"Asking for help is a strength"-how to promote undergraduate medical students' teamwork through simulation training and interprofessional faculty.

The ability to team up and safely work in any kind of healthcare team is a critical asset and should be taught early on in medical education. Medical students should be given the chance to "walk the talk" of teamwork by training and reflecting in teams. Our goal was to design, implement and evaluate the feasibility of a simulation-based teamwork training (TeamSIM) for undergraduate medical students that puts generic teamwork skills centerstage. We designed TeamSIM to include 12 learning objectives. For this pre-post, mixed-methods feasibility study, third-year medical students, organized in teams of 11-12 students, participated and observed each other in eight simulations of different clinical situation with varying degrees of complexity (e.g., deteriorating patient in ward; trauma; resuscitation). Guided by an interprofessional clinical faculty with simulation-based instructor training, student teams reflected on their shared experience in structured team debriefings. Using published instruments, we measured (a) students' reactions to TeamSIM and their perceptions of psychological safety via self-report, (b) their ongoing reflections via experience sampling, and (c) their teamwork skills via behavior observation. Ninety four students participated. They reported positive reactions to TeamSIM (M = 5.23, SD = 0.5). Their mean initial reported level of psychological safety was M = 3.8 (SD = 0.4) which rose to M = 4.3 (SD = 0.5) toward the end of the course [T(21) = -2.8, 95% CI -0.78 to-0.12, p = 0.011 (two-tailed)]. We obtained n = 314 headline reflections from the students and n = 95 from the faculty. For the students, the most frequent theme assigned to their headlines involved the concepts taught in the course such as "10 s for 10 min." For the faculty, the most frequent theme assigned to their headlines were reflections on how their simulation session worked for the students. The faculty rated students' teamwork skills higher after the last compared to the first debriefing. Undergraduate medical students can learn crucial teamwork skills in simulations supported by an experienced faculty and with a high degree of psychological safety. Both students and faculty appreciate the learning possibilities of simulation. At the same time, this learning can be challenging, intense and overwhelming. It takes a team to teach teamwork.

How Much Evidence Is Enough? Research Sponsor Experiences Seeking Regulatory Acceptance of Digital Health Technology-Derived Endpoints.

Introduction: Digital health technologies (DHTs) provide opportunities for real-time data collection and assessment of patient function. However, use of DHT-derived endpoints in clinical trials to support medical product labelling claims is limited. Methods: From November 2020 through March 2021, the Clinical Trials Transformation Initiative (CTTI) conducted a qualitative descriptive study using semi-structured interviews with sponsors of clinical trials that used DHT-derived endpoints. We aimed to learn about their experiences, including their interactions with regulators and the challenges they encountered. Using applied thematic analysis, we identified barriers to and recommendations for using DHT-derived endpoints in pivotal trials. Results: Sponsors identified five key challenges to incorporating DHT-derived endpoints in clinical trials. These included (1) a need for additional regulatory clarity specific to DHT-derived endpoints, (2) the official clinical outcome assessment qualification process being impractical for the biopharmaceutical industry, (3) a lack of comparator clinical endpoints, (4) a lack of validated DHTs and algorithms for concepts of interest, and (5) a lack of operational support from DHT vendors. Discussion/Conclusion: CTTI shared the interview findings with the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and during a multi-stakeholder expert meeting. Based on these discussions, we provide several new and revised tools to aid sponsors in using DHT-derived endpoints in pivotal trials to support labelling claims.

Translational longevity medicine: a Swiss perspective in an ageing country.

Breakthroughs in medical research in the last century have led to a significant extension of the human lifespan, resulting in a shift towards an elderly population worldwide. Due to the ongoing progress of global development towards elevated standards of living, this study specifically examines Switzerland as a representative nation to explore the socioeconomic and healthcare ramifications associated with an ageing population, thereby highlighting the tangible impact experienced in this context. Beyond the exhaustion of pension funds and medical budgets, by reviewing the literature and analysing publicly available data, we observe a "Swiss Japanification". Old age is associated with late-life comorbidities and an increasing proportion of time spent in poor health. To address these problems, a paradigm shift in medical practice is needed to improve health rather than respond to existing diseases. Basic ageing research is gaining momentum to be translated into therapeutic interventions and provides machine learning tools driving longevity medicine. We propose that research focus on closing the translational gap between the molecular mechanisms of ageing and a more prevention-based medicine, which would help people age better and prevent late-life chronic diseases.

Machine learning analysis of humoral and cellular responses to SARS-CoV-2 infection in young adults.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces B and T cell responses, contributing to virus neutralization. In a cohort of 2,911 young adults, we identified 65 individuals who had an asymptomatic or mildly symptomatic SARS-CoV-2 infection and characterized their humoral and T cell responses to the Spike (S), Nucleocapsid (N) and Membrane (M) proteins. We found that previous infection induced CD4 T cells that vigorously responded to pools of peptides derived from the S and N proteins. By using statistical and machine learning models, we observed that the T cell response highly correlated with a compound titer of antibodies against the Receptor Binding Domain (RBD), S and N. However, while serum antibodies decayed over time, the cellular phenotype of these individuals remained stable over four months. Our computational analysis demonstrates that in young adults, asymptomatic and paucisymptomatic SARS-CoV-2 infections can induce robust and long-lasting CD4 T cell responses that exhibit slower decays than antibody titers. These observations imply that next-generation COVID-19 vaccines should be designed to induce stronger cellular responses to sustain the generation of potent neutralizing antibodies.

A three-level model for therapeutic drug monitoring of antimicrobials at the site of infection.

The silent pandemic of bacterial antimicrobial resistance is a leading cause of death worldwide, prolonging hospital stays and raising health-care costs. Poor incentives to develop novel pharmacological compounds and the misuse of antibiotics contribute to the bacterial antimicrobial resistance crisis. Therapeutic drug monitoring (TDM) based on blood analysis can help alleviate the emergence of bacterial antimicrobial resistance and effectively decreases the risk of toxic drug concentrations in patients' blood. Antibiotic tissue penetration can vary in patients who are critically or chronically ill and can potentially lead to treatment failure. Antibiotics such as ß-lactams and glycopeptides are detectable in non-invasively collectable biofluids, such as sweat and exhaled breath. The emergence of wearable sensors enables easy access to these non-invasive biofluids, and thus a laboratory-independent analysis of various disease-associated biomarkers and drugs. In this Personal View, we introduce a three-level model for TDM of antibiotics to describe concentrations at the site of infection (SOI) by use of wearable sensors. Our model links blood-based drug measurement with the analysis of drug concentrations in non-invasively collectable biofluids stemming from the SOI to characterise drug concentrations at the SOI. Finally, we outline the necessary clinical and technical steps for the development of wearable sensing platforms for SOI applications.

Reverse Engineering of Digital Measures: Inviting Patients to the Conversation.

Background: Digital measures offer an unparalleled opportunity to create a more holistic picture of how people who are patients behave in their real-world environments, thereby establishing a better connection between patients, caregivers, and the clinical evidence used to drive drug development and disease management. Reaching this vision will require achieving a new level of co-creation between the stakeholders who design, develop, use, and make decisions using evidence from digital measures. Summary: In September 2022, the second in a series of meetings hosted by the Swiss Federal Institute of Technology in Zürich, the Foundation for the National Institutes of Health Biomarkers Consortium, and sponsored by Wellcome Trust, entitled "Reverse Engineering of Digital Measures," was held in Zurich, Switzerland, with a broad range of stakeholders sharing their experience across four case studies to examine how patient centricity is essential in shaping development and validation of digital evidence generation tools. Key Messages: In this paper, we discuss progress and the remaining barriers to widespread use of digital measures for evidence generation in clinical development and care delivery. We also present key discussion points and takeaways in order to continue discourse and provide a basis for dissemination and outreach to the wider community and other stakeholders. The work presented here shows us a blueprint for how and why the patient voice can be thoughtfully integrated into digital measure development and that continued multistakeholder engagement is critical for further progress.

Wearable sweat analysis to determine biological age.

A real-time, noninvasive, and clinically applicable aging test in humans has yet to be established. Herein we propose a sweat- and wearable-based test to determine biological age. This test would empower users to monitor their aging process and take an active role in managing their lifestyle and health.

The dominant logic of Big Tech in healthcare and pharma.

Digital health and digital pharma are considered supportive tools for patients and healthcare providers (HCPs), making the market highly attractive for industry players. Not surprisingly, Tech Giants have started to move into this area. We utilized established management models and publicly available information sources, such as annual company reports, and performed a thorough analysis to uncover the underlying business models of Alphabet, Amazon, Apple, IBM, and Microsoft in order to better understand their intention and course of entering the healthcare and pharma industries. Our results indicate that Big Tech or Tech Giants do address the needs of patients and physicians, while having built clear value propositions, value chains, and revenue models to sustainably revolutionize the healthcare and pharma industries.

Learning how to perform ultrasound-guided interventions with and without augmented reality visualization: a randomized study.

OBJECTIVES: Augmented reality (AR), which entails overlay of in situ images onto the anatomy, may be a promising technique for assisting image-guided interventions. The purpose of this study was to investigate and compare the learning experience and performance of untrained operators in puncture of soft tissue lesions, when using AR ultrasound (AR US) compared with standard US (sUS). METHODS: Forty-four medical students (28 women, 16 men) who had completed a basic US course, but had no experience with AR US, were asked to perform US-guided biopsies with both sUS and AR US, with a randomized selection of the initial modality. The experimental setup aimed to simulate biopsies of superficial soft tissue lesions, such as for example breast masses in clinical practice, by use of a turkey breast containing olives. Time to puncture(s) and success (yes/no) of the biopsies was documented. All participants completed questionnaires about their coordinative skills and their experience during the training. RESULTS: Despite having no experience with the AR technique, time to puncture did not differ significantly between AR US and sUS (median [range]: 17.0 s [6-60] and 14.5 s [5-41], p = 0.16), nor were there any gender-related differences (p = 0.22 and p = 0.50). AR US was considered by 79.5% of the operators to be the more enjoyable means of learning and performing US-guided biopsies. Further, a more favorable learning curve was achieved using AR US. CONCLUSIONS: Students considered AR US to be the preferable and more enjoyable modality for learning how to obtain soft tissue biopsies; however, they did not perform the biopsies faster than when using sUS. KEY POINTS: • Performance of standard and augmented reality US-guided biopsies was comparable • A more favorable learning curve was achieved using augmented reality US. • Augmented reality US was the preferred technique and was considered more enjoyable.

Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial.

Osteoarthritis (OA) is a common, debilitating, chronic disease with no disease-modifying drug approved to date. We discovered LNA043-a derivative of angiopoietin-like 3 (ANGPTL3)-as a potent chondrogenesis inducer using a phenotypic screen with human mesenchymal stem cells. We show that LNA043 promotes chondrogenesis and cartilage matrix synthesis in vitro and regenerates hyaline articular cartilage in preclinical OA and cartilage injury models in vivo. LNA043 exerts at least part of these effects through binding to the fibronectin receptor, integrin α5ß1 on mesenchymal stem cells and chondrocytes. In a first-in-human (phase 1), randomized, double-blinded, placebo-controlled, single ascending dose, single-center trial ( NCT02491281 ; sponsored by Novartis Pharmaceuticals), 28 patients with knee OA were injected intra-articularly with LNA043 or placebo (3:1 ratio) either 2 h, 7 d or 21 d before total knee replacement. LNA043 met its primary safety endpoint and showed short serum pharmacokinetics, cartilage penetration and a lack of immunogenicity (secondary endpoints). Post-hoc transcriptomics profiling of cartilage revealed that a single LNA043 injection reverses the OA transcriptome signature over at least 21 d, inducing the expression of hyaline cartilage matrix components and anabolic signaling pathways, while suppressing mediators of OA progression. LNA043 is a novel disease-modifying OA drug candidate that is currently in a phase 2b trial ( NCT04864392 ) in patients with knee OA.

[Interprofessional Training for Discharge Planning: Effects of Self-Efficacy in Nursing and Medical Students]. / Interprofessionelle Schulung für die Spital-Austrittsplanung: Effekte der Selbstwirksamkeit bei Pflege- und Medizinstudierenden.

Interprofessional Training for Discharge Planning: Effects of Self-Efficacy in Nursing and Medical Students Abstract. Concordant and methodical briefing about a patient's disposition for discharge from hospital within the interprofessional ward round can facilitate a timely discharge. However, interprofessional ward rounds require not only professional skills but also knowledge of interprofessional cooperation between all the occupational groups involved. The question arose whether students of the various professions could learn the necessary competencies during their studies. To this end, a training course on interprofessional discharge planning was developed for nursing and medical students. The training includes four phases consisting of flipped classroom and interprofessional skills training. After each phase, a questionnaire was distributed to assess the self-efficacy of participating nursing and medical students regarding their interprofessional collaboration skills. The results showed that self-efficacy increased steadily with increasing study duration from phase 1 to 4. The study also shows that despite the differences between nursing and medical school curricula, students' self-efficacy regarding interprofessional collaboration skills increased during the IAVI training, which strongly suggests that they benefited from the training.

[Teaching Interprofessional Patient Pathways in Medical Education in Switzerland - A Collaboration of Multiple Players]. / Lehrveranstaltung zu interprofessionellen Versorgungsketten in der Schweiz.

Teaching Interprofessional Patient Pathways in Medical Education in Switzerland - A Collaboration of Multiple Players Abstract. The increase of chronic and complex medical disorders challenges actors in the health care system and affects the entire health care system in Switzerland. Through an interprofessional exchange between medical and health care professionals, the individual needs of patients can be better addressed, which has a positive impact on patients' treatments. To prepare students of the Bachelor of Medicine at ETH Zurich for these challenges, the ETH has designed a specific course together with four educational institutions, which is oriented towards the interprofessional, patient-centred supply chain. The aim of this interprofessional module is, that Bachelor of Medicine students, as well as Pharmacy and Nursing students, acquire knowledge about the other areas of responsibility and competences, and at the same time get to know the interfaces of interprofessional cooperations.

Problem-solving in virtual environment simulations prior to direct instruction for differential diagnosis in medical education: An experimental study.

Background: Despite acquiring vast content knowledge about the functioning of the human body through university teaching, medical students struggle to transfer that knowledge to one of the core disciplinary practices - differential diagnosis. The authors aimed to overcome this problem by implementing computer-based virtual environment simulations in medical education courses. Methods: In an experimental study, the authors compared problem-solving in medical computer-based virtual environment simulations prior to instruction with an instruction-first approach. They compared the effects on isomorphic testing and transfer performance of clinical knowledge and clinical reasoning skills as well as evoked learning mechanisms. The study took place in spring 2021 with undergraduate medical students in the scope of a medical trajectory course. Due to Corona-Virus-19 measures participants completed all study activities remotely from home. Results: The authors did not find any learning activity sequence to be superior to the other. However, when looking at the two learning activities individually, they found that problem-solving in computer-based virtual environment simulations and direct instruction might be equally effective for learning content knowledge. Nevertheless, problem-solving in computer-based virtual environment simulations with formative feedback might be more effective for learning clinical reasoning skills than mere instruction. Conclusions: The findings indicate that problem-solving in computer-based virtual environment simulations might be more effective for learning clinical reasoning skills than mere theoretical instruction. The present study has a high level of ecological validity because it took place in a realistic setting where students had to perform all learning and testing tasks autonomously.

COVID-19 as a chance for hybrid teaching concepts.

COVID-19 has turned the 2020 spring semester upside down. Three days before the start of the block week of the "Teamwork" module, the Federal Office of Public Health (FOPH) announced the ban on live interaction, which made it impossible to conduct five days of practice in the simulation centre of the University Hospital of Zurich. But how can the teaching of all the learning objectives necessary for medical training be guaranteed during an exceptional situation with constantly changing conditions? In the case of the BSc Human Medicine at ETH Zurich (ETHZ), the answer is: Hybrid teaching. The field report "COVID-19 as a chance for hybrid teaching concepts" outlines how ETHZ switched to hybrid teaching within a very short time and how hospital placements were combined with video conferences. The qualitative surveys conducted at the end of the semester and the weekly quantitative surveys of students from March to June indicate the importance of personal exchange despite the ban on contact and that interactivity is possible even without physical proximity. An example from the autumn semester will also be used to show which aspects have proved to be successful and can therefore be retained.

[Bachelor of Human Medicine at the ETH Zurich. A Contribution to the Training of Tomorrow's Physicians]. / Bachelor Humanmedizin an der ETH Zürich.

Bachelor of Human Medicine at the ETH Zurich. A Contribution to the Training of Tomorrow's Physicians Abstract. With ever-changing lifestyles and an increasingly older but also more dynamic society, the maintenance and health as well as the improvement of treatment play a central role. At the same time, developments in bioinformatics, molecular biosciences and imaging techniques are revolutionizing medicine. In order to fully exploit the new possibilities, for example in medical technology or personalised medicine, doctors with a sound knowledge in several disciplines will be needed in the future. In-depth knowledge in the medical, technical and biological sciences will become indispensable. This is where the new Bachelor of Human Medicine at the Swiss Federal Institute of Technology (ETH) Zurich has been in place since autumn 2017, combining medical with technical and scientific aspects of human health. In addition to traditional medical content, it also covers topics from the bioinformatics and medical technology sectors. The continuation of the studies takes place at one of the partner universities in Basel, Lugano or Zurich.