Training Physicians to Recognize and Diagnose Rare Diseases Using an Online Serious Game

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Here, we developed a novel evidence-based online serious game about the differential diagnosis of thrombotic microangiopathies, which encompass a group of life-threatening conditions for which early recognition is critical for appropriate management. Methods An online serious game was developed in which participants were given a fixed amount of time to diagnose three virtual patient cases with rare diseases. Two versions were created, a 45-minute version (three cases) and a 15-min version (one case). A cross-sectional, observational study of the serious game was conducted online from October 2022 to April 2024. Participants included physicians and medical students who accessed the online serious game. The main outcomes included participant accessibility, satisfaction, and perceived change in knowledge of thrombotic microangiopathies. Results Participants who accessed the serious game were from 45 countries (n = 926) and chiefly from Europe (87%) followed by the U.S. & Canada (6%). Participants’ medical experience ranged from medical students or graduates (32%) to physicians with ≥ 15 years of experience (17%). At least 8 medical specialties accessed the serious game. Out of 926 participants, 716 tried to diagnose a patient case and 597 completed the serious game. Ninety-three percent (179/193) of participants answering a post-game question reported an improved or substantially improved knowledge of these rare diseases. The mean likelihood of recommending the serious game to a colleague was 8.1/10. Conclusions In this study, an online evidence-based serious game was widely accessed and improved the knowledge of a diverse group of physicians. Online serious games offer potential to train physicians to recognize rare diseases. Additional evidence from other diseases could further support and expand the use of this medium. Clinical trial number: Not applicable Education Gamification Experiential learning Patient cases Rare disease thrombotic thrombocytopenic purpura hemolytic uremic syndrome thrombotic microangiopathies Figures Figure 1 Figure 2 Introduction Rare diseases are defined as those affecting < 5 in 10,000 in Europe [ 1 ] and 60 million people in Europe and the U.S. [ 1 , 2 ]. Rapid recognition, diagnosis, and treatment are critical, especially for life-threatening rare diseases which may sometimes present with atypical and non-specific symptoms [ 3 ]. One example of such rare diseases are thrombotic microangiopathies (TMAs), a term that encompasses a heterogeneous group of disorders with different etiologies that affect the microcirculation and cause life-threatening complications [ 4 ]. Clinically, TMAs are characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia, and organ damage (acute kidney injury, neurological or gastro-intestinal signs and symptoms). Therefore rapid and accurate differential diagnosis is needed in order to improve outcomes [ 4 – 6 ]. One of the causes of TMAs is thrombotic thrombocytopenic purpura (TTP), which has a prevalence of around 10 cases/million with an estimated annual incidence of 1 case/million [ 7 ], and a mortality rate of 90% if untreated [ 8 , 9 ]. It is critical to understand the differential diagnosis between TTP and other TMAs, such as atypical hemolytic uremic syndrome (aHUS), given its different treatment approach and follow-up [ 7 ]. Subsequently, raising awareness for TMAs has been identified as an important need to expedite accurate diagnosis and treatment initiation [ 6 , 10 – 12 ]. Serious games, which are games designed for educational purposes, may offer a digital medium to expose physicians to TMAs and other rare diseases [ 13 , 14 ]. Serious games are built on the concept of experiential learning, which is particularly common in medical education [ 13 , 15 – 19 ]. Experiential learning is considered especially valuable when making decisions under stress [ 20 ]. This is due to the postulate that experience-based knowledge drives clinical decision-making in urgent situations, and may support more rapid decisions [ 20 ]. This may be uniquely important for novices, who self-report ‘limited exposure to clinical situations’ and ‘time limitations’ as important barriers to decision-making [ 21 ]. Serious games can thereby provide an enjoyable and safe, virtual environment to obtain experience with unfamiliar and/or challenging medical cases. Therefore, an evidence-based serious game was co-created by the authors to improve physician knowledge of and familiarity with the differential diagnosis of TMAs. The objective of this study was to test the accessibility, feasibility, satisfaction, and educational value of a serious game in a cross-sectional, observational, online study of healthcare professionals. Methods Study design This study was an international, cross-sectional study conducted online from October 25, 2022 to March 31, 2024. A multi-channel approach was used to recruit participants. This included (1) a digital launch of the serious game by Sanofi Belgium (2) social media dissemination and (3) promotion in hospitals and during international conferences. The serious game was launched in Belgium on October 25, 2022, and subsequently promoted in other European countries in phases with the first international expansion on April 11, 2023 (Sweden and Finland). Accordingly, the data cut-off for this study was approximately 1-year following international expansion. Country-specific launch dates can be found in Supplementary Table 1, Additional File 1. A congress version was also created for in person attendees at conferences. No data from this version is displayed in this manuscript. However, it was launched on 03-Feb-2023. Participants could access the serious game via a landing page ( https://www.go-doctor.eu/ ). All data collected were anonymous and analyzed in aggregate. Participants were informed that cookies were stored to collect their anonymized data associated with the use of the serious game. Details on terms of use and privacy were included in the serious game, aligned with GDPR requirements. Participants Participants of the serious game were included in the study. Inclusion criteria were as follows: they visited the serious game online from October 25, 2022 to March 31, 2024, attested to being a healthcare professional, and selected a patient case. For each participant, the following characteristics were collected anonymously: country, medical specialty, and experience level (> 15 years, 10–15 years, 3–5 years, 1–3 years, intern/resident, medical student or graduate). To assess how participants interacted with the serious game, some definitions were considered: participant, active participant, and participant who completed the serious game. A participant selected a patient case and initiated the timer. An active participant attempted to diagnose at least one patient case. A participant who completed the serious game reached timer 00:00 or correctly diagnosed (all) the patient case(s). See more details about the user flow and participant funnel in Supplementary Table 2, Additional File 2 and Supplementary Fig. 1, Additional File 3. Intervention The serious game was co-created using the SERES™ framework [ 14 ] and leveraging the expertise of a multi-disciplinary team of physicians with experience in diagnosing and treating primary and secondary TMAs (KC, DD, CL, JM). The objective of the serious game was to diagnose patient case(s) accurately and within a limited time frame in an emergency room setting (Fig. 1). To gamify this concept, an emergency room was custom-drawn, and a user interface was developed, which allowed participants to perform numerous actions to aid them in their diagnosis, such as: anamnesis, physical examination, requesting lab and diagnostic tests, and requesting advice to specialists who offer hints. Participants could select as many diagnoses as they wished from a list of over 40 options. This design was selected to resemble real life, including the time pressure of triaging, collaborating with colleagues, requesting and awaiting test results, and diagnosing patients. For example, time pressures included a digital clock on a set timer, lab and imaging tests that required time, and multiple patients. Feedback was provided to participants at several points during the serious game. In particular, the feedback included text (incorrect vs correct diagnosis), hints from specialists in the game, a post-game case summary via text and figures (downloadable PDF), and a post-game video of physicians explaining each case, including key differentiating factors. Figure 1. User flow & visual examples of the case-based online serious game. (A) User flow and aim of the serious game; (B) Visuals of selecting and exploring a patient case. Three patient cases were developed to train participants to recognize the signs and symptoms of these conditions and differentiate between them. Each case addressed a primary or secondary TMA. Physician co-authors developed the content for the patient cases and provided feedback on the serious game. The serious game was developed in English to facilitate international distribution and maximize potential impact. Participants could choose between group or individual play. There was no difference in user experience between the two options. The number of people who participated simultaneously was asked to group participants. The pre-final version of the serious game was distributed by the physician co-authors and validated by their peers. Feedback was collected on numerous topics related to usability, feasibility, and satisfaction. In particular, physicians were asked if a game duration of 45 minutes was too long. Based on preliminary physician feedback, two versions of the serious game were developed – a full version and a short version (see Supplementary Fig. 2, Additional File 4). The full version challenged participants to diagnose 3 patient cases simultaneously in 45 minutes and was launched on October 25, 2022. In contrast, a short version allowed participants to diagnose one or two patient cases separately in 15 minutes and was launched on May 15, 2023. Participants were given the choice between the short and the full version at the start of the serious game. Given the amount of information and case content included, the serious game was optimized for tablet or laptop use. Outcomes The primary study outcomes were accessibility, feasibility, and educational value/satisfaction. All participants, after completing the game, were asked to answer two questions (see Supplementary Fig. 3, Additional File 5). The first post-game question assessed satisfaction by asking participants “How likely are you to recommend this GO Doctor! educational game to another colleague?” using a Likert scale ranging from 0 to 10. The second post-game question assessed the educational value. Participants were asked if their knowledge had improved, substantially improved, or not improved after playing the serious game. Analysis of the subgroup of participants who completed the post-game questions was performed. Accessibility was evaluated using demographic data provided by participants, where they were requested to provide their country/region, specialty, and level of medical experience. Feasibility was assessed in numerous ways. The main outcome measure was based on the number of participants and level of activity (participant vs active participant vs participant completing the serious game) per case. This also included a comparison between participants accessing the short and full versions. The percentage of solved cases was studied to understand the level of perceived difficulty. The user experience was also indirectly evaluated based on participant analytics, such as the number and type of features accessed and the depth of access per case. Subgroup differences were also assessed to determine if there could be barriers restricting certain participants from accessing or engaging with the serious game. Results Participants In total, 926 participants accessed the serious game during the study. The demographics of the participants are displayed in Table 1 . The three most common regions were Belgium (33%), Germany (26%), and Sweden (9%). The most common medical specialty selected was medical student or graduate (32%), ‘other’ (22%; defined as having a specialty different from the available options) and emergency medicine (18%). The top three levels of medical experience were medical student or graduate (32%), more than 15 years of experience (17%) and intern/resident (16%). See Supplementary Table 3, Additional File 6 for more details about the participant funnel and participant breakdown between versions. Table 1 Participant demographics. Characteristic N (%) Unique participants* 926 (100%) Individual 841 (91%) Group 85 (9%) Region 926 (100%) Belgium 309 (33%) Germany 240 (26%) Sweden 86 (9%) United Kingdom 57 (6%) United States 51 (6%) Finland 22 (2%) Italy 18 (2%) Spain 15 (2%) France 8 (1%) Japan 8 (1%) All other countries** 109 (12%) Medical specialty 926 (100%) Medical Student or Graduate 292 (32%) Emergency Room 170 (18%) Internal Medicine–Other Subspecialty 76 (8%) Intensive Care Unit 57 (6%) Nephrology 57 (6%) Hematology 53 (6%) Oncology 19 (2%) Other 202 (22%) Medical experience 926 (100%) > 15 years 162 (17%) 10–15 years 111 (12%) 3–5 years 98 (11%) 1–3 years 115 (12%) Intern/Resident 148 (16%) Medical Student or Graduate 292 (32%) Values from the top 10 countries accessing the serious game are displayed per country. *Total participation is > 1,223 when adding unique participants (841) plus the number of group members (382; calculated as the sum of all replies to the question “With how many players are you playing?”); **See Supplementary Table 4, Additional File 7. Table 1 . Participant demographics. Outcomes Feasibility & accessibility Access to the serious game was broad, with participants from 45 countries across 6 continents (Supplementary Table 4, Additional File 7). Participants accessed most frequently from Europe (87%) and least frequently from South America (< 1%). Three countries, Belgium, Germany, and Sweden, comprised 69% of all participants. Participants could access the serious game and play as an individual or in a group. The number of participants accessing as individuals (841) was greater than those accessing in group sessions (85). The mean number of participants during group sessions was 4.5, and over 382 people played the serious game in a group session. The short version was accessed more frequently than the full version (589 vs 337). Standardizing the participant access based on the number of months since launch, the short version was accessed almost three times more than the full version per month (56 vs 20). Across the full and the short version, 716 participants were considered active (77% of participants). In the end, 597 participants completed the serious game, which was 64% of participants and 83% of active participants. For participants playing the short version, 74% were active and 69% completed the serious game. In contrast for participants playing the full version, 83% and 56% were active and completed the serious game, respectively (Table 2 ). A similar proportion of participants were considered active across all levels of medical experience. Students/graduates had the highest proportion of active participants at nearly 85% (Table 2 ). Notably, in the full version, participants with > 15 years of experience were most active at 89%. Table 2 Active participants as a % of participants. Active participants, n (% of participants) Total Short version Full version Participants 926 (100%) 589 (100%) 337 (100%) Active participants 716 (77%) 436 (74%) 280 (83%) > 15 years 120 (74%) 80 (68%) 40 (89%) 10–15 years 90 (81%) 56 (81%) 34 (81%) 3–5 years 67 (68%) 43 (64%) 24 (77%) 1–3 years 81 (70%) 46 (65%) 35 (80%) Intern/Resident 110 (74%) 72 (73%) 38 (76%) Medical Student or Graduate 248 (85%) 139 (83%) 109 (87%) Participants selected a patient case (timer started). Active participants attempted at least one diagnosis in the serious game. In the full version, the percentage of cases solved by active participants was similar for all three cases, 73%, 74%, and 73% for cases 1 to 3, respectively. Across medical specialties, the proportion of cases solved ranged from 67% (‘other’) to 85% (ICU). Satisfaction & knowledge Participants who completed either version of the serious game reported an average of 8.1/10.0 for the likelihood of recommending the serious game to their colleagues (n = 196). This outcome differed slightly between the full (8.4/10.0) and short versions (7.7/10.0). The post-game knowledge change was similarly positive. Almost 93% of participants reported that their knowledge was ‘substantially improved’ or ‘improved’ after playing the serious game (n = 193; Fig. 2). Participants playing either version reported improvements in knowledge with 97% in the full version and 87% in the short version (Fig. 2). Demographics of the subgroup of participants completing post-game questions are available in Supplementary Table 5, Additional File 8. Figure 2. Reported knowledge change after playing the serious game. Total: all participants (n = 193); Short version participants (n = 77); Full version participants (n = 116). Discussion In this study, we sought to assess the accessibility, feasibility, satisfaction, and educational value of an evidence-based online serious game, training physicians to recognize and diagnose rare diseases with the example of TMAs. The serious game was widely accessed by 926 participants from over 45 countries over a period of 17 months. Beyond the number of participants, there was a strong diversity in both the medical specialty and level of medical experience of participants accessing the serious game. With 24/7 online availability, the serious game supported on-demand access, allowing physicians to engage with the cases at their preferred time and location. The interest across regions, specialties, and levels of experience reiterates the unique potential of employing a digital medium to train physicians. The digital medium did not discourage certain types of physicians from accessing, though, as no subgroup, based on medical experience, comprised < 10% of participants. Moreover, a similar proportion of participants were considered active across all subgroups of medical experience. This suggests that regardless of experience, physicians found the serious game usable and engaging. As also reported in other studies on serious gaming for medical education purposes [ 18 , 22 , 23 ], our study suggests that serious games may be a valuable educational tool for medical schools, as 48% of the participants were medical students or interns/residents. Participants playing the serious game supported its educational value with 93% reporting that their knowledge of these disorders was improved. In addition, participants believed that the serious game could also offer value to their peers, as the mean score to recommend this tool was 8.1/10. The positive feedback may reflect both the preference for the medium and the case-based content. On the latter aspect, it was evident that the cases were challenging, as around 25–30% of active participants were unable to solve ≥ 1 case. These cases appeared to be particularly challenging for certain medical specialities (‘other’, nephrology, and emergency medicine), which reiterates the need for case-based training on rare diseases [ 3 ]. This is further supported by findings from a recent survey in EU5 and U.S. by Rohani-Montez et al. where 32/61 (53%) emergency room physicians reported seeing ≤ 1–2 rare disease patients per year [ 3 ]. Serious games can offer physicians an accessible and engaging medium to safely explore and experience numerous rare disease cases. When given the choice, physicians preferred to play the short version compared to the full version of the serious game, although the proportion of active participants was similar across both versions. This may reflect societal preferences for accessing digital content more rapidly or for shorter durations. It could also reflect the limited time of physicians with busy work schedules. Interestingly, however, both post-game survey questions favored the full version compared to the short version. This suggests that physicians engaging with the serious game preferred to explore all cases. Accessing more cases in the full version may have translated to greater perceived educational value compared to fewer cases in the short version. Interest in playing the serious game as a group was also significant with over 382 physicians playing across 85 group sessions. If all group members were included in participant totals, the number of participants would be > 1,223. Taken together, these results indicate an evidence-based, online serious game is feasible for widely disseminating case-based training on rare diseases. The findings also emphasize the value of offering multiple versions, allowing physicians to tailor their experience depending on preferences. The use of a serious game to support case-based training should also be validated in diseases other than those covered here. Anecdotally, physicians continue to request that new cases be added to the serious game. Given this feedback and the positive outcomes in this study, the co-authors are currently undertaking this expansion. Assessing the educational value and satisfaction of the new cases may also provide further insights. Limitations Based on the study design, several limitations should be acknowledged. For example, knowledge change was self-reported, and no pre-post assessment was performed. Additionally, neither formal assessment of knowledge (i.e., quiz) nor downstream behavior change (i.e., improved diagnosis rates) were assessed. However, including additional outcome measures, such as formal quizzes, could also increase dropout rates. Additionally, a substantial number of users dropped out between accessing the serious game and starting a case. This was unexpected given the limited content preceding the cases –consisting of only 3 demographic questions, avatar selection, and case overview. Possible reasons for these dropouts include curiosity without time to engage in the play, accessing the serious game on a mobile device, or language limitations of the serious game. Beyond comparing different versions of the serious game, no external comparison to (traditional) educational alternatives was performed. However, implementing such a comparison would be challenging and costly at the scale achieved here, especially if paper-based or in-person mediums were included. Although derived from a robust sample, the results from this cohort are mainly from three European countries. These results may not be consistent with a wider, global audience of physicians. Additionally, the serious game was only available in English, which may have prevented access and/or full comprehension from non-native English speakers. Conclusions In this cross-sectional study, an online evidence-based serious game was widely accessed across countries, medical specialty, and medical experience levels. The serious game was believed to improve the rare disease knowledge of this diverse group of physicians. This study highlights the potential of using an online serious game to train physicians to recognize and diagnose rare diseases, such as TMAs. Additional evidence from other diseases could further support and expand the use of this medium. Abbreviations aHUS Atypical hemolytic uremic syndrome EU5 European Union, top 5 countries by population (France, Germany, Italy, Spain, and UK) TMA Thrombotic microangiopathy TTP Thrombocytopenic purpura U.S. United States of America Declarations Ethics approval and consent to participate This study was considered exempt from review and informed consent as no personal/medical data of participants was collected and the aim was a satisfaction survey of physicians. This was determined by the Ethics Committee of Cliniques Universitaires Saint-Luc. Consent for publication Not applicable Availability of data and materials Key cohort-level data are included in the manuscript and supplemental materials. The primary datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests AS and CM are employees of Sanofi Belgium. CB and ML are consultants or employees of MindBytes. KJC reports consultancy for Amgen, Alexion Pharmaceuticals, Astellas, Fresenius Kabi, GSK, and Sanofi; and speaker's fee for AstraZeneca and Vifor Pharma. DD reports consultancy for Atara Biotherapeutics, Incyte, Sanofi, Kite, Pierre Fabre, and Takeda. CL reports consultancy for Amgen, Bayer, CSL Behring, LFB, Octapharma, Roche, Sanofi and Sobi. JM reports research funding from AstraZeneca, AstraZeneca/Alexion Pharmaceuticals; consultancy fees from AstraZeneca, AstraZeneca/Alexion Pharmaceuticals, Bayer, GlaxoSmithKline, Sanofi Genzyme, Versantis, CSL Vifor; speaker honoraria from AstraZeneca/Alexion Pharmaceuticals, Baxter HealthCare and Fresenius Medical Care; JM is also a member of the College for Orphan Drugs/Rare Diseases at the National Institute for Health and Disability Insurance. Funding This work was funded by Sanofi Belgium. Funding was provided to support serious game development, study design, data collection, analysis, and interpretation, and manuscript writing and submission costs. Author’s Contributions The serious game was co-created by all authors (AS, CB, KJC, DD, CL, ML, JM, CM). All authors contributed to the study conception and design. The first draft of the manuscript was written by CB and ML and all authors commented on subsequent versions of the manuscript. All authors read and approved the final manuscript. Acknowledgments We would like to express our deepest gratitude to Anne-Sophie Depuydt and the full Belgian team for their invaluable support throughout this manuscript & project. Their insights, feedback, and help were instrumental in shaping this project. We also want to thank Mohammad Abdelgawwad and Ana Paula Marques for the smooth collaboration and continuous support. References European Commission. RARE a major unmet medical need. 2017. Epub ahead of print 2017. 10.2777/76751 Dicken J. Rare Diseases: Although Limited, Available Evidence Suggests Medical and Other Costs Can Be Substantial. , https://www.gao.gov/products/gao-22-104235 (2021). Rohani-Montez SC, Bomberger J, Zhang C, et al. Educational needs in diagnosing rare diseases: A multinational, multispecialty clinician survey. Genet Med Open. 2023;1:100808. Werion A, Storms P, Zizi Y, et al. Epidemiology, Outcomes, and Complement Gene Variants in Secondary Thrombotic Microangiopathies. Clin J Am Soc Nephrol. 2023;18:881–91. Scully M, Rayment R, Clark A, et al. A British Society for Haematology Guideline: Diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies. Br J Haematol. 2023;203:546–63. McFarlane PA, Bitzan M, Broome C et al. Making the Correct Diagnosis in Thrombotic Microangiopathy: A Narrative Review. Can J Kidney Heal Dis; 8. Epub ahead of print 2021. 10.1177/20543581211008707 Joly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129:2836–46. Azoulay E, Bauer PR, Mariotte E, et al. Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura. Intensive Care Med. 2019;45:1518–39. Kessler CS, Khan BA, Lai-Miller K. Thrombotic thrombocytopenic purpura: A hematological emergency. J Emerg Med. 2012;43:538–44. Tran MH, Patel S, Desai S, et al. Thrombotic microangiopathy - The importance of a multidisciplinary approach. Curr Opin Nephrol Hypertens. 2024;33:247–56. Bull TP, McCulloch R, Nicolson PLR, et al. Diagnostic uncertainty presented barriers to the timely management of acute thrombotic thrombocytopenic purpura in the United Kingdom between 2014 and 2019. J Thromb Haemost. 2022;20:1428–36. Murphy M. Thrombotic Microangiopathy Team-Based Learning Module for Second-Year Medical Students. MedEdPORTAL J Teach Learn Resour. 2017;13:10540. Gentry SV, Gauthier A, L’Estrade Ehrstrom B, et al. Serious Gaming and Gamification Education in Health Professions: Systematic Review. J Med Internet Res. 2019;21:e12994. Verschueren S, Buffel C, Vander Stichele G. Developing theory-driven, evidence-based serious games for health: Framework based on research community insights. JMIR serious games. 2019;21:1–16. Prashant A, Devegowda D, Vishwanath P, et al. Impact of experiential learning among medical undergraduates: A randomized controlled trial. J Educ Health Promot. 2020;9:306. Graafland M, Dankbaar M, Mert A, et al. How to Systematically Assess Serious Games Applied to Health Care. JMIR Serious Games. 2014;2:e11. Yardley S, Teunissen PW, Dornan T. Experiential learning: Transforming theory into practice. Med Teach. 2012;34:161–4. Xu M, Luo Y, Zhang Y et al. Game-based learning in medical education. Front Public Heal 2023; 2017. Cook NF, McAloon T, O’Neill P, et al. Impact of a web based interactive simulation game (PULSE) on nursing students’ experience and performance in life support training - A pilot study. Nurse Educ Today. 2012;32:714–20. Gutnik LA, Hakimzada AF, Yoskowitz NA, et al. The role of emotion in decision-making: A cognitive neuroeconomic approach towards understanding sexual risk behavior. J Biomed Inf. 2006;39:720–36. Szalai C, Herbstreit S, Novosadova K, et al. Learning by doing: To explore the influence of Simulation on Clinical Decision-Making Approaches on Final Year Medical Students at the University of Duisburg-Essen. Ger MedEdPublish. 2021;10:1–13. Aksoy ME, Sayali ME. Serious Gaming as an Additional Learning Tool for Medical Education. Int J Educ Technol Learn. 2019;5:52. Tubelo RA, Portella FF, Gelain MA, et al. Serious game is an effective learning method for primary health care education of medical students: A randomized controlled trial. Int J Med Inf. 2019;130:103944. Additional Declarations Competing interest reported. AS and CM are employees of Sanofi Belgium. CB and ML are consultants or employees of MindBytes. KJC reports consultancy for Amgen, Alexion Pharmaceuticals, Astellas, Fresenius Kabi, GSK, and Sanofi; and speaker's fee for AstraZeneca and Vifor Pharma. DD reports consultancy for Atara Biotherapeutics, Incyte, Sanofi, Kite, Pierre Fabre, and Takeda. CL reports consultancy for Amgen, Bayer, CSL Behring, LFB, Octapharma, Roche, Sanofi and Sobi. JM reports research funding from AstraZeneca, AstraZeneca/Alexion Pharmaceuticals; consultancy fees from AstraZeneca, AstraZeneca/Alexion Pharmaceuticals, Bayer, GlaxoSmithKline, Sanofi Genzyme, Versantis, CSL Vifor; speaker honoraria from AstraZeneca/Alexion Pharmaceuticals, Baxter HealthCare and Fresenius Medical Care; JM is also a member of the College for Orphan Drugs/Rare Diseases at the National Institute for Health and Disability Insurance. Supplementary Files AdditionalFile1.pdf AdditionalFile2.pdf AdditionalFile3.pdf AdditionalFile4.pdf AdditionalFile5.pdf AdditionalFile6.pdf AdditionalFile7.pdf AdditionalFile8.pdf Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 15 Oct, 2024 Editor assigned by journal 14 Oct, 2024 Submission checks completed at journal 12 Oct, 2024 First submitted to journal 23 Sep, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5139843","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":367387852,"identity":"05094e57-3b84-4b1f-b2db-3fd67b360cd6","order_by":0,"name":"An-Sofie Spans","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEUlEQVRIie2PsUrEMBjHv6OQKSVrjkDvCYQehVPwaF8lodCpqKOTRoQ+Q8WX0MU55cDNcw30hnuEiMuBHUx7Ijg05yiY3xD4wv+XfH8Aj+cPggACA0sKQFQ/L4dbwx0KsRaFwip0iBX9MaldylT2H/VBOsyrveJaLG4lsnucREDD5v2ie83I/W0jt5BGR3JE2ajgreY0AbLO2V3VinrzLCSHPFmoEUWfGxbuqJBQxiyULQddHm85KPE0omSaA8OcXlsl+cDdOpvpci5dSvylcIBywTBSk4dfKGhqu8wrelachlUuHnVhu8SuLjwwhl/NCHlZtbhLs0jnzc3uMo3GlG8Q4B9PHYjvwYcjHo/H8z/5BE2NW7GNyUngAAAAAElFTkSuQmCC","orcid":"","institution":"Sanofi","correspondingAuthor":true,"prefix":"","firstName":"An-Sofie","middleName":"","lastName":"Spans","suffix":""},{"id":367387853,"identity":"adafdf0d-8bbd-48ee-a0fa-d66a2f507d54","order_by":1,"name":"Connor Buffel","email":"","orcid":"","institution":"MindBytes","correspondingAuthor":false,"prefix":"","firstName":"Connor","middleName":"","lastName":"Buffel","suffix":""},{"id":367387854,"identity":"9fe6017d-1aef-4614-b9ec-602622175676","order_by":2,"name":"Kathleen J Claes","email":"","orcid":"","institution":"UZ Leuven","correspondingAuthor":false,"prefix":"","firstName":"Kathleen","middleName":"J","lastName":"Claes","suffix":""},{"id":367387855,"identity":"16a6d8bf-7955-4470-94e0-b7842801e04d","order_by":3,"name":"Daan Dierickx","email":"","orcid":"","institution":"University Hospitals Leuven","correspondingAuthor":false,"prefix":"","firstName":"Daan","middleName":"","lastName":"Dierickx","suffix":""},{"id":367387856,"identity":"dae5ffdd-8931-47eb-ad49-38b1593793bc","order_by":4,"name":"Catherine Lambert","email":"","orcid":"","institution":"Cliniques Universitaires Saint-Luc","correspondingAuthor":false,"prefix":"","firstName":"Catherine","middleName":"","lastName":"Lambert","suffix":""},{"id":367387857,"identity":"b891ec52-ba77-4750-b6d7-1e0f5187cdee","order_by":5,"name":"Michelle Luypaert","email":"","orcid":"","institution":"MindBytes","correspondingAuthor":false,"prefix":"","firstName":"Michelle","middleName":"","lastName":"Luypaert","suffix":""},{"id":367387858,"identity":"e6b10777-b579-417b-84a6-3108e1adb7cd","order_by":6,"name":"Johann Morelle","email":"","orcid":"","institution":"University Hospitals Namur (CHU UCL Namur)","correspondingAuthor":false,"prefix":"","firstName":"Johann","middleName":"","lastName":"Morelle","suffix":""},{"id":367387859,"identity":"e44886a1-80a2-4d6f-8c76-3c224286172f","order_by":7,"name":"Chantal Maertens","email":"","orcid":"","institution":"Sanofi","correspondingAuthor":false,"prefix":"","firstName":"Chantal","middleName":"","lastName":"Maertens","suffix":""}],"badges":[],"createdAt":"2024-09-23 18:23:33","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5139843/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5139843/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":69362357,"identity":"b9de85c4-a1c1-4b01-a24a-e42d1e0a0bde","added_by":"auto","created_at":"2024-11-19 14:31:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":477836,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eUser flow \u0026amp; visual examples of the case-based online serious game.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(A) User flow and aim of the serious game; (B) Visuals of selecting and exploring a patient case.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree patient cases were developed to train participants to recognize the signs and symptoms of these conditions and differentiate between them. Each case addressed a primary or secondary TMA. Physician co-authors developed the content for the patient cases and provided feedback on the serious game. The serious game was developed in English to facilitate international distribution and maximize potential impact. Participants could choose between group or individual play. There was no difference in user experience between the two options. The number of people who participated simultaneously was asked to group participants.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5139843/v1/4590962aae62907d86242eb2.png"},{"id":69362353,"identity":"2545950f-9622-4656-bb83-8c666c738083","added_by":"auto","created_at":"2024-11-19 14:31:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":104995,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eReported knowledge change after playing the serious game.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTotal: all participants (n=193); Short version participants (n=77); Full version participants (n=116).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5139843/v1/0f8ab73166d5f8beaf588bfd.png"},{"id":69363982,"identity":"1a3531fd-e4d9-4918-b59c-3d48ee8fe630","added_by":"auto","created_at":"2024-11-19 14:47:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1375035,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5139843/v1/c9102722-2fd4-4079-bbe8-8e9462578699.pdf"},{"id":69363980,"identity":"a35814d3-306e-4680-9d01-b16a3e990c36","added_by":"auto","created_at":"2024-11-19 14:47:12","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":136326,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5139843/v1/9b415e7404071bca9f583fea.pdf"},{"id":69362354,"identity":"b1fac359-0b1b-4156-808c-8dac114bea58","added_by":"auto","created_at":"2024-11-19 14:31:12","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":135865,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5139843/v1/b53ee3b0eb9ed3e3fe351004.pdf"},{"id":69363393,"identity":"11f581d7-677a-479d-b8f5-5fe6aae47a84","added_by":"auto","created_at":"2024-11-19 14:39:12","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":169568,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile3.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5139843/v1/fe09054f755eaa14e88ed460.pdf"},{"id":69362362,"identity":"3133d17f-22f5-49b8-bfac-302ceba26aca","added_by":"auto","created_at":"2024-11-19 14:31:12","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":293272,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile4.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5139843/v1/9bb0d0342f1a3e1483e1e28e.pdf"},{"id":69363981,"identity":"9bfe1ff9-e9d4-4e05-9ed0-740ca55908dd","added_by":"auto","created_at":"2024-11-19 14:47:12","extension":"pdf","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":248476,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile5.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5139843/v1/1252318cdd26791630441bcb.pdf"},{"id":69362359,"identity":"30650cf0-0232-4266-aaa8-3f0c3fad92ee","added_by":"auto","created_at":"2024-11-19 14:31:12","extension":"pdf","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":144430,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile6.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5139843/v1/5e161e45626c0df74fd844e0.pdf"},{"id":69363395,"identity":"0918d3dc-1ffd-46a5-ad3c-e1e1318d10f5","added_by":"auto","created_at":"2024-11-19 14:39:12","extension":"pdf","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":160546,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile7.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5139843/v1/79fa50569385f1c3f3ed2ad3.pdf"},{"id":69362355,"identity":"fd056110-cd20-441b-a747-edf0896d1b69","added_by":"auto","created_at":"2024-11-19 14:31:12","extension":"pdf","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":165400,"visible":true,"origin":"","legend":"","description":"","filename":"AdditionalFile8.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5139843/v1/13009c415b35c05fecfdfe14.pdf"}],"financialInterests":"Competing interest reported. AS and CM are employees of Sanofi Belgium. CB and ML are consultants or employees of MindBytes. KJC reports consultancy for Amgen, Alexion Pharmaceuticals, Astellas, Fresenius Kabi, GSK, and Sanofi; and speaker's fee for AstraZeneca and Vifor Pharma. DD reports consultancy for Atara Biotherapeutics, Incyte, Sanofi, Kite, Pierre Fabre, and Takeda. CL reports consultancy for Amgen, Bayer, CSL Behring, LFB, Octapharma, Roche, Sanofi and Sobi. JM reports research funding from AstraZeneca, AstraZeneca/Alexion Pharmaceuticals; consultancy fees from AstraZeneca, AstraZeneca/Alexion Pharmaceuticals, Bayer, GlaxoSmithKline, Sanofi Genzyme, Versantis, CSL Vifor; speaker honoraria from AstraZeneca/Alexion Pharmaceuticals, Baxter HealthCare and Fresenius Medical Care; JM is also a member of the College for Orphan Drugs/Rare Diseases at the National Institute for Health and Disability Insurance.","formattedTitle":"Training Physicians to Recognize and Diagnose Rare Diseases Using an Online Serious Game","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRare diseases are defined as those affecting\u0026thinsp;\u0026lt;\u0026thinsp;5 in 10,000 in Europe [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] and \u0026lt;\u0026thinsp;200,000 people in the U.S [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The number of rare diseases is currently estimated to be more than 6,000\u0026ndash;8,000, affecting\u0026thinsp;\u0026gt;\u0026thinsp;60\u0026nbsp;million people in Europe and the U.S. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Rapid recognition, diagnosis, and treatment are critical, especially for life-threatening rare diseases which may sometimes present with atypical and non-specific symptoms [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOne example of such rare diseases are thrombotic microangiopathies (TMAs), a term that encompasses a heterogeneous group of disorders with different etiologies that affect the microcirculation and cause life-threatening complications [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Clinically, TMAs are characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia, and organ damage (acute kidney injury, neurological or gastro-intestinal signs and symptoms). Therefore rapid and accurate differential diagnosis is needed in order to improve outcomes [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. One of the causes of TMAs is thrombotic thrombocytopenic purpura (TTP), which has a prevalence of around 10 cases/million with an estimated annual incidence of 1 case/million [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and a mortality rate of 90% if untreated [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. It is critical to understand the differential diagnosis between TTP and other TMAs, such as atypical hemolytic uremic syndrome (aHUS), given its different treatment approach and follow-up [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSubsequently, raising awareness for TMAs has been identified as an important need to expedite accurate diagnosis and treatment initiation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Serious games, which are games designed for educational purposes, may offer a digital medium to expose physicians to TMAs and other rare diseases [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Serious games are built on the concept of experiential learning, which is particularly common in medical education [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16 CR17 CR18\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Experiential learning is considered especially valuable when making decisions under stress [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This is due to the postulate that experience-based knowledge drives clinical decision-making in urgent situations, and may support more rapid decisions [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This may be uniquely important for novices, who self-report \u0026lsquo;limited exposure to clinical situations\u0026rsquo; and \u0026lsquo;time limitations\u0026rsquo; as important barriers to decision-making [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Serious games can thereby provide an enjoyable and safe, virtual environment to obtain experience with unfamiliar and/or challenging medical cases.\u003c/p\u003e \u003cp\u003eTherefore, an evidence-based serious game was co-created by the authors to improve physician knowledge of and familiarity with the differential diagnosis of TMAs. The objective of this study was to test the accessibility, feasibility, satisfaction, and educational value of a serious game in a cross-sectional, observational, online study of healthcare professionals.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eStudy design\u003c/p\u003e \u003cp\u003eThis study was an international, cross-sectional study conducted online from October 25, 2022 to March 31, 2024. A multi-channel approach was used to recruit participants. This included (1) a digital launch of the serious game by Sanofi Belgium (2) social media dissemination and (3) promotion in hospitals and during international conferences. The serious game was launched in Belgium on October 25, 2022, and subsequently promoted in other European countries in phases with the first international expansion on April 11, 2023 (Sweden and Finland). Accordingly, the data cut-off for this study was approximately 1-year following international expansion. Country-specific launch dates can be found in Supplementary Table\u0026nbsp;1, Additional File 1. A congress version was also created for in person attendees at conferences. No data from this version is displayed in this manuscript. However, it was launched on 03-Feb-2023.\u003c/p\u003e \u003cp\u003eParticipants could access the serious game via a landing page (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.go-doctor.eu/\u003c/span\u003e\u003cspan address=\"https://www.go-doctor.eu/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). All data collected were anonymous and analyzed in aggregate. Participants were informed that cookies were stored to collect their anonymized data associated with the use of the serious game. Details on terms of use and privacy were included in the serious game, aligned with GDPR requirements.\u003c/p\u003e \u003cp\u003eParticipants\u003c/p\u003e \u003cp\u003eParticipants of the serious game were included in the study. Inclusion criteria were as follows: they visited the serious game online from October 25, 2022 to March 31, 2024, attested to being a healthcare professional, and selected a patient case. For each participant, the following characteristics were collected anonymously: country, medical specialty, and experience level (\u0026gt;\u0026thinsp;15 years, 10\u0026ndash;15 years, 3\u0026ndash;5 years, 1\u0026ndash;3 years, intern/resident, medical student or graduate). To assess how participants interacted with the serious game, some definitions were considered: participant, active participant, and participant who completed the serious game. A \u003cem\u003eparticipant\u003c/em\u003e selected a patient case and initiated the timer. An \u003cem\u003eactive participant\u003c/em\u003e attempted to diagnose at least one patient case. A \u003cem\u003eparticipant who completed the serious game\u003c/em\u003e reached timer 00:00 or correctly diagnosed (all) the patient case(s). See more details about the user flow and participant funnel in Supplementary Table\u0026nbsp;2, Additional File 2 and Supplementary Fig.\u0026nbsp;1, Additional File 3.\u003c/p\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003cp\u003eThe serious game was co-created using the SERES\u0026trade; framework [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and leveraging the expertise of a multi-disciplinary team of physicians with experience in diagnosing and treating primary and secondary TMAs (KC, DD, CL, JM). The objective of the serious game was to diagnose patient case(s) accurately and within a limited time frame in an emergency room setting (Fig.\u0026nbsp;1). To gamify this concept, an emergency room was custom-drawn, and a user interface was developed, which allowed participants to perform numerous actions to aid them in their diagnosis, such as: anamnesis, physical examination, requesting lab and diagnostic tests, and requesting advice to specialists who offer hints. Participants could select as many diagnoses as they wished from a list of over 40 options. This design was selected to resemble real life, including the time pressure of triaging, collaborating with colleagues, requesting and awaiting test results, and diagnosing patients. For example, time pressures included a digital clock on a set timer, lab and imaging tests that required time, and multiple patients. Feedback was provided to participants at several points during the serious game. In particular, the feedback included text (incorrect vs correct diagnosis), hints from specialists in the game, a post-game case summary via text and figures (downloadable PDF), and a post-game video of physicians explaining each case, including key differentiating factors.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 1. User flow \u0026amp; visual examples of the case-based online serious game.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003e(A) User flow and aim of the serious game; (B) Visuals of selecting and exploring a patient case.\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThree patient cases were developed to train participants to recognize the signs and symptoms of these conditions and differentiate between them. Each case addressed a primary or secondary TMA. Physician co-authors developed the content for the patient cases and provided feedback on the serious game. The serious game was developed in English to facilitate international distribution and maximize potential impact. Participants could choose between group or individual play. There was no difference in user experience between the two options. The number of people who participated simultaneously was asked to group participants.\u003c/p\u003e \u003cp\u003eThe pre-final version of the serious game was distributed by the physician co-authors and validated by their peers. Feedback was collected on numerous topics related to usability, feasibility, and satisfaction. In particular, physicians were asked if a game duration of 45 minutes was too long. Based on preliminary physician feedback, two versions of the serious game were developed \u0026ndash; a full version and a short version (see Supplementary Fig.\u0026nbsp;2, Additional File 4). The full version challenged participants to diagnose 3 patient cases simultaneously in 45 minutes and was launched on October 25, 2022. In contrast, a short version allowed participants to diagnose one or two patient cases separately in 15 minutes and was launched on May 15, 2023. Participants were given the choice between the short and the full version at the start of the serious game. Given the amount of information and case content included, the serious game was optimized for tablet or laptop use.\u003c/p\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003cp\u003eThe primary study outcomes were accessibility, feasibility, and educational value/satisfaction. All participants, after completing the game, were asked to answer two questions (see Supplementary Fig.\u0026nbsp;3, Additional File 5). The first post-game question assessed satisfaction by asking participants \u0026ldquo;How likely are you to recommend this GO Doctor! educational game to another colleague?\u0026rdquo; using a Likert scale ranging from 0 to 10. The second post-game question assessed the educational value. Participants were asked if their knowledge had improved, substantially improved, or not improved after playing the serious game. Analysis of the subgroup of participants who completed the post-game questions was performed.\u003c/p\u003e \u003cp\u003eAccessibility was evaluated using demographic data provided by participants, where they were requested to provide their country/region, specialty, and level of medical experience.\u003c/p\u003e \u003cp\u003eFeasibility was assessed in numerous ways. The main outcome measure was based on the number of participants and level of activity (participant vs active participant vs participant completing the serious game) per case. This also included a comparison between participants accessing the short and full versions. The percentage of solved cases was studied to understand the level of perceived difficulty. The user experience was also indirectly evaluated based on participant analytics, such as the number and type of features accessed and the depth of access per case.\u003c/p\u003e \u003cp\u003eSubgroup differences were also assessed to determine if there could be barriers restricting certain participants from accessing or engaging with the serious game.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eParticipants\u003c/p\u003e \u003cp\u003eIn total, 926 participants accessed the serious game during the study. The demographics of the participants are displayed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The three most common regions were Belgium (33%), Germany (26%), and Sweden (9%). The most common medical specialty selected was medical student or graduate (32%), \u0026lsquo;other\u0026rsquo; (22%; defined as having a specialty different from the available options) and emergency medicine (18%). The top three levels of medical experience were medical student or graduate (32%), more than 15 years of experience (17%) and intern/resident (16%). See Supplementary Table\u0026nbsp;3, Additional File 6 for more details about the participant funnel and participant breakdown between versions.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eParticipant demographics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnique participants*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e926 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndividual\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e841 (91%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85 (9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e926 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBelgium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e309 (33%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGermany\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e240 (26%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86 (9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited Kingdom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited States\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFinland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll other countries**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e109 (12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical specialty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e926 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical Student or Graduate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e292 (32%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmergency Room\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e170 (18%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInternal Medicine\u0026ndash;Other Subspecialty\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntensive Care Unit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNephrology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOncology\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e202 (22%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical experience\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e926 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;15 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e162 (17%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u0026ndash;15 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e111 (12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u0026ndash;5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98 (11%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e115 (12%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntern/Resident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e148 (16%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical Student or Graduate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e292 (32%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cb\u003eValues from the top 10 countries accessing the serious game are displayed per country. *Total participation is \u0026gt;\u0026thinsp;1,223 when adding unique participants (841) plus the number of group members (382; calculated as the sum of all replies to the question \u0026ldquo;With how many players are you playing?\u0026rdquo;); **See Supplementary Table\u0026nbsp;4, Additional File 7.\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. \u003cb\u003eParticipant demographics.\u003c/b\u003e\u003c/p\u003e \u003cp\u003eOutcomes\u003c/p\u003e \u003cp\u003eFeasibility \u0026amp; accessibility\u003c/p\u003e \u003cp\u003eAccess to the serious game was broad, with participants from 45 countries across 6 continents (Supplementary Table\u0026nbsp;4, Additional File 7). Participants accessed most frequently from Europe (87%) and least frequently from South America (\u0026lt;\u0026thinsp;1%). Three countries, Belgium, Germany, and Sweden, comprised 69% of all participants.\u003c/p\u003e \u003cp\u003eParticipants could access the serious game and play as an individual or in a group. The number of participants accessing as individuals (841) was greater than those accessing in group sessions (85). The mean number of participants during group sessions was 4.5, and over 382 people played the serious game in a group session.\u003c/p\u003e \u003cp\u003eThe short version was accessed more frequently than the full version (589 vs 337). Standardizing the participant access based on the number of months since launch, the short version was accessed almost three times more than the full version per month (56 vs 20).\u003c/p\u003e \u003cp\u003eAcross the full and the short version, 716 participants were considered active (77% of participants). In the end, 597 participants completed the serious game, which was 64% of participants and 83% of active participants. For participants playing the short version, 74% were active and 69% completed the serious game. In contrast for participants playing the full version, 83% and 56% were active and completed the serious game, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). A similar proportion of participants were considered active across all levels of medical experience. Students/graduates had the highest proportion of active participants at nearly 85% (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Notably, in the full version, participants with \u0026gt;\u0026thinsp;15 years of experience were most active at 89%.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eActive participants as a % of participants.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eActive participants, n (% of participants)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eTotal\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eShort version\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003eFull version\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParticipants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e926 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e589 (100%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e337 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActive participants\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e716 (77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e436 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e280 (83%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;15 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e120 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80 (68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (89%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u0026ndash;15 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 (81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56 (81%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34 (81%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u0026ndash;5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67 (68%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (77%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81 (70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35 (80%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntern/Resident\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e110 (74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (73%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38 (76%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedical Student or Graduate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e248 (85%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e139 (83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e109 (87%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eParticipants\u003c/b\u003e \u003cb\u003eselected a patient case (timer started).\u003c/b\u003e \u003cb\u003eActive participants\u003c/b\u003e \u003cb\u003eattempted at least one diagnosis in the serious game.\u003c/b\u003e\u003c/p\u003e \u003cp\u003e In the full version, the percentage of cases solved by active participants was similar for all three cases, 73%, 74%, and 73% for cases 1 to 3, respectively. Across medical specialties, the proportion of cases solved ranged from 67% (\u0026lsquo;other\u0026rsquo;) to 85% (ICU).\u003c/p\u003e \u003cp\u003eSatisfaction \u0026amp; knowledge\u003c/p\u003e \u003cp\u003eParticipants who completed either version of the serious game reported an average of 8.1/10.0 for the likelihood of recommending the serious game to their colleagues (n\u0026thinsp;=\u0026thinsp;196). This outcome differed slightly between the full (8.4/10.0) and short versions (7.7/10.0).\u003c/p\u003e \u003cp\u003eThe post-game knowledge change was similarly positive. Almost 93% of participants reported that their knowledge was \u0026lsquo;substantially improved\u0026rsquo; or \u0026lsquo;improved\u0026rsquo; after playing the serious game (n\u0026thinsp;=\u0026thinsp;193; Fig.\u0026nbsp;2). Participants playing either version reported improvements in knowledge with 97% in the full version and 87% in the short version (Fig.\u0026nbsp;2). Demographics of the subgroup of participants completing post-game questions are available in Supplementary Table\u0026nbsp;5, Additional File 8.\u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 2. Reported knowledge change after playing the serious game.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eTotal: all participants (n\u0026thinsp;=\u0026thinsp;193); Short version participants (n\u0026thinsp;=\u0026thinsp;77); Full version participants (n\u0026thinsp;=\u0026thinsp;116).\u003c/b\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we sought to assess the accessibility, feasibility, satisfaction, and educational value of an evidence-based online serious game, training physicians to recognize and diagnose rare diseases with the example of TMAs. The serious game was widely accessed by 926 participants from over 45 countries over a period of 17 months. Beyond the number of participants, there was a strong diversity in both the medical specialty and level of medical experience of participants accessing the serious game. With 24/7 online availability, the serious game supported on-demand access, allowing physicians to engage with the cases at their preferred time and location. The interest across regions, specialties, and levels of experience reiterates the unique potential of employing a digital medium to train physicians. The digital medium did not discourage certain types of physicians from accessing, though, as no subgroup, based on medical experience, comprised\u0026thinsp;\u0026lt;\u0026thinsp;10% of participants. Moreover, a similar proportion of participants were considered active across all subgroups of medical experience. This suggests that regardless of experience, physicians found the serious game usable and engaging. As also reported in other studies on serious gaming for medical education purposes [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], our study suggests that serious games may be a valuable educational tool for medical schools, as 48% of the participants were medical students or interns/residents.\u003c/p\u003e \u003cp\u003eParticipants playing the serious game supported its educational value with 93% reporting that their knowledge of these disorders was improved. In addition, participants believed that the serious game could also offer value to their peers, as the mean score to recommend this tool was 8.1/10. The positive feedback may reflect both the preference for the medium and the case-based content. On the latter aspect, it was evident that the cases were challenging, as around 25\u0026ndash;30% of active participants were unable to solve\u0026thinsp;\u0026ge;\u0026thinsp;1 case. These cases appeared to be particularly challenging for certain medical specialities (\u0026lsquo;other\u0026rsquo;, nephrology, and emergency medicine), which reiterates the need for case-based training on rare diseases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. This is further supported by findings from a recent survey in EU5 and U.S. by Rohani-Montez et al. where 32/61 (53%) emergency room physicians reported seeing\u0026thinsp;\u0026le;\u0026thinsp;1\u0026ndash;2 rare disease patients per year [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Serious games can offer physicians an accessible and engaging medium to safely explore and experience numerous rare disease cases.\u003c/p\u003e \u003cp\u003eWhen given the choice, physicians preferred to play the short version compared to the full version of the serious game, although the proportion of active participants was similar across both versions. This may reflect societal preferences for accessing digital content more rapidly or for shorter durations. It could also reflect the limited time of physicians with busy work schedules. Interestingly, however, both post-game survey questions favored the full version compared to the short version. This suggests that physicians engaging with the serious game preferred to explore all cases. Accessing more cases in the full version may have translated to greater perceived educational value compared to fewer cases in the short version.\u003c/p\u003e \u003cp\u003eInterest in playing the serious game as a group was also significant with over 382 physicians playing across 85 group sessions. If all group members were included in participant totals, the number of participants would be \u0026gt;\u0026thinsp;1,223.\u003c/p\u003e \u003cp\u003eTaken together, these results indicate an evidence-based, online serious game is feasible for widely disseminating case-based training on rare diseases. The findings also emphasize the value of offering multiple versions, allowing physicians to tailor their experience depending on preferences. The use of a serious game to support case-based training should also be validated in diseases other than those covered here. Anecdotally, physicians continue to request that new cases be added to the serious game. Given this feedback and the positive outcomes in this study, the co-authors are currently undertaking this expansion. Assessing the educational value and satisfaction of the new cases may also provide further insights.\u003c/p\u003e \u003cp\u003eLimitations\u003c/p\u003e \u003cp\u003eBased on the study design, several limitations should be acknowledged. For example, knowledge change was self-reported, and no pre-post assessment was performed. Additionally, neither formal assessment of knowledge (i.e., quiz) nor downstream behavior change (i.e., improved diagnosis rates) were assessed. However, including additional outcome measures, such as formal quizzes, could also increase dropout rates. Additionally, a substantial number of users dropped out between accessing the serious game and starting a case. This was unexpected given the limited content preceding the cases \u0026ndash;consisting of only 3 demographic questions, avatar selection, and case overview. Possible reasons for these dropouts include curiosity without time to engage in the play, accessing the serious game on a mobile device, or language limitations of the serious game.\u003c/p\u003e \u003cp\u003eBeyond comparing different versions of the serious game, no external comparison to (traditional) educational alternatives was performed. However, implementing such a comparison would be challenging and costly at the scale achieved here, especially if paper-based or in-person mediums were included. Although derived from a robust sample, the results from this cohort are mainly from three European countries. These results may not be consistent with a wider, global audience of physicians. Additionally, the serious game was only available in English, which may have prevented access and/or full comprehension from non-native English speakers.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this cross-sectional study, an online evidence-based serious game was widely accessed across countries, medical specialty, and medical experience levels. The serious game was believed to improve the rare disease knowledge of this diverse group of physicians. This study highlights the potential of using an online serious game to train physicians to recognize and diagnose rare diseases, such as TMAs. Additional evidence from other diseases could further support and expand the use of this medium.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eaHUS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAtypical hemolytic uremic syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eEU5\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Union, top 5 countries by population (France, Germany, Italy, Spain, and UK)\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTMA\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThrombotic microangiopathy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTTP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThrombocytopenic purpura\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eU.S.\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eUnited States of America\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis study was considered exempt from review and informed consent as no personal/medical data of participants was collected and the aim was a satisfaction survey of physicians. This was determined by the Ethics Committee of Cliniques Universitaires Saint-Luc.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eKey cohort-level data are included in the manuscript and supplemental materials. The primary datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eAS and CM are employees of Sanofi Belgium. CB and ML are consultants or employees of MindBytes. KJC reports consultancy for Amgen, Alexion Pharmaceuticals, Astellas, Fresenius Kabi, GSK, and Sanofi; and speaker\u0026apos;s fee for AstraZeneca and Vifor Pharma. DD reports consultancy for Atara Biotherapeutics, Incyte, Sanofi, Kite, Pierre Fabre, and Takeda. CL reports consultancy for Amgen, Bayer, CSL Behring, LFB, Octapharma, Roche, Sanofi and Sobi. JM reports research funding from AstraZeneca, AstraZeneca/Alexion Pharmaceuticals; consultancy fees from AstraZeneca, AstraZeneca/Alexion Pharmaceuticals, Bayer, GlaxoSmithKline, Sanofi Genzyme, Versantis, CSL Vifor; speaker honoraria from AstraZeneca/Alexion Pharmaceuticals, Baxter HealthCare and Fresenius Medical Care; JM is also a member of the College for Orphan Drugs/Rare Diseases at the National Institute for Health and Disability Insurance.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis work was funded by Sanofi Belgium. Funding was provided to support serious game development, study design, data collection, analysis, and interpretation, and manuscript writing and submission costs.\u003c/p\u003e\n\u003cp\u003eAuthor\u0026rsquo;s Contributions\u003c/p\u003e\n\u003cp\u003eThe serious game was co-created by all authors (AS, CB, KJC, DD, CL, ML, JM, CM). All authors contributed to the study conception and design. The first draft of the manuscript was written by CB and ML and all authors commented on subsequent versions of the manuscript. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eWe would like to express our deepest gratitude to Anne-Sophie Depuydt and the full Belgian team for their invaluable support throughout this manuscript \u0026amp; project. Their insights, feedback, and help were instrumental in shaping this project. We also want to thank Mohammad Abdelgawwad and Ana Paula Marques for the smooth collaboration and continuous support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEuropean Commission. RARE a major unmet medical need. 2017. Epub ahead of print 2017. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2777/76751\u003c/span\u003e\u003cspan address=\"10.2777/76751\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDicken J. \u003cem\u003eRare Diseases: Although Limited, Available Evidence Suggests Medical and Other Costs Can Be Substantial.\u003c/em\u003e, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.gao.gov/products/gao-22-104235\u003c/span\u003e\u003cspan address=\"https://www.gao.gov/products/gao-22-104235\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRohani-Montez SC, Bomberger J, Zhang C, et al. Educational needs in diagnosing rare diseases: A multinational, multispecialty clinician survey. Genet Med Open. 2023;1:100808.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWerion A, Storms P, Zizi Y, et al. Epidemiology, Outcomes, and Complement Gene Variants in Secondary Thrombotic Microangiopathies. Clin J Am Soc Nephrol. 2023;18:881\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScully M, Rayment R, Clark A, et al. A British Society for Haematology Guideline: Diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies. Br J Haematol. 2023;203:546\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcFarlane PA, Bitzan M, Broome C et al. Making the Correct Diagnosis in Thrombotic Microangiopathy: A Narrative Review. Can J Kidney Heal Dis; 8. Epub ahead of print 2021. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/20543581211008707\u003c/span\u003e\u003cspan address=\"10.1177/20543581211008707\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJoly BS, Coppo P, Veyradier A. Thrombotic thrombocytopenic purpura. Blood. 2017;129:2836\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAzoulay E, Bauer PR, Mariotte E, et al. Expert statement on the ICU management of patients with thrombotic thrombocytopenic purpura. Intensive Care Med. 2019;45:1518\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKessler CS, Khan BA, Lai-Miller K. Thrombotic thrombocytopenic purpura: A hematological emergency. J Emerg Med. 2012;43:538\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTran MH, Patel S, Desai S, et al. Thrombotic microangiopathy - The importance of a multidisciplinary approach. Curr Opin Nephrol Hypertens. 2024;33:247\u0026ndash;56.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBull TP, McCulloch R, Nicolson PLR, et al. Diagnostic uncertainty presented barriers to the timely management of acute thrombotic thrombocytopenic purpura in the United Kingdom between 2014 and 2019. J Thromb Haemost. 2022;20:1428\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurphy M. Thrombotic Microangiopathy Team-Based Learning Module for Second-Year Medical Students. MedEdPORTAL J Teach Learn Resour. 2017;13:10540.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGentry SV, Gauthier A, L\u0026rsquo;Estrade Ehrstrom B, et al. Serious Gaming and Gamification Education in Health Professions: Systematic Review. J Med Internet Res. 2019;21:e12994.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVerschueren S, Buffel C, Vander Stichele G. Developing theory-driven, evidence-based serious games for health: Framework based on research community insights. JMIR serious games. 2019;21:1\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrashant A, Devegowda D, Vishwanath P, et al. Impact of experiential learning among medical undergraduates: A randomized controlled trial. J Educ Health Promot. 2020;9:306.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGraafland M, Dankbaar M, Mert A, et al. How to Systematically Assess Serious Games Applied to Health Care. JMIR Serious Games. 2014;2:e11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYardley S, Teunissen PW, Dornan T. Experiential learning: Transforming theory into practice. Med Teach. 2012;34:161\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu M, Luo Y, Zhang Y et al. Game-based learning in medical education. \u003cem\u003eFront Public Heal\u003c/em\u003e 2023; 2017.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCook NF, McAloon T, O\u0026rsquo;Neill P, et al. Impact of a web based interactive simulation game (PULSE) on nursing students\u0026rsquo; experience and performance in life support training - A pilot study. Nurse Educ Today. 2012;32:714\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGutnik LA, Hakimzada AF, Yoskowitz NA, et al. The role of emotion in decision-making: A cognitive neuroeconomic approach towards understanding sexual risk behavior. J Biomed Inf. 2006;39:720\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSzalai C, Herbstreit S, Novosadova K, et al. Learning by doing: To explore the influence of Simulation on Clinical Decision-Making Approaches on Final Year Medical Students at the University of Duisburg-Essen. Ger MedEdPublish. 2021;10:1\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAksoy ME, Sayali ME. Serious Gaming as an Additional Learning Tool for Medical Education. Int J Educ Technol Learn. 2019;5:52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTubelo RA, Portella FF, Gelain MA, et al. Serious game is an effective learning method for primary health care education of medical students: A randomized controlled trial. Int J Med Inf. 2019;130:103944.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-education","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"meed","sideBox":"Learn more about [BMC Medical Education](http://bmcmededuc.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/meed/default.aspx","title":"BMC Medical Education","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Education, Gamification, Experiential learning, Patient cases, Rare disease, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, thrombotic microangiopathies","lastPublishedDoi":"10.21203/rs.3.rs-5139843/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5139843/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eIncreasing physicians\u0026rsquo; awareness and knowledge of rare diseases may positively impact their ability to recognize and diagnose these conditions timely. Here, we developed a novel evidence-based online serious game about the differential diagnosis of thrombotic microangiopathies, which encompass a group of life-threatening conditions for which early recognition is critical for appropriate management.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eAn online serious game was developed in which participants were given a fixed amount of time to diagnose three virtual patient cases with rare diseases. Two versions were created, a 45-minute version (three cases) and a 15-min version (one case). A cross-sectional, observational study of the serious game was conducted online from October 2022 to April 2024. Participants included physicians and medical students who accessed the online serious game. The main outcomes included participant accessibility, satisfaction, and perceived change in knowledge of thrombotic microangiopathies.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eParticipants who accessed the serious game were from 45 countries (n\u0026thinsp;=\u0026thinsp;926) and chiefly from Europe (87%) followed by the U.S. \u0026amp; Canada (6%). Participants\u0026rsquo; medical experience ranged from medical students or graduates (32%) to physicians with \u0026ge;\u0026thinsp;15 years of experience (17%). At least 8 medical specialties accessed the serious game. Out of 926 participants, 716 tried to diagnose a patient case and 597 completed the serious game. Ninety-three percent (179/193) of participants answering a post-game question reported an improved or substantially improved knowledge of these rare diseases. The mean likelihood of recommending the serious game to a colleague was 8.1/10.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn this study, an online evidence-based serious game was widely accessed and improved the knowledge of a diverse group of physicians. Online serious games offer potential to train physicians to recognize rare diseases. Additional evidence from other diseases could further support and expand the use of this medium.\u003c/p\u003e\u003ch2\u003eClinical trial number:\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e","manuscriptTitle":"Training Physicians to Recognize and Diagnose Rare Diseases Using an Online Serious Game","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-19 14:31:07","doi":"10.21203/rs.3.rs-5139843/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-15T13:52:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-14T04:47:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-12T09:19:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Medical Education","date":"2024-09-23T18:20:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-medical-education","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"meed","sideBox":"Learn more about [BMC Medical Education](http://bmcmededuc.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/meed/default.aspx","title":"BMC Medical Education","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7e7132e9-a248-46cf-a2b7-0a9f1670ec28","owner":[],"postedDate":"November 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-23T05:54:55+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-19 14:31:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5139843","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5139843","identity":"rs-5139843","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}