Axonal conduction (and function), however, typically recovers within a few weeks, during which inflammation subsides, ion channels are reconstructed and conduction in surviving but demyelinated axons resumes, although often in a slower, continuous mode . This re2+-mediated axonal degeneration  is the presenting symptom of MS in approximately 20% of MS patients and evidence of previous ON is typically detected in half of the relapsing-remitting (RR) MS population, while optic radiation (OR) lesions are seen in about two-thirds ], the entire length of the visual pathway, including the OR, can now be visualized and its structural damage can be quantified .In addition, contrary to many other white matter pathways, the visual pathway allows study of the dynamics of myelin alteration in both acute and chronic lesions. This is due to the fact that, while OR lesions are typically silent, lesions of the anterior visual pathway are clinically apparent.Furthermore, accurate and quantifiable measures of visual system function, such as visual acuity [and low contrast visual acuity (LCVA) in particular], are readily available .Finally, the visually evoked potential (VEP), an event-related potential generated by the striate cortex in response to visual stimulation , is uniqThis close association between VEP latency delay and degree of visual pathway demyelination has been confirmed by clinical and experimental studies. For example, Since the VEP is generated at the level of striate cortex, it is affected by pathological changes along the entire visual pathway. Therefore, latency delay of the VEP reflects the combined effect of demyelination in the entire visual system including optic nerve and OR. However, due to the unique topographic anatomy of the visual system , the effect of optic nerve and OR demyelination on VEP can be differentiated. Thus, demyelinating lesions of OR typically produce a similar delay of the VEP response in both eyes. Conversely, since lesions of the optic nerve in MS are, as a rule, unilateral, optic nerve demyelination only affects VEP recorded in response to stimulation of the affected eye. Furthermore, the monocular nature of ON allows comparison of VEP parameters recorded from the affected eye with data obtained from the fellow (unaffected) eye. Using this inter-eye latency difference (asymmetry) significantly reduces between-subject variability, providing a very accurate measure of optic nerve de/remyelination .There are several stimulating modalities that are employed to generate the VEP. Flash stimuli are typically used in animal studies and to record VEP response from non-cooperative patients or young children, while pattern-reversal full or half-field VEPs are commonly used in adults . The mulThere are several advantages of mfVEP over full-field stimulation .The conventional full-field VEP provides a summed response of all neuronal elements stimulated and is greatly dominated by the macular region due to its cortical overrepresentation . It has In addition, being the vector sum of numerous differently oriented dipoles , the waveform of the full-field VEP is prone to unpredictable change depending on the part of the nerve/visual field affected, leading sometimes to detection of apparent rather than real amplitude and latency change . This isIn contrast, the mfVEP simultaneously stimulates numerous small areas  of the visual field using pseudorandom sequences and is able to extract individual responses from each stimulated area independently and at the same time . This, tFurthermore, stimulation of small areas of the visual field eliminates the cancelation effect of various dipole orientation caused by the opposite position of upper and lower banks of calcarine sulcus (subserving the upper and lower hemifields) and cortical convolution, which is a serious limitation for the full-field VEP.Since it was established that signals derived from the peripheral areas of the visual fields are less delayed and recover faster than responses derived from the central areas of the visual fields, this may also contribute to cancelation or distortion of the full-field VEP as it is a summed response .There are various ways to measure mfVEP latency. Individual segments can be assessed independently and a retinotopically organized plot of latency delay can be constructed  .Alternatively, an averaged value of latency across all areas of the stimulated eye can be used. However, contrary to full-field VEP, averaging of mfVEP areas does not result in cancelation or distortion of the total signal since numerical values of latency not waveforms are averaged.In summary, the mfVEP better reflects the true state of the conductivity along the visual pathway by including information from fibers subserving more peripheral parts of the visual field and eliminating cancelation effects of differently oriented dipoles. Simultaneous recording from a plurality of visual field locations and use of orthogonal channels also results in higher spatial resolution of the mf VEP technique, allowing independent assessment of multiple regions.While a number of imaging techniques such as magnetization transfer ratio, diffusion tensor imaging, and myelin water fraction have been recently suggested as potential biomarkers for de/remyelination in MS lesions , there iThe majority of new white matter lesions in MS are clinically silent and, as a result, are typically detected during routine MRI examination long after the acute inflammatory stage. Optic nerve lesions, on the other hand, are usually clinically apparent from the onset and, therefore, provide a unique platform to study spontaneous remyelination, as well as treatment-induced myelin repair in the early post-acute period using VEP latency as a biomarker .Furthermore, since precise timing of ON onset is known, the ON model also offers an opportunity to investigate the effect of the lesion’s age on remyelinating capacity of any potential treating agent by studying patients with different post-ON intervals.This is of particular importance since it is believed that remyelination is more likely to succeed in the acute or recent MS lesion, while the environment for successful remyelination may become less permissive in longstanding lesions . The “wiBoth experimental and clinical studies have demonstrated that after a brief block of conduction caused by acute inflammation, the surviving, but chronically demyelinated axons largely recover the ability to conduct . This geSubsequent shortening of mfVEP latency, which is frequently observed after this initial delay, is thought to represent the process of spontaneous remyelination . The mfVIn addition, it was demonstrated that, at least in the optic nerve, the magnitude of post-acute latency shortening  is largely independent of initial latency delay . For example, while in some cases initial (4 weeks after ON onset) latency delay of the mfVEP exceeds 35–40 ms , latency improvement does not usually go beyond 10–15 ms (average latency recovery 11.3 ± 3 ms) , indicatThe acute ON model is becoming a method of choice for clinical trials aimed at myelin repair .The mfVEP has recently been used to study remyelination in a clinical trial of monoclonal antibody opicinumab, which previously shows remyelinating activity in pre-clinical studies (RENEW and RENEWED). In the RENEW study, patients were treated with 100 mg/kg opicinumab for 20 weeks and assessed up to week 32, while the RENEWED study was designed as a follow-up study at 2 years after the last visit of RENEW study.post hoc comparison of estimated effect size for change in mfVEP and full-field VEP latency for opicinumab versus placebo at week 24 in the intention-to-treat population, which showed that the mfVEP demonstrated a larger treatment effect size than full-field VEP  and the mfVEP latency demonstrated a larger improvement in ON eyes of patients treated with opicinumab compared to placebo , althougield VEP .Furthermore, while the high variability of full-field VEP precluded any meaningful assessment of amplitude, analysis of mfVEP demonstrated evidence that fellow eye amplitude loss occurs after ON but can potentially be prevented by opicinumab treatment .The RENEWED study also demonstrated higher sensitivity of mfVEP in monitoring treatment-induced remyelination compared to full-field VEP. The average difference between latency recovery of mfVEP in the treated vs. placebo group increased from 14.4 to 19.6 ms over the 2 years after treatment was terminated, while full-field VEP demonstrated reduction of latency recovery from 9.4 to 6.0 ms during the same period .r2 = 0.72, p = 0.004, Pearson correlation coefficient). Conversely, the magnitude of mfVEP latency recovery was limited in the placebo group and did not correlate with initial degree of latency delay (p = 0.2)  and the latency recovery at RENEWED day 1 (p = 0.2) , which wp = 0.2) .Therefore, in the presumed treatment-induced (opicinumab) remyelination following acute ON, the degree of myelin recovery was highly proportional to the extent of initial myelin loss .It must be noted that while the degree of acute demyelination cannot often be assessed because of frequent incidence of edema and conduction block, continuous conduction along the demyelinated part of the affected axons typically resumes by 3–4 weeks, which still provides a good indication of the extent of original demyelination .While the clinical potential for remyelination of chronic lesions is more challenging (see discussion related to “window of opportunity” above), it is also extremely important since the diagnosis of MS is typically delayed  due to tThe visual system can also be used to monitor myelin alteration in chronic lesions. As stated above, since mfVEP is generated at the level of primary (striate) visual cortex but reflects the integrity of the full visual pathway, it is affected by the speed of conduction and, therefore, degree of de/remyelination along the entire pathway, including optic nerve and OR. Accordingly, delay of mfVEP latency in non-acute ON patients does reflect the combined effect of chronic demyelination in both optic nerve and OR. Since the effect of a chronic optic nerve lesion on mfVEP is usually monocular, while OR lesions will yield binocular latency delay due to partial chiasmal crossing of visual pathway, this provides a point of differentiation.Quantitative investigation of the association between mfVEP latency delay and MS-related damage of posterior visual pathway was aided by the relatively recent development of diffusion-based tractography, which enabled identification and segmentation of major white matter tracts including ORs . InterseThe mfVEP has also recently been employed as a biomarker for clinical trials to examine possible remyelination in chronic lesions, in combination with MRI. The utility of the mfVEP is further strengthened by our longitudinal analysis, which demonstrated the remarkably stable nature of mfVEP latency after 12 months in the absence of new lesional activity in the visual pathway .While patient recruitment within a short window after symptom onset represents a limiting factor for acute ON trials, selection of patients for remyelinating trials based on chronic visual pathway lesions is less challenging. The main enrollment criteria for such trials are the presence of measurable mfVEP signal (includes ∼95% of RRMS population) and significant latency delay indicating chronic demyelination along the visual pathway (includes ∼70% of RRMS population). Furthermore, the sample size calculated for 12 months in a clinical trial of a potential remyelinating agent based on latency of the mfVEP revealed that a relatively small sample size would be required to demonstrate efficacy of remyelination therapy . This apWhile mfVEP has also been used in monitoring other neurological conditions, such as neurofibromatosis, Leber’s optic neuropathy, chronic inflammatory demyelinating polyneuropathy, optic disc drusen, chiasmal decompression, compressive optic neuropathy, and schizophrenia , its appBoth authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The volume of published academic research is growing rapidly and this new era of “big literature” poses new challenges to evidence synthesis, pushing traditional, manual methods of evidence synthesis to their limits. New technology developments, including machine learning, are likely to provide solutions to the problem of information overload and allow scaling of systematic maps to large and even vast literatures. In this paper, we outline how systematic maps lend themselves well to automation and computer‐assistance. We believe that it is a major priority to consolidate efforts to develop and validate efficient, rigorous and robust applications of these novel technologies, ensuring the challenges of big literature do not prevent the future production of systematic maps. Systematic maps typically extract only meta‐data (descriptive information about the studies and their systems) and apply predefined codes: they do not extract findings from the included studies. Systematic maps may include critical appraisal of included study validity, but this step is optional and would be conducted in full in subsequent systematic reviews. Synthesis in systematic maps involves a description of the evidence base and development of an interactive database of studies, and therefore does not include the quantitative or qualitative synthesis of study findings.Outputs: The key outputs of a systematic map are: (a) an interactive, searchable database of relevant studies and their descriptive information; (b) a list of knowledge gaps (topics where primary research is limited or absent) and knowledge clusters (topics where sufficient research exists to warrant full synthesis via systematic reviews); (c) visualisations of the evidence base to facilitate understanding ; (d) a summary report describing the background, methods and results.Terminology: The term “systematic map” is widely used in environmental science and social science. Some fields refer to this method as “evidence maps”, although this is perhaps a broader definition, procedurally. In the field of social welfare, the Campbell Collaboration has developed the term “evidence and gap map” to describe a form of evidence map that focuses on identifying systematic reviews  on a topic, and developing a matrix of interventions and outcomes to visually represent the evidence base. In the field of health, an analogous approach would be described as a “scoping review”, but this term includes a broader set of methods that include reviews conducted to a lower standard than systematic maps . https://doi.org/10.1186/s13750-016-0059-6James, K. L., Randall, N. P. & Haddaway, N. R. A methodology for systematic mapping in environmental sciences. Ambio45, 613–620 (2016). https://doi.org/10.1007/s13280-016-0773-xHaddaway, N. R., Bernes, C., Jonsson, B. et al. The benefits of systematic mapping to evidence‐based environmental management. Toxicological Sciences175, 35–49 (2020). https://doi.org/10.1093/toxsci/kfaa025Wolffe, T. A. M., Vidler, J., Halsall, C., Hunt, N., Whaley, P., A survey of systematic evidence mapping practice and the case for knowledge graphs in environmental health and toxicology, Nature News, 528, 185 (2015). https://doi.org/10.1038/528185aMcKinnon, M. C., Cheng, S. H., Garside, R., Masuda, Y. J., Miller, D. C., Sustainability: Map the evidence. Campbell Systematic Reviews, 14, 1–38 (2018). https://doi.org/10.4073/cmdp.2018.2Saran, A., White, H., Evidence and gap maps: a comparison of different approaches. We focus here on systematic mapping for two reasons  to a series of focused answers to targeted questions about impacts and “what works” , knowledge clusters  and best‐practices and/or deficiencies in research methods. They can thus help to direct impactful and needs‐driven research and funding towards primary and secondary gaps in the evidence.Systematic maps can be upgraded into full systematic reviews relatively quickly for given knowledge clusters and, in these cases, can be particularly resource efficient. They can thus be used to determine for which subtopics systematic reviews are most appropriate and feasible, reducing the risks of undesirable empty reviews.Representativeness is arguably more important than comprehensiveness in systematic maps, since the aim is to identify patterns in gaps and clusters rather than generate precise estimates: as an analogy, a photograph of the Mona Lisa is recognisable at low resolution, but it could not be considered an accurate representation of the underlying information in the painting Figure . This re3There are many key points in the traditional view of systematic mapping processes where evidence synthesis technology and computational methods could be applied, broadly speaking, project management, retrieval, screening, data extraction and narrative synthesis. We discuss these processes in the following sections.3.1and systematic map, where previously evidence synthesis would have had to be either timely or systematic. In addition, because computer‐assisted systematic maps can be continually updated to include relevant research as and when it is made available, maps can be kept up to date with the latest evidence.The computer‐assisted (or automated) systematic mapping that we describe herein has a suite of benefits to researchers, policymakers and practitioners. More rapid mapping of the evidence will result in faster synthesis in general (including the transition from systematic maps to systematic reviews), by facilitating the identification and analysis of the nature of an evidence base. In turn, this will allow evidence synthesis to be more responsive to the knowledge needs of decision‐makers. Where decision‐makers require urgent evidence on a subject, computer‐assisted mapping can make the provision of a timely 3.2evidence synthesis technologies (defined here as novel tools and frameworks used to support evidence syntheses) that currently exist and can already be used to increase the efficiency, rigour and accessibility of evidence synthesis. We explain these across the main processes of systematic mapping.1.Project management—In its broadest form, review management tools are evidence synthesis technologies that suit themselves well to systematic maps, since they support an entire flow of information through the review process, can deal with big data review projects, and facilitate good record keeping, which is vital with such large evidence bases.2.Retrieval—Text analysis processes can suggest search terms to support search string development based on computer‐assisted scoping of the literature  can begin sooner  synthesis—Visualisation of systematic map databases using cartographic/conceptual mapping tools can be used to understand the content and spread of studies of geographical/conceptual space .In healthcare, technology is being harnessed to automate several steps in the evidence synthesis process, collating, summarising and appraising all randomised control trials  bibliographic datasets could be developed and curated with supplementary information related to their contents and relation to the rest of the evidence base, for example, across broad conceptual topics such as climate change. Such open datasets would facilitate digestibility by automated processes and sharing of information across reviews that would otherwise be unnecessarily replicated. Bulk downloading should be a priority to reduce reviewer workloads and potential errors. For example, Lens.org is a free‐to‐use bibliographic database that aggregates across Microsoft Academic, CORE, CrossRef and PubMed, cataloguing >220 m academic records. It allows bulk exporting of up to 50,000 records in one go.2.Machine readable, accessible full texts—Text analysis techniques (including machine learning) are mostly based on abstracts, but developing comprehensive corpora of full texts or key portions of full texts  would, in some cases, greatly facilitate more comprehensive and robust technology‐assisted discovery of relevant evidence and analysis of article content.3.Standardised classification frameworks and ontologies—Text analysis methods are more powerful and have broader applicability when combined with established ontologies or classification frameworks for concepts and their synonyms .4.Data extraction/coding—Automated extraction of meta‐data from full texts is a key challenge but would speed up a time‐consuming process and should focus on all aspects of the map's key elements, including study location, population type, intervention type and strength, comparator type, measured outcome, context, study design and methods. Some of this information is easily identified through text analysis  and systematic mapping to facilitate computer‐assisted “research weaving”  of broad concepts  for use in screening and coding that can be validated will facilitate rapid and comprehensive discovery and analysis of relevant evidence  would facilitate large‐scale validation of automation technologies, by allowing methodologists to compare the results of computer‐driven procedures with human‐driven results.8.More collaborative development—To harness the increasing global attention focused on the use of machine learning and other technologies in text analysis, evidence synthesis technologists (those developing tools and frameworks for automation and computer‐assistance) should work collaboratively to share data and methodological protocols and avoid wasted effort. Organisations like the Evidence Synthesis Hackathon (www.eshackathon.org) and the International Collaboration for the Automation of Systematic Reviews (icasr.github.io) are paving the way.9.Development of different types of maps—If routine tasks can be highly automated and large literatures are at least crudely machine‐synthesisable, systematic maps may no longer be limited to narrow research questions. This opens the door to very ambitious mapping efforts, at the scale of disciplines or major topic areas  to facilitate multiteam tool development and collaboration (and avoid redundancy and development waste).2.Paywalls—Many effective tools with long‐term support must charge subscription or access fees to ensure their longevity. These paywalls may be restrictive for reviewers working in resource‐constrained contexts. Waivers for low‐ and middle‐income country users and institutional subscriptions can help to support wider use, however.3.Lack of open discovery—Automation of systematic mapping requires comprehensive access to large bodies of abstracts and full texts. However, this big data is typically held by publishers and in bibliographic databases that are hidden behind paywalls, or have built‐in use restrictions that limit the volume and type of data that can be accessed. Some novel platforms and databases, such as Microsoft Academic (https://academic.microsoft.com/home), Crossref (https://www.crossref.org/), and Lens.org (https://www.lens.org/), do allow large‐scale access to bibliographic information . Open Access (freely accessible full texts) is increasing but is not yet sufficient for use in automated mapping. Even when researchers do have access to papers, obtaining full texts at scale and in a machine‐readable format is rarely possible.4.Lack of standardised validation—Many tools require robust and independent validation before they are regarded as being safe to use. However, validation has not yet been standardised and is typically self‐assessed by those producing evidence synthesis technologies. In order to validate tools, there is a need for “gold standard” datasets from example reviews, which have been scarce to date  that is not yet fully feasible with automation technologies because of the wealth of information in research articles and the nuance and implicit meanings hidden within narrative style documents. For example, the presence of a phrase in an article's methods text does not necessarily mean that method was used; “We chose to use a blocked design because of the challenges associated with randomised control trials”.4.21.Coding skill barrier—Currently, tool use sometimes requires knowledge of coding or programming ability, for example, many of the packages in the R environment  allow standardised GUIs to be produced for R packages with relative ease, reducing necessary resource investment while increasing usability.2.Perception/trust barrier—In general, people do not yet trust machines to replace humans in research tasks (O'Connor et al., 3.“Handing over to computers” barrier—If humans are used for an initial mapping and technology keeps processes up‐to‐date, what standards should be in place to ensure consistency and accuracy over time? At what point do we hand over to technology, and what procedures should be in place for verifying that they are still functioning appropriately? These questions must be answered before broad‐scale automated systematic mapping can be rolled out.5A wide variety of tools already exist to support computer‐driven systematic mapping. These tools sit on a spectrum from those intended to facilitate human‐driven mapping, to those intended to replace humans entirely. However, current technology is not yet sufficient to automate all of the processes involved in rigorous evidence synthesis. Furthermore, rigorous validation is necessary before many of these tools can be trusted for wide‐scale use by the broad research community.We have highlighted some of the main opportunities that already exist, where the key intervention points are in systematic mapping, and what developments in technologies and frameworks are needed to facilitate the increased use of evidence synthesis technology in systematic mapping. We believe that systematic mapping lends itself well to at least partial automation and call for the methodology and tool development community to collaborate to reduce redundancy and increase the efficiency of evidence synthesis technology development and integration.


Anti-Black racism has strong roots in American health care and medical education. While curricula on social determinants of health are increasingly common in medical training, curricula directly addressing anti-Black racism are limited. Existing frameworks like the Presence 5 framework for humanism in medicine can be adapted to develop a novel workshop that promotes anti-racism communication.We performed a literature review of anti-racism collections and categorized anti-racism communication practices using the Presence 5 framework to develop the Presence 5 for Racial Justice Workshop. Implementation included an introductory didactic, a small-group discussion, and a large-group debrief. Participants evaluated the workshop via an online survey, and we analyzed the resulting qualitative feedback.A total of 17 participants took part in two workshops, with nine of the participants responding to the evaluation survey. Themes that emerged from survey responses included strengths of and improvements for the workshop structure  and content .The workshop provides participants with a semistructured discussion around the five anti-racism communication practices. Barriers to implementation include incorporating the workshop into existing curricula and ensuring diverse learners. Barriers to evaluating the workshop include the low survey response rate. Recommendations to improve the workshop include using case-based discussion and varying the workshop structure according to institutional needs. Next steps include an implementation study to evaluate the acceptability, feasibility, and effectiveness of the workshop. Events in 2020, including George Floyd's murder and the co-occurrence of marked racial health inequities, prompted a reckoning on anti-Black racism and the need for anti-racism communication that focuses on the unique lived experiences of Black patients.7 Urgent changes are needed to work towards racial health equity for Black patients, starting by teaching learners how to combat anti-Black racism directed at Black patients by the health care system and clinicians.Race is socially constructed, and racism is a belief in racial hierarchy.8 Humanism-focused frameworks like the Presence 59 may be an effective approach in teaching anti-racism communication because they center the patient within the patient-physician relationship. Originally designed for clinicians and intended to address technology and administrative demands of clinical practice as well as to reduce medical errors, the Presence 5 framework seeks to foster meaningful connections between the patient and clinician by focusing on the human aspect of medicine. The Presence 5 framework fosters clinician humanism through tangible, evidence-based, interpersonal practices across five domains: (1) prepare with intention, (2) listen intently and completely, (3) agree on what matters most, (4) connect with the patient's story, and (5) explore emotional cues.9 These practices are disseminated and implemented in clinical settings through discussion groups where clinicians learn about and share how they practically use the Presence 5 to promote humanism in clinical care.Dismantling racism in medicine requires that medical education promote racial justice throughout clinical training, longitudinally integrating interventions into existing curricular structures to foster deep reflection and difficult dialogue among learners of all levels. One approach to filling the gap of anti-racism training in medical education is through an intervention that is rooted in interpersonal connection and humanism, a value that spans the ACGME six core competencies.1.10 prepare by learning established frameworks to address racism in the moment.11Prepare with intention: reflect on identity and power dynamics,2.12Listen intently and completely: listen for racism-related factors influencing health without interrupting.3.15Agree on what matters most: allow patients to direct the conversation around racism and health.4.16 identify barriers beyond a disease,17 and encourage patient advocacy11 to eliminate stigmatizing language around a patient's race.18Connect with the patient's story: learn about a patient's experiences with racism to promote dialogue on care plans,5.19Explore emotional cues: reflect, validate, and confirm a patient's emotions around racial trauma.Given a strong evidence base and practical application, Presence 5 is an ideal framework to serve as a foundation for urgently needed anti-racism training in clinical practice. Therefore, we sought to adapt the Presence 5 framework to anti-racism in medical education through a literature review and an external review by national experts in DEI to develop the Presence 5 for Racial Justice Workshop. This workshop offers a novel approach to teaching anti-racism with the following three critical features: The workshop is (1) discussion based, promoting open dialogue among diverse learners; (2) evidence based, ensuring recommended practices are rooted in the literature; and (3) practical, providing learners with usable anti-racism strategies in everyday clinical care. The In this preliminary implementation of the Presence 5 for Racial Justice Workshop, we describe lessons learned from an evaluation of two workshops.The Presence 5 for Racial Justice Workshop was developed through a literature review and external review by national experts in medical education and health equity. All authors agreed on the final wording and format of the workshop. This discussion-based workshop was intended for learners of diverse racial backgrounds and levels of medical training to foster meaningful conversation. This project was approved by the Stanford Institutional Review Board (protocol #57663) on August 17, 2020.We implemented the Presence 5 for Racial Justice Workshop through a virtual, 1-hour workshop via Zoom. The workshop was facilitated by a faculty member, fellow, and medical student to encourage dialogue across training levels. Facilitators reviewed the Presence 5 for Racial Justice Workshop guide  and the We began the workshop with a 15-minute didactic portion, during which we used screenshare functionality to show slides  reviewin12 reflecting on various aspects of their identity and what perspectives they might bring to a patient encounter.We used three breakout rooms for a 35-minute discussion, assigning facilitators to each breakout room and evenly distributing participants. We encouraged participants to turn their video on during the breakout groups with a stated goal of increasing engagement and dialogue. In the breakout rooms, we began by reading aloud the ground rules for discussion, beginning with “Racism is a challenging subject matter,” to encourage participants to respect each other and also to remind them of the mental health resources available in Next, we presented a case, stopped the screenshare, and spent the remainder of the small group facilitating discussion on each of the five practices using the discussion questions in the Presence 5 for Racial Justice Workshop guide . ParticiFor this portion of the workshop, participants were brought back into the main virtual room to share their goals and reflections from each of the small groups. Participants shared reflections aloud, as well as in the virtual chat. At the end of the workshop, we reminded participants of the mental health resources previously provided  given th20 adding suggested practices, references, and teaching strategies.Completion of the evaluation survey was voluntary. We analyzed demographic data from participants using summary statistics, and we iteratively and systematically integrated qualitative survey feedback using a thematic content approach,A total of 17 participants completed the Presence 5 for Racial Justice Workshop. Seven internal medicine residents completed the workshop during an institutional didactic session, and a combination of 10 medical students, residents, fellows, and faculty completed the workshop during a regional general internal medicine conference. Nine of 17 workshop participants responded to the evaluation survey, for a response rate of 53%. The respondents were of diverse backgrounds, including gender, race, ethnicity, level of training, clinical setting, and DEI experience .21 with questions soliciting feedback on each of the Presence 5 for Racial Justice practices as well as workshop content and structure. Emergent themes included strengths of and improvements for workshop content and structure.The survey focused on level 1 (reaction) of Kirkpatrick's four levels of evaluation,Participants recommended improvements to the Presence 5 for Racial Justice practices by providing additional suggestions of anti-racism communication practices, specific language/phrases to use in clinical training, and additional literature, all of which were incorporated into the final workshop.Participants identified strengths of and improvements for the Presence 5 for Racial Justice Workshop content. Participants identified the guidance regarding how to have difficult conversations with patients about racism and health as a strength of the discussion. One participant commented that a helpful part of the workshop was “listening to the personal experiences we have with interacting with Black patients and stating our biases when it came to these experiences.” Another participant noted, “Advice on how to have these important conversations with patients was the most helpful part of the discussion, and the time and space to reflect on disparities and solutions to inequities was helpful.” Participants noted that the case provoked good discussion, and they appreciated sharing and listening to personal experiences about practicing anti-racism in clinical encounters.To improve the workshop content, participants noted that it might be helpful to provide prompts of possible patient comments around the topic of racism during clinical encounters coupled with discussion around how to respond to these comments.Regarding workshop structure, participants appreciated the organization of the workshop, highlighting the utility of the introductory didactic portion as well as the case-based, small-group discussion and goal setting. Participants appreciated the evidence-driven didactic portion of the workshop; one participant commented, “I appreciated the inclusion of data in the introduction materials.” Regarding improvement for the workshop structure, participants recommended having more protected time and more opportunities for discussions around racism and medicine.We successfully implemented the Presence 5 for Racial Justice Workshop to provide participants across training levels with the time and space for a semistructured, evidence-based, and insightful discussion around practicing anti-racism in medicine. We believe this is the first adaptation of a humanism-based framework to develop a workshop on anti-racism communication for diverse learners. The overall objectives were met, and this novel workshop adds to the growing and evolving repository of medical education efforts dedicated to addressing racism in medicine.N = 9), likely due to increasing demands during the COVID-19 pandemic. As this was a preliminary project to enable a larger implementation study, we solely focused on level 1 of Kirkpatrick's four levels of evaluation.21 Due to pandemic restrictions, these workshops were delivered virtually, which may have limited some aspects of learner engagement. The benefit of the virtual nature of these workshops, however, was the opportunity to involve a geographically diverse group of participants, which added to the richness of the discussion.There were barriers to implementing the Presence 5 for Racial Justice Workshop. The absolute number of participants was low due to lower virtual conference attendance rates. Similarly, the number of participants who completed the survey was low (22 but it is unclear if these will be lasting and sustainable efforts.Participants noted the importance of carving out time for regular and ongoing discussions around anti-racism, yet a major barrier was finding the time within existing curricula during medical training. Several institutions have followed national recommendations around developing anti-racism medical education curricula,23Finally, the Presence 5 for Racial Justice Workshop provided communication practices to address anti-Black racism aimed towards patients by the health care system and clinicians. While this is a crucial step towards health equity, there is a need for trainings aimed at addressing anti-Black racism towards Black learners in medical education, whether coming from patients, other learners, or faculty. This is vital to creating a culture of inclusion as well as supporting the pathway of Black learners into health care fields.24 so as not to overburden facilitators of color with the task of teaching anti-racism communication in medicine. We recommend emphasizing the evidence base as the foundation of this workshop, as participants appreciated this as a major strength of the workshop.We recommend implementing this workshop using a case-based discussion. Participants appreciated the case as a practical way to spark discussion around anti-racism practices in the clinical setting. We also recommend all workshop facilitators review There may be various ways to structure this workshop, depending on institutional resources; given the time and depth needed for discussion on these important topics, the workshop could include a five-part series with discussions for each of Presence 5 for Racial Justice practices. Alternatively, small groups could talk about one Presence 5 for Racial Justice practice each and share reflections through a teach-back with the larger group.To further evaluate the Presence 5 for Racial Justice Workshop, an implementation study is under development within undergraduate and graduate medical training. Evaluations will consider the acceptability and feasibility of the discussion circles format, as well as the effectiveness of building knowledge, skills, and confidence around anti-racism communication practices. The long-term goals of implementing Presence 5 for Racial Justice Workshop within medical education are to transform the culture and practice of medicine, foster humanism in clinical encounters, and promote health equity for Black patients.Presence 5 for Racial Justice Guide.docxIntroductory Didactic.pptxParticipant Resources.docxSurvey.docxAll appendices are peer reviewed as integral parts of the Original Publication.


The European Society of Cardiology has published updated guidelines regarding pathways for diagnosis and management of obstructive coronary artery disease (CAD). Non-invasive functional assessment, for example, by stress perfusion cardiac magnetic resonance (stress pCMR) is recommended in patients with intermediate pretest probability of disease. Previous pCMR studies were mainly performed in high volume university hospitals with experienced radiologists or cardiologists interpreting the images.The aim of the present study was to evaluate the feasibility of establishing a stress pCMR imaging service in a district hospital.One hundred and thirteen patients with intermediate pretest probability of CAD referred for single-photon emission computed tomography (SPECT) at the regional hospital also underwent adenosine stress pCMR locally. The diagnostic analysis was compared to that of an experienced cardiac magnetic resonance (CMR) center serving as a reference.k = 0.34 and 0.51). No improvement in agreement between reference reader and local reader during the study was demonstrated.Inter-rater agreement between local readers and the reference reader was substantial to perfect for late gadolinium enhancement (LGE) (weighted kappa = 0.76 and 0.82), but only fair to moderate for pCMR (CMR is feasible in patients with intermediate pretest probability of obstructive CAD in the setting of a district hospital. However, as opposed to infarct detection with LGE, the interpretation of stress pCMR was more challenging. To establish this method, we suggest obtaining experience in close collaboration with a reference CMR center. For patients in the lower range of PTP, a non-invasive diagnostic approach is advised. When a low clinical likelihood of CAD is suspected and patient characteristics suggest high image quality, anatomical assessment by computed tomography angiography of the coronary arteries (cCTA) is the preferred diagnostic pathway. In cases of intermediate or higher likelihood of disease and when revascularization is contemplated, a functional imaging test is recommended either by single-photon emission computed tomography (SPECT) or by stress perfusion cardiac magnetic resonance (stress pCMR).The European Society of Cardiology (ESC) recently updated their guidelines for the diagnosis and management of obstructive coronary artery disease (CAD).3 Furthermore, in contrast to SPECT, stress pCMR has the advantage of no ionizing radiation,4 no attenuation artifacts, and better spatial resolution. Previous studies comparing SPECT and stress pCMR were mainly performed in high volume university hospitals with experienced radiologists or cardiologists interpreting the images.Studies have documented that pCMR correlates better with findings of ICA than SPECT.Currently, pCMR for diagnostic work-up in suspected CAD is not in routine use in Norway. This may be due to diagnostic traditions, lack of necessary equipment, MRI capacity, local expertise, or expected need for extra resources when compared to SPECT, which is the more widespread method.5 In the present study, we evaluated the feasibility of establishing a service of stress pCMR. We compared our in-house interpretation of obtained images to that of an experienced CMR center.Successful implementation of a cCTA service in a district hospital setting has been demonstrated.This single center cohort study was conducted at a Norwegian district hospital serving 300.000 inhabitants. All participants provided written informed consent prior to entering the study. The study was approved by the Regional Committee for Medical and Health Research Ethics in Norway (REK 2010/3219).Patients were recruited from the outpatient cardiology clinic in our hospital and from four practicing cardiologists in our catchment area in the period of April 2011 to August 2013. The criterion for inclusion into the study was a planned referral for SPECT. Indications for SPECT were either evaluation of suspected symptomatic stable CAD in patients with intermediate pretest probability of obstructive CAD or evaluation of a previously demonstrated borderline coronary artery stenosis. Pretest probability of obstructive CAD was evaluated at the discretion of the referring clinician.2), communication problems, claustrophobia, inability to lie in a supine position for an hour, age below 30 or above 75, or contraindications to CMR or adenosine.Exclusion criteria were atrial fibrillation, previous coronary artery bypass surgery, severe renal failure  and ischemia by adenosine stress pCMR. Subsequently, the patients were examined with SPECT. We did not record changes in symptoms or medication in the period between the two examinations.Between March 2019 and April 2020, all CMR examinations were retrospectively reassessed by two local radiologists and one cardiologist at the CMR reference center . After 10, 20, and 50 cases, respectively, we held telephone conferences between local and reference readers to facilitate learning. We did not retrospectively alter diagnostic evaluations after these sessions. The readers were blinded to patient history and to the other reader’s conclusions. The local radiologists had assessed 318 and 399 non-perfusion CMR respectively before start of this project, and had been consultants for 10 and 11 years. However, they had no prior experience in the performance and interpretation of pCMR. The reference reader had 10 years of CMR experience, reporting more than 400 cases annually.1 was calculated retrospectively based on registered symptoms at time of inclusion.Pretest probability of CAD according to the ESC 2019 guidelinesThe CMR examinations were performed with a 1.5 Tesla Siemens Avanto scanner . For dynamic stress, all patients received an adenosine infusion of 140 μg/kg body weight/minute. After 3 minutes of infusion, a contrast injection with 0.05 mmol/kg dimeglumine gadopentetate  at a flow rate of 5 mL/s was started. Simultaneously, the stress pCMR image acquisition was initiated. The patient was asked to stop breathing when contrast arrived in right ventricle. The image acquisition lasted for 120 heartbeats with three short-axis slices sampled on each heartbeat. Adenosine infusion was stopped after approx. 50 heartbeats. We applied the following imaging parameters: Saturation recovery segmented gradient echo pulse sequence with TR/TE/TI of 167/1.11/120 ms, 108 × 144 matrix, 340–430 mm field of view, 1 NEX, 8 mm slice thickness.After 10 minutes, rest of the pCMR imaging was performed without adenosine infusion, but with otherwise identical contrast parameters and pulse sequence parameters.After another 10 minutes, LGE imaging was performed with 3 long-axis slices and short-axis slices that covered the entire left ventricle. Imaging parameters are phase sensitive gradient echo pulse sequence triggered on every second heart beat in diastolic phase with typical TR/TE/TI of 800/3.33/300 ms, 156 × 256 matrix, 330 mm field of view, 1 NEX, 8 mm slice thickness.6 was filled in for all patients. Each segment was assessed for perfusion and late gadolinium enhancement (LGE) pathology. The diagnosis of perfusion defect was based on a visual analysis with comparison between regions to identify relative hypo-perfusion according to current guidelines from the Society of Cardiovascular Magnetic Resonance.7 A comparison between stress and rest images was performed to identify inducible perfusion defects and artifacts. Perfusion defects in regions with LGE were only interpreted as reversible if the extent of the perfusion defect was clearly beyond the extent of LGE.For CMR, a 16 segment score sheet, where the apical part had been excluded from a 17 segment sheet,8For evaluation of ischemia and infarct, a score was assigned to each segment indicating a normal (0), borderline (1), or pathologic (2) finding. The final overall score for LGE was deemed pathologic if at least one of the segments was classified as pathologic with a high degree of confidence. Similarly, the final score for pCMR was deemed pathologic if there was at least one segment with a high confidence of transmural pathology or two adjacent segments with high confidence of subendocardial pathology.R, GE Healthcare). For stress, bicycle exercise testing was performed in 96 patients. In 20 patients not able to perform bicycle exercise, adenosine stress was applied.Gated SPECT was performed with a dual head cardiac gamma camera , with low energy high resolution collimators. Stress and rest studies were done in a one-day protocol using 99mTc-tetrofosmin .Clinical characteristics were expressed as percentages or medians with inter quartile range as appropriate. Agreement between local and reference CMR center interpretations was calculated by using the weighted Cohen’s kappa (k). Confidence intervals for the kappa statistics were calculated from 2000 bootstrap replications. The level of agreement for a kappa value 0–0.20 was interpreted as slight, 0.21–0.40 fair, 0.41–0.60 moderate, 0.60–0.79 substantial, and 0.81–1.00 almost perfect.A total of 113 patients were included in the study. With regard to the perfusion findings , there wThere was no statistically significant change in agreement either for LGE or stress pCMR during the study period when comparing Cohen’s kappa for the first 56 patients vs. the last 57 patients .Table 4.SPECT was performed in 107 of 113 patients. Median time between CMR and SEPCT was 33 days (IQR: 20–47 days). Two patients were not referred to SPECT for unknown reasons. Two patients did not attend to SPECT in spite of referral. Two patient developed symptoms of acute coronary syndrome while waiting for SPECT. Both of these patients were referred to ICA and had percutaneous transluminal coronary angioplasty (PTCA) performed. As shown in ICA was performed within 12 months in a total of 16/113 CMR patients and 14/107 SPECT patients . Only onIn this study, we examined the feasibility of establishing a perfusion CMR imaging service in a district hospital. The locally obtained diagnostic results were compared to that of readings at an experienced CMR center serving as a reference. Although it was expected that the agreement would be better for conventional CMR  than for stress perfusion pCMR, we considered it relevant to record the level of agreement between a reference center and a district hospital after a limited amount of training. We consider our results to be relevant to other district hospitals that consider starting a stress pCMR service as they might illustrate how guidelines may be implemented in practice.k = 0.76 and 0.82), but only fair to moderate agreement for diagnosis of ischemia with pCMR (k = 0.34 and 0.51). Furthermore, pCMR agreement was not improved during the study period. In contrast to the high accuracy and reliability of CMR in cardiac function and LGE imaging, pCMR is known to be adversely affected by multiple factors during data acquisition as well as post-processing.10 Chih et al.11 previously found a high interobserver reproducibility  of stress pCMR in patients with multi-vessel CAD and low risk for CAD. Muhling et al. found good interobserver agreement using semi-quantitative analysis provided the quality of images was good.12 However, in the MR-IMPACT study13, the reader agreement was only fair, with a kappa of 0.30–0.39 which is in line with our results. The present study expands the current literature regarding the interobserver agreement of pCMR imaging in a district hospital. Although not directly underpinned by our results, we speculate that the results would further improve by continued training. However, more cases than we had available in our study are necessary to ensure adequate training in stress pCMR.The inter-rater agreement analysis showed substantial to perfect agreement for diagnosis of infarction with LGE  by CMR (according to the reference reader). In contrast, only 10/107 (9%) had ischemia as diagnosed by SPECT. Collectively, these data may indicate that there might be a substantial proportion of false negative SPECT examinations in our study and/or the CMR readings were too sensitive.In a district hospital setting, the prevalence of obstructive coronary artery disease is expected to be lower than in university hospitals receiving more selected patient groups. Standard imaging to rule out CAD in our region is cCTA or SPECT depending on clinical probability. We suspected a significant referral bias in our material. Direct referral to ICA bypassing other non-invasive imaging tests may have influenced our results. However, the prevalence of ischemia according to the reference reader was comparable with expected pretest probability of CAD. Furthermore, it is unlikely that a selection bias has affected our results when it comes to the comparison between local readers and reference readers.14 it has been a particularly vexing syndrome for clinicians to evaluate and manage, as there are no widely available non-invasive imaging tests that can identify such patients with reasonable accuracy.One of the main strengths of pCMR is the detection of microvascular angina due to coronary microvascular dysfunction (MvD) in the setting of non-obstructive coronary artery disease. Although MvD would account for the patients’ symptomatology in up to 50% of all angina cases and comes with an increased risk of major adverse cardiovascular events,15 and this would obviously not be confirmed with angiography, which is expected to be unremarkable in these cases. As such, the potentially increased detection of MvD with pCMR could be one of the major confounding parameters leading to significant discrepancy between the patient’s symptoms, pCMR, SPECT, and angiographic findings.Patients with MvD can safely be assessed using pCMR, both with quantification but also visually, in which case the entity presents as a global circumferential subendocardial defect at stress. As the accuracy of our local experience would only be optimally assessed against positron emission tomography (PET) perfusion quantification or more sophisticated invasive coronary measurements , it is not possible to establish the exact extent of MvD in our cohort. However, in 15/113 cases analyzed by the reference reader, a perfusion pattern suggestive of microvascular dysfunction was identified. This finding should be carefully taken into consideration in the interpretation of our results, as pCMR is superior to SPECT for the detection of MvD,There are limitations in this study. This was a single center study involving only one reference reader and two local readers. However, the reference reader had completed training at a large-volume cardiovascular magnetic resonance core lab . Nevertheless, involving multiple reference readers might have strengthened our results further by reducing the possibility of individual reader bias. Furthermore, all CMR examinations were performed in the period 2011–2013. Modern scanners have improved image quality. Improved image quality would probably have contributed to improved interobserver agreement, especially in pCMR.In conclusion, we hold it feasible to establish and run a pCMR service at a district hospital. We conclude that the diagnosis of ischemia by stress pCMR was more challenging than LGE imaging. To secure sufficient quality in pCMR imaging and interpretation, we hold it essential that a close collaboration with a reference center is established to attain appropriate experience in image analysis.


Immunoglobulin A vasculitis (IgAV) nephritis, also known as Henoch-Schönlein purpura nephritis (HSPN), is a condition in which small blood vessel inflammation and perivascular IgA deposition in the kidney caused by neutrophil activation, which more often leads to chronic kidney disease and accounts for 1%–2% of children with end-stage renal disease (ESRD). The treatment principles recommended by the current management guidelines include general drug treatment, support measures and prevention of sequelae, among which the therapeutic drugs include corticosteroids, immunosuppressive agents and angiotensin system inhibitors. However, the concentration range of immunosuppressive therapy is narrow and the individualized difference is large, and the use of corticosteroids does not seem to improve the persistent nephropathy and prognosis of children with IgAV. Therefore, individualized maintenance treatment of the disease and stable renal prognosis are still difficult problems. Genetic information helps to predict drug response in advance. It has been proved that most gene polymorphisms of cytochrome oxidase P450 and drug transporter can affect drug efficacy and adverse reactions (ADR). Drug therapy based on genetics and pharmacogenomics is beneficial to providing safer and more effective treatment for children. Based on the pathogenesis of IgAV, this paper summarizes the current therapeutic drugs, explores potential therapeutic drugs, and focuses on the therapeutic significance of corticosteroids and immunosuppressants in children with IgAV nephritis at the level of pharmacogenomics. In addition, the individualized application of corticosteroids and immunosuppressants in children with different genotypes was analyzed, in order to provide a more comprehensive reference for the individualized treatment of IgAV nephritis in children. Immunoglobulin A vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common systemic vessel vasculitis in children. It’s a kind of immune sediment dominated by IgA and usually self-limiting, which often affects the skin (which can touch purpura), gastrointestinal tract, lungs, joints, nervous system, urinary system, and renal . The incCurrently, in addition to the widely recognized renin-angiotensin system (RAS) inhibitors, drugs such as corticosteroids (CS) and various immunosuppressive agents are often recommended for IgAV nephritis in the presence of proteinuria to stifle renal damage . HoweverGenetics is and mayone of the most common factors associated with drug response, and having genetic information about patients can help predict drug response in advance. Due to the narrow concentration range of immunosuppressive drug therapy, pharmacogenomics is expected to be one of the most promising tools in the field of immunosuppressive drug therapy. It may help select appropriate drugs for children with IgAV nephritis and individualize the dose . In thisIgAV nephritis is a typical acute glomerular inflammatory disease caused by autolytic vasculitis. It is due to mesangial proliferative changes caused by aberrant glycosylation of IgA1 sedimentation in the glomerulus. At present, the precise mechanism for this situation is unclear. In addition to IgA1 deposition, IgAV nephritis has also been found to be correlated with immune factors, including immune complexes, and its incidence is positively correlated with plasma IgG and IgE levels and type 1 allergic reactions .IgAV is a vasculitis of small vessel leukocyte fragmentation; compared with the clinical manifestations of adult IgAV nephritis, children’s IgAV nephritis clinical manifestations are different . In 95% IgAV nephritis can be manifested as hematuria with or without albumin urine, nephropathy and/or idiopathic nephrotic syndrome under the microscope (and/or visible to the naked eye), and/or purpura, colic, bloody stools, edema, and joint pain. In general, IgAV nephritis is somewhat self-limited and may recover without treatment. Children with mild IgAV nephritis have a good prognosis but may develop permanent renal damage and scarring if not diagnosed and treated early . IgAV ne2) = 36.2 × height (cm)/serum creatinine (μmol/L). However, the formula is derived from GFR in children 15–75 ml/min/1.73 m2, and it may be invalid if GFR exceeds this range  to evaluate the comprehensive renal function. Urine analysis (morning urine samples) should confirm hematuria, proteinuria, and/or proteinuria quantification and urine protein: urine creatinine ratio (UP: UC ratio) . The calis range . The claRecent studies have confirmed that individuals with IgAV nephritis have a strong genetic susceptibility. It is correlated with human leukocyte antigen (HLA), especially in its type II region . CurrentOther studies have also shown that susceptibility to IgAV nephritis is associated with genetic polymorphisms outside the HLA region, containing genetic polymorphisms that regulate vascular homeostasis, new angiogenesis, and gene polymorphisms that encode aberrant glycosylation of IgA1. It was 2) should be treated with ACEI or ARBs.It has been shown that blocking the RAS is beneficial to renal function . RegardlThe efficacy of RAS blockers on IgAV cannot be clearly demonstrated. Still, clinical studies suggest that RAS blocker use has a favorable impact on the nephritic outcomes of patients with IgAV. In a recent study , proteinThe potent anti-inflammatory effect of CS can inhibit the rapid deterioration of renal pathology in the IgAV patients’ population to a certain extent, especially in diminishing urinary protein and postponing the renal function decline. In patients’ serum, CS can reduce the aberrant o-glycosylation of IgA1, thereby reducing the latter’s deposition in the glomerular capillary wall and mesangial. The guideline of 2012 KDIGO recommended that patients with persistent proteinuria be treated with CS for 6 months after using ACEI or ARBs . In the Significantly, long-term CS administration can induce the inhibition of growth and development, osteoporosis, diabetes, adrenal inhibition, and Cushing syndrome . More imGlucocorticoid is a kind of CS classification, and NR3C1 is a gene that codes glucocorticoid receptor (GR). NR3C1 mutations can reduce the transcriptional activity of genes or even lose the activity of protein expression products, affecting GR’s formation and then impacting GR’s response to CS, resulting in CS resistance. Many studies have shown that NR3C1 is closely related to CS resistance in nephrotic syndrome . These SCRHR1 is the key factor that mediates corticotropin-releasing hormone (CRH) to stimulate adrenocorticotropic hormone (ATCH) to secrete CS, which is indispensable in the secretion of human CS. If the CRHR1 gene is mutated, it can reduce or lose the gene’s function and inhibit the increased secretion of CS stimulated by inflammation by decreasing the secretion of ACTH. Therefore, the genetic variation of CRHR1 may be the most useful marker to identify the deficiency of endogenous CS and respond better to exogenous CS. Based on this theory, studies have shown that CRHR1 gene variants  can enhance the efficacy of CS in asthma .Moreover, a variety of GLCCI1 mutated alleles are mainly associated with the efficacy of CS . CurrentSTIP1 is a coordinated GR receptor chaperone protein that participates in CS binding and activating of intracellular GR complex and plays an anti-inflammatory role. STIP1 gene variation may regulate the CS response of asthma patients with impaired pulmonary function . FurtherIn addition, in idiopathic nephrotic syndrome pediatric, the 1236C > T polymorphism, one of the ABCB1 (belonging to ABC) gene mutations, may be associated with CS resistance, and the T allele and TT genotype may be closely associated with resistance and may require other therapeutic strategies . Here, wCyclophosphamide (CYC) can inhibit the function of T cells and B cells and then reduce or prevent abnormal immune complexes sludging in glomeruli . CYC is in vivo can be ten times different when ordinary people take the same amount of CYC  and CYP2B6*4 (c.785A > G) mutations increased enzyme activity, which significantly increased the risk of ADR  for people with these allele mutations . In cont2, the mutation does not affect the metabolic level of CYC  . Whereasl of CYC . It is sl of CYC . Oppositl of CYC .CYP2C9 and CYP3A4 play fewer roles in CYC activation. CYP2C9*2 (c.430C > T) and *3 (c.1075A > C) may increase the risk of leukopenia, but, interestingly, they may have a preferable effect on the therapeutic regimen . A betteGlutathione S-transferase (GST) is a phase II metabolic enzyme that can inactivate CYC and its intermediate metabolites, including GSTA1, GSTP1, GSTT1, and GSTM1. In a recent study on the mutation of GSTA1, it was found that compared with wild-type and heterozygous carriers carrying GSTA1  T allele, patients with a homozygous mutation of GSTA1  T allele were prone to unresponsiveness to CYC and more likely to be toxic . IncreasIn vivo, a vital substance first converted from MMF is Mycophenolic acid (MPA). The MPA can downregulate the activity of inosine monophosphate dehydrogenase (IMPDH) in the critical pathway of purine synthesis, blocking the T and B lymphocytes proliferation and differentiation, thus effectively inhibiting the renal damage caused by abnormal immune reactions (Mycophenolate mofetil (MMF) and azathioprine (AZA) are often regarded as immunosuppressants of the same recommended level in IgAV glomerulonephritis, and both are prodrugs. eactions . After eCompared with the 2012 KDIGO guidelines, the recommendations of immunosuppressants such as CYC, MMF, and AZA were more positive by subsequent evidence-based consensus or guidelines. In China, experts support CS combined with immunosuppressants in treating severe IgAV nephritis in children . The recMPA has biological activity as an intermediate from MMF and can inhibit IMPDH. It is catalyzed and transformed by uridine diphosphate glucuronosyltransferase (UGT). Most MPA is transformed by UGT1A9 into 7-O-MPA-glucuronide (7-O-MPAG) without activity, and a small part of MPA is transformed into Acyl-MPA-glucuronide (AcMPAG) by UGT2B7 . RemarkaIt is reported that IMPDH can be divided into IMPDH type I and type II . A studyin vivo metabolic process of MPA in patients with renal transplantation  or UGT1A9  mutation genes located in the gene promoter region , which mantation . Howeverantation . This diAZA is prone to myelosuppression, mainly caused by excessive induction of thioguanine nucleotides, an intermediate metabolite. The prevailing view is that the TPMT alleles are critical in this step because mutations in the TPMT gene result in reduced or absent enzyme activity, causing a considerable accumulation of approximately 90% of thioguanine nucleotides that cannot be converted. Compared with adults, the TPMT activity of children is almost the same as that of adults . AlthougFurthermore, mutations in the nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) gene have been reported as a more predictive predictor of AZA-induced leukocytopenia in Asian patients than TPMT. The low frequency of TPMT mutations in Asian populations may make NUDT15 more dominant in the use of AZA. A meta-analysis found that NUDT15*2 and *3 were critical genetic markers of early myelotoxicity elicited by thiopurine drugs (including AZA) in Asians . The NUDIn addition to the gene polymorphisms of TPMT and NUDT15, the allelic variation of inosine triphosphate pyrophosphatase (ITPA) during AZA metabolism also affects ADR. Most mutations in ITPA genes lead to a decrease in the bioactivity of ITPA, and the primary mutations are ITPA , in which c.94C > A pure and mutation almost inactivate the enzyme . Low ITPCyclosporin A (CyA) has rich application experience in various immune diseases and organ transplantation as a calcineurin inhibitor, but few studies have been conducted in children with IgAV nephritis. in vivo, while a similar drug, Tacrolimus (TAC), is mainly metabolized by CYP3A5. Compared with CYP3A5, which mainly plays a role in the kidney, CYP3A4 metabolizes most CyA in the liver, and its variant CYP3A4*22  was related to the decline of enzyme bioactivity expressed in the liver, which is also related to individual clearance declining and renal toxicity  also have affected the pharmacokinetics (PK) of CyA. As one of the sensitive substrates of P-gp, the bioavailability of CyA is low. P-gp, a member of the ABC membrane transporter family (including ABCC2 and ABCG2), is a product of human multidrug resistance gene 1 (MDR1). It has been discovered that adults carrying the POR*28 allele require more CsA dose , while Atoxicity .via CYP3A isoforms (CYP3A4 and CYP3A5) in the hepar and intestine, while TAC is the substrate of the multidrug efflux transporter P-glycoprotein which is epitomized by the ABCB1 gene and previously known as MDR1; and it is represented on a multitude of epithelial cells, endotheliocyte, and lymphocytes  is an antimetabolic drug that exerts immunosuppressive effects by inhibiting lymphocyte proliferation . The repin vivo exposure . In vitro studies suggest that activation of LEF may be associated with CYP4501A2, CYP2C19, and CYP3A4  is a comparatively new oral immunosuppressant that disrupts T and B cell function by inhibiting dihydronucleic acid dehydrogenase (the rate-limiting enzyme for ab initio synthesis of pyrimidine nucleotides), specifically inhibits T-dependent autoantibody formation; and a few tyrosine kinase signaling molecules involved in immune function are also inhibited by LEF . The curd CYP3A4 , and onld CYP3A4 . Furtherin vitro . So ABCGin vitro . OverallRituximab (RTX), a monoclonal antibody against the B-cell CD20 antigen, was initially conceived and endorsed in 1997 for the therapy of non-Hodgkin’s B-cell lymphoma and, as such, has been used in many immune-mediated diseases, for example, has become the standard therapy for inducing remission and maintaining resolution in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis . StudiesIn case reports with adult patients with IgAV nephritis , RTX wasvia the alternative or lectin pathway  in 2007 demonstrated that complement inhibitors could treat rare (auto) inflammatory diseases . Many neThe current results of many basic studies support the idea that complement activation can play a critical role in the development and progression of IgAN disease; for example, narsoplimab appears to significantly reduce proteinuria and increase the stability of EGFR in renal function in high-risk IgAN patients . Since tAbnormalities in the coagulation and fibrinolytic systems can contribute to the development of IgAV nephritis ; and actChinese medicine treatment has been considered an effective treatment for children with IgAV nephritis; its combination with immunosuppressants and CS produces additional positive effects, such as alleviating blood hypercoagulability in children, reducing proteinuria, and decreasing the recurrence rate of IgAV nephritis in children . TripterPlasmapheresis (PP) has become a typical extracorporeal circulation blood purification therapy, and studies on the treatment of IgAV nephritis in children with PP or PP combined with drug therapy have proved beneficial.The mechanism of PP treatment for IgAV nephritis in children is still unclear. The results of test indicators and immunology show that PP can remove IgA-containing immune complexes or accumulations of pro-inflammatory mediators, and reduce fibrous protein or other blood coagulable factors. It is speculated that these mechanisms are related . OverallSeveral current studies have shown that tonsillectomy is not only related to the reduction of urinary protein excretion but also can effectively treat IgAV nephritis in children and prevent the recurrence of IgAV nephritis in children . There wThe mechanism of tonsillectomy in the treatment of children with IgAV nephritis is not yet clear. According to the remarkable influence of tonsillectomy on proteinuria in children’s IgAV nephritis, it can cut down the production of IgA and the aberrant immunoreaction and inflammation after glomerular deposit IgA, which is different from the IgA immune compound removed by PP, suggesting that tonsil may act the part of the pathogenesis of IgAV nephritis . On the IgAV nephritis is mainly due to renal involvement caused by aberrant o-glycosylation of IgA1 deposition in the renal. The ultimate object of its therapy is to relieve or even eliminate the long-term harm of IgAV to the kidney. Drug therapy for IgAV nephritis includes ACEI/ARBs, CS, CYC, MMF, and AZA. The evidence quality of these drugs is high, and the guidelines recommend. Potential drug therapy includes CyA, TAC, MEB, LEF, RTX, complement inhibitors, anticoagulant antiplatelet drugs, and traditional Chinese medicine. Non-drug therapy is mainly PP and tonsillectomy, which can be used as an alternative treatment or potential treatment for drug-resistant cases, recurrent cases, and refractory cases. This paper also emphatically discusses the therapeutic significance of CS and immunosuppressants on children with IgAV nephritis at the level of pharmacogenomics and analyzes the individualized application of CS and immunosuppressants on children with different genotypes to provide a more comprehensive reference for individualized treatment of children with IgAV nephritis. Pre-identification of genes that affect drug efficacy and toxicity can predict the response of individual patients to drug treatment in advance, thus helping to determine a more effective initial dose and maintenance dose and even choose a more appropriate treatment for IgAV nephritis. It can also provide genetic evidence for post hoc analysis of drug resistance and ADR. The implementation of pharmacogenomics detection can help many Chinese children achieve better treatment outcomes . TherefoCS-related gene polymorphism is associated chiefly with CS resistance, especially NR3C1 gene polymorphism, but there is a lack of related research in patients with IgAV nephritis, especially in children. Therefore, NR3C1 and other related gene polymorphisms on CS responsiveness in other diseases apply to IgAV glomerulonephritis, which still needs further research to confirm its universality.Most CYC-related genetic variations are associated with ADR, such as the higher risk of hemorrhagic cystitis and leukopenia associated with CYP2B6 and GST gene polymorphism . UnfortuThe most significant advantage of MMF is that it is safer than other immunosuppressants, and its gene polymorphism is more associated with curative effects than toxicity and is often studied in patients with renal transplantation. The research is still immature. For example, the research results in IMPDH and UGT1A9 have some contradictions and differences.The Clinical Pharmacogenetics Implementation Consortium (CPIC) suggested that TPMT deficiency was detected by identifying TPMT allele variants or TPMT phenotypes associated with the inactivation of AZA active metabolites and gave strong dose recommendations for the use of AZA in IBD patients . These rSeveral studies have shown that CYP3A4, CYP3A5, POR, ABC, and other gene polymorphisms are related to the individual differences of CyA to a certain extent, and they all can become factors that predict CyA response in advance. Unfortunately, the uncertainty of efficacy and toxicity of CyA in the IgAV population is an indispensable reason limiting the expansion of such research in the past and future.Like AZA, the research on the relationship between gene polymorphism of TAC metabolizing enzyme CYP3A5 and drug dose is relatively mature in the renal transplantation population. Therefore, to use TAC more safely, it is recommended that prior CYP3A5 typing be performed before some solid organ transplants such as heart, kidney, and lung transplants . CPIC alFor the objects of gene detection, there is no guiding principle for gene detection of children with IgAV nephritis, and there is no relevant research. However, according to the AZA genotyping guidelines , geneticThere are still some limitations here. The most important of these is the lack of drug-related genetic polymorphism studies in children with IgAV nephritis, which are currently limited to studies in other diseases, such as AZA in IBD and TAC in the renal transplant population, and the paucity of authoritative guidelines for patient genotype-based drug use and clinical evidence for physicians and pharmacists. Indeed, genetic testing increases the cost of treatment for children. It is unclear whether the increase in treatment cost is proportional to the improvement in therapeutic efficacy and safety. Despite the relative maturity of genetic testing technology, many medical institutions have not been able to implement this technology, which is related to the lack of pharmacy technicians, small patient populations, and physician attitudes toward genetic testing.In conclusion, it may not be the best time for pharmacogenomics to guide the dosing of children with IgAV nephritis, but with the vision of precision dosing, our attention to pharmacogenomics should not be diminished, especially for drugs like AZA, which can already guide dosing based on patient genotype. Therefore, the future treatment of IgAV nephritis in children urgently needs high-quality pharmacogenomics-related clinical trials to provide more evidence-based medical and pharmacological evidence for clinical diagnosis and treatment.


There is emerging evidence that implementation of an automated hand hygiene monitoring system (AHHMS) must be part of a multimodal hand hygiene (HH) program that includes complementary strategies. There are few published studies describing in detail the intervention strategies used with an AHHMS.An AHHMS that provides group HH performance rates (100 x HH product dispenses divided by the number of room entries plus exits) was implemented on two Acute Care (AC) units and six long-term care (LTC) units at a Veterans Affairs Medical Center from March 2021 through April 2022. After a 4-week baseline period and 2.5-week washout period, the 52-week intervention period included many components, such as weekly huddles, unit nurse manager engagement, vendor provided clinician-based training and feedback, leadership support, unit recognition, signage and development of a new slogan to remind colleagues to perform HH. Statistical analysis was performed with a Poisson general additive mixed model.p < 0.0001) [Figure 1]. The median HH rate increased from 17.5 to 20.0 (p < 0.0001) in LTC units and from 22.9 to 27.2 (p < 0.0001) in AC units. The intervention increased the use of hand sanitizer from 57.5% during baseline to 65.1% (p < 0.0001). The increase in HH rates was due to HH events increasing from 88,758 dispenses during the baseline to 123,722 dispenses during the last 4 weeks of the intervention. Direct observation results during the same periods showed HH compliance ranging from 61-86%.During the 4-week baseline period, the median HH performance rate was 18.6  for all 8 units. During the intervention period, the median HH rate increased to 21.6 , and during the last 4 weeks of the intervention period (exactly 1 year after baseline), the 8 units exhibited a median HH rate of 25.1 , (The green curve shows the change in the median HH rate during the intervention period compared to the baseline and washout periods, with vertical bars showing 95% confidence intervals for the monthly HH rate.The intervention increased hand sanitizer usage and HH performance rates for all units. AC units were consistently better than LTC units, which have more visitors and more mobile veterans. Further HH improvement will rely on continued implementation of complementary strategies and long-term monitoring.James W. Arbogast, PhD, GOJO Industries, Inc.: employee Pamela Wagner, RN MSN CPPS, GOJO Industries, Inc: Employee of GOJO Gregory A. Robbins, BS, GOJO Industries, Inc.: Current employee of GOJO Industries, Inc. Albert E. Parker, PhD, GOJO Industries: Advisor/Consultant John M. Boyce, MD, Diversey: Advisor/Consultant|Diversey: Expert Testimony|Diversey: Travel support|GOJO Industries: Advisor/Consultant|GOJO Industries: Expert Testimony|GOJO Industries: Travel support|Sodexo Healthcare: Advisor/Consultant.


This study validates a VR supermarket as a research tool by studying the influence of the food shopping setting on consumers’ price memory—an important antecedent for price comparisons in the purchase situation. In a quasi-experiment, two groups of consumers were given a shopping task in either a physical supermarket or a virtual reality supermarket setting. Upon task completion, participants’ explicit and implicit price memory was measured across three food product categories . Results revealed no significant difference between the two settings, supporting the comparability between the VR shopping experience and the experience in the physical supermarket. The VR supermarket can therefore be a valid tool for studying consumer food choice behaviour in a shopping context. Further results show that explicit price memory is weaker compared to implicit price memory, that even prices are remembered better than odd prices, and that price memory follows the expected pattern in a VR supermarket as well. Finally, exploratory findings indicate that the feeling of physical presence and self-presence is relatively high for this particular VR supermarket, whereas social presence is weaker. I senses’  and is i senses’ , therapy senses’ , and mar senses’ ,7. In te senses’  due to i senses’ ,10. Whil senses’ , presenc senses’ ,12.The stunning accuracy of real-world experiences of VR simulation leads to increasing use in retailing ,14. ThisSeveral factors are linked to the intention–behaviour gap  in consuhttps://www.youtube.com/watch?v=ztCi6otS06k, accessed on 7 June 2022) [Specifically, this study investigates the potential for using a VR supermarket (see introduction video ne 2022)  for mirrne 2022) ,35. TherFrom a research perspective, this study contributes to theory by advancing our understanding of how episodic memory in general and price memory in specific are affected by tasks performed in a virtual vs. physical environment. From a practical perspective, as the large majority of fast-moving consumer goods (FMCG) fail on the market, food practitioners may benefit from cost-effective possibilities for testing their products in a realistic environment before they are launched. In this environment, prototypes do not need to be developed before showing the product in a competitive store environment ,22.VR supermarkets have been used for investigating, for instance, consumer attitudinal and purchase behaviour related to brands ,8,22 andis ‘an illusion of “being there” in a computer-mediated environment’ [One of the key features of VR is the feeling of presence that participants can experience compared to traditional experimental settings using text and/or pictures ,40,41,42ronment’ ,43.The feeling of presence is determined by the level of immersion  and interactivity  ,7,32,42.Several studies on VR supermarkets do not provide the possibility to interact with the products but show the products on a screen for consumers to look at , which hAcknowledging the importance of creating a feeling of presence when studying consumer behaviour in VR, technology in the form of head-mounted displays with handheld controllers is argued to be the most typical example of a VR technology being able to create both a high level of immersion and interactivity ,14,32,38Price is one of the most important attributes of consumer choices. Based on only two product categories, consumers tend to form a store price image , which iAn overview of the data collection procedure appears in The first questions addressed the participants’ price recall and price recognition (for two randomly selected products of the three). For the VR supermarket setting, the price memory questions were followed by questions on the feeling of presence in the VR setting.The HP Reverb G2 Omnicept Edition headset was used in the VR supermarket setting. This high-resolution headset allows 114 degrees of viewing at 2160 × 2160 pixels per eye with a refresh rate of 90 Hz. The supermarket setting  was devephysical = 32 ranging from 18 to 82 years, meanVR = 26 ranging from 18 to 79 years, t-valueage = 2.31, p < 0.05) and gender , with a fair spread in distribution of age and gender across the two settings. The participants in the physical supermarket setting (n = 50) were recruited in a large shopping centre in Aarhus, Denmark, close to the university laboratory, in front of a large, well-known Danish supermarket. Potential participants were approached by the researchers and invited to participate in a study on purchase behaviour. In the VR supermarket setting, participants (n = 52) were recruited from a participant pool related to a university laboratory. The participant pool consists of students and persons from other demographics recruited at local fairs and festivals. Participants could sign up for different time slots, and data were collected in the laboratory. Researchers instructed participants on how to use the headset, and each of them were given a tutorial in the VR setting before the actual study took place. The tutorial trained the participants in moving around the store and using the handheld controllers for picking up, rotating, and purchasing products. To avoid biased results, the price was mentioned in neither of the settings in the information to participants. In both settings, the data collection took place at different times of day , during both weekdays and weekends.Within each setting, the final pool of participants varied in age . All constructs were treated as latent constructs and measured with multiple items on a 5-point Likert scale based on Makransky, Lilleholt and Aaby . PhysicaOverall, participants display a relatively low explicit price memory across product categories and store formats. The average error was 19% in the VR supermarket and 24% in the physical supermarket. t-test was conducted to compare the deviations  between the actual price, and the individual price recalls for each product category between the physical and the VR supermarket setting. The results are insignificant . This implies no difference in the participant’s ability to recall prices between the store formats for the three product categories. Moreover, it indicates a relatively low explicit price memory for pasta and pizza sauce, whereas this is higher for the chocolate product category, which was even-priced and on sale.An independent sampled t-test was conducted to compare the participant’s ability to recognise prices for the products (pizza and pasta) between the physical and VR supermarket setting. Since the three possible answers were −10% of the actual price, actual price, and +10% of actual price) the dependent (recognition) variable was treated as numeric. The results are insignificant . This implies that there is no difference in the participants’ ability to recognise prices between the two store formats for the two product categories.Again, an independent sampled A confirmatory factor analysis (CFA) based on the maximum likelihood estimator  was condThe descriptive statistics  show thaThe main goal of this study was to compare shopping experiences in a physical and a VR supermarket by identifying differences in consumers explicit and implicit price memory. The objective was twofold; (1) to contribute to the academic literature on behavioural pricing and reference price, and (2) to validate a VR supermarket for research purposes. We, therefore, conducted a quasi-experiment where participants were asked to shop for products in three food product categories in either the VR supermarket or the physical supermarket setting. In addition, presence was measured to account for participants’ immersion and interactivity in the VR setting.substitute perceived reality [The results show that consumers’ price memory does not differ across the store formats. This finding might be surprising since VR supermarkets are typically smaller and consist of fewer products and shelves , which i reality . That saOverall, our results lend support to previous research on price memory. Explicit price memory is weaker than implicit price memory, and even prices are remembered better than odd prices, including in a VR supermarket. Overall, these findings align with Fang, Nayga Jr., West, Bazzani, Yang, Lok, Levy and Snell) in that the high-immersion VR experience should reduce hypothetical bias .Our research presents positive findings regarding the feeling of presence when consumers are shopping in the virtual supermarket, which aligns with the suggestion of using a head-mounted display together with handheld controllers as a tool supporting the feeling of presence based on immersion and interactivity ,38. ThisPhysical presence, which reflects the participant’s experience of the physical surroundings, is relatively high, indicating that the level of immersion is good. While most VR-based research in consumer behaviour uses environments with lower levels of immersion ,32, our Finally, whereas the feeling of physical presence and self-presence seems to be at satisfactory levels, indicating the overall feeling of “being there”, the results show that the feeling of social presence, which is the participants’ experience of the social actors in the VR environment, is relatively low compared to the two other presence constructs. Our VR supermarket did have a salesperson and other customers in the form of avatars in the store , but parThis study contributes to the emerging stream of research on VR shopping as it validates the chosen VR supermarket as a research tool by studying the influence of the food shopping setting on consumer price memory. Specifically, both implicit and explicit price memory in the physical supermarket is well reflected in the VR supermarket, suggesting comparable shopping experiences across settings. Moreover, the exploratory results on perceived presence indicate a satisfactory level of both physical and self-presence, whereas social presence is weaker. Overall, the study supports the use of this highly immersive and interactive VR supermarket for future research on consumers in-store shopping behaviour for food products.This study validates this VR supermarket for research purposes. Despite positive results on the comparability between the VR and the physical setting on the price memory and perceived presence, validation studies on other factors, such as mode of interaction, movement, and range of product categories influencing consumer shopping behaviour should be considered. Although existing studies show promising results of using VR in food and retail, the specific technologies must always be validated .Moreover, the validity of a VR supermarket may depend on the specific products under investigation . For somRegarding the sampling, the data shows a fair spread of age and gender across the two settings, which supports the validity of the results. Yet, participants in the VR setting were significantly younger compared to the physical supermarket setting. This is a disadvantage of the chosen quasi-experimental design, which was intended to capture least bias in shopping behaviour by observing shoppers in their physical supermarket and lab participants in the VR setting. We assume memory processes for healthy adults to work similarly, irrespective of age, and can draw valid inferences from this study. However, future research could consider other individual characteristics which may influence consumer shopping behaviour related to, for instance, socioeconomic status or cultural differences . AnotherFocusing on the construct of presence, a validated scale was used  to captuFinally, the social presence validity needs to be explored further. This study did not focus on social interaction, and despite simulating other customers and staff in the VR supermarket , partici