Virtual reality as a teaching method for resuscitation training in undergraduate first year medical students: a randomized controlled trial.

BACKGROUND: Virtual reality is an innovative technology for medical education associated with high empirical realism. Therefore, this study compares a conventional cardiopulmonary resuscitation (CPR) training with a Virtual Reality (VR) training aiming to demonstrate: (a) non-inferiority of the VR intervention in respect of no flow time and (b) superiority in respect of subjective learning gain. METHODS: In this controlled randomized study first year, undergraduate students were allocated in the intervention group and the control group. Fifty-six participants were randomized to the intervention group and 104 participants to the control group. The intervention group received an individual 35-min VR Basic Life Support (BLS) course and a basic skill training. The control group took part in a "classic" BLS-course with a seminar and a basic skill training. The groups were compared in respect of no flow time in a final 3-min BLS examination (primary outcome) and their learning gain (secondary outcome) assessed with a comparative self-assessment (CSA) using a questionnaire at the beginning and the end of the course. Data analysis was performed with a general linear fixed effects model. RESULTS: The no flow time was significantly shorter in the control group (Mean values: control group 82 s vs. intervention group 93 s; p = 0.000). In the CSA participants of the intervention group had a higher learning gain in 6 out of 11 items of the questionnaire (p < 0.05). CONCLUSION: A "classic" BLS-course with a seminar and training seems superior to VR in teaching technical skills. However, overall learning gain was higher with VR. Future BLS course-formats should consider the integration of VR technique into the classic CPR training or vice versa, to use the advantage of both teaching techniques.

Implementation of Basic Life Support training in schools: a randomised controlled trial evaluating self-regulated learning as alternative training concept.

BACKGROUND: The Kids save lives statement recommends annual Basic Life Support (BLS) training for school children but the implementation is challenging. Trainings should be easy to realise and every BLS training should be as effective as possible to prepare learners for lifesaving actions. Preparedness implies skills and positive beliefs in the own capability (high self-efficacy). METHODS: This randomized controlled cluster study investigates, if self-regulated learning promotes self-efficacy and long-term retention of practical BLS skills. Students in the age of 12 years participated in a practical training in BLS and a scenario testing of skills. In the control group the practical training was instructor-led. In the intervention group the students self-regulated their learning processes and feedback was provided by the peer-group. The primary outcome self-efficacy for helping in cardiac arrest after the training and 9 months later was analysed using a multilevel mixed model. Means and pass-rates for BLS skills were secondary outcomes. RESULTS: Contrary to the assumptions, this study could not measure a higher self-efficacy for helping in cardiac arrest of the students participating in the intervention (n = 307 students) compared to the control group (n = 293 students) after training and at the follow-up (mean difference: 0.11 points, 95% CI: - 0.26 to 0.04, P = 0.135). The odds to pass all items of the BLS exam was not significantly different between the groups (OR 1.11, 95% CI: 0.81 to 1.52, p = 0.533). Self-regulated learning was associated with a higher performance of male students in the BLS exam (mean score: 7.35) compared to females of the intervention (female: 7.05) and compared to males of the control (7.06). CONCLUSION: This study could not resolve the question, if self-regulated learning in peer-groups improves self-efficacy for helping in cardiac arrest. Self-regulated learning is an effective alternative to instructor-led training in BLS skills training and may be feasible to realise for lay-persons. For male students self-regulated learning seems to be beneficial to support long-term retention of skills. TRIAL REGISTRATION: ISRCTN17334920, retrospectively registered 07.03.2019.

Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme.

A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognosis. Therefore, a comprehensive expression analysis of S1P receptors (S1P1-S1P5) and S1P metabolizing enzymes in human GBM (n = 117) compared to healthy brain (n = 10) was performed to evaluate their role for patient´s survival. Furthermore, influence of S1P receptor inhibition on proliferation and migration were studied in LN18 GBM cells. Compared to control brain, mRNA levels of S1P1, S1P2, S1P3 and S1P generating sphingosine kinase-1 were elevated in GBM. Kaplan-Meier analyses demonstrated an association between S1P1 and S1P2 with patient´s survival times. In vitro, an inhibitory effect of the SphK inhibitor SKI-II on viability of LN18 cells was shown. S1P itself had no effect on viability but stimulated LN18 migration which was blocked by inhibition of S1P1 and S1P2. The participation of S1P1 and S1P2 in LN18 migration was further supported by siRNA-mediated silencing of these receptors. Immunoblots and inhibition experiments suggest an involvement of the PI3-kinase/AKT1 pathway in the chemotactic effect of S1P in LN18 cells.In summary, our data argue for a role of S1P signaling in proliferation and migration of GBM cells. Individual components of the S1P pathway represent prognostic factors for patients with GBM. Perspectively, a selective modulation of S1P receptor subtypes could represent a therapeutic approach for GBM patients and requires further evaluation.

A workflow-driven approach to integrate generic software modules in a Trusted Third Party.

BACKGROUND: Cohort studies and registries rely on massive amounts of personal medical data. Therefore, data protection and information security as well as ethical aspects gain in importance and need to be considered as early as possible during the establishment of a study. Resulting legal and ethical obligations require a precise implementation of appropriate technical and organisational measures for a Trusted Third Party. METHODS: This paper defines and organises a consistent workflow-management to realize a Trusted Third Party. In particular, it focusses the technical implementation of a Trusted Third Party Dispatcher to provide basic functionalities (including identity management, pseudonym administration and informed consent management) and measures required to meet study specific conditions of cohort studies and registries. Thereby several independent open source software modules developed and provided by the MOSAIC project are used. This technical concept offers the necessary flexibility and extensibility to address legal and ethical requirements of individual scenarios. RESULTS: The developed concept for a Trusted Third Party Dispatcher allows mapping single process steps as well as individual requirements and characteristics of particular studies to workflows, which in turn can be combined to model complex Trusted Third Party processes. The uniformity of this approach permits unrestricted re-combination of the available functionalities (depending on the applied software modules) for various research projects. CONCLUSION: The proposed approach for the technical implementation of an independent Trusted Third Party reduces the effort for scenario specific implementations as well as for maintenance. The applicability and the efficacy of the concept for a workflow-driven Trusted Third Party could be confirmed during the establishment of several nationwide studies (e.g. German Centre for Cardiovascular Research and the National Cohort).

Pim1 kinase is upregulated in glioblastoma multiforme and mediates tumor cell survival.

BACKGROUND: The current therapy for glioblastoma multiforme (GBM), the most aggressive and common primary brain tumor of adults, involves surgery and a combined radiochemotherapy that controls tumor progression only for a limited time window. Therefore, the identification of new molecular targets is highly necessary. Inhibition of kinases has become a standard of clinical oncology, and thus the oncogenic kinase Pim1 might represent a promising target for improvement of GBM therapy. METHODS: Expression of Pim1 and associated signaling molecules was analyzed in human GBM samples, and the potential role of this kinase in patients' prognosis was evaluated. Furthermore, we analyzed the in vivo role of Pim1 in GBM cell growth in an orthotopic mouse model and examined the consequences of Pim1 inhibition in vitro to clarify underlying pathways. RESULTS: In comparison with normal brain, a strong upregulation of Pim1 was demonstrated in human GBM samples. Notably, patients with short overall survival showed a significantly higher Pim1 expression compared with GBM patients who lived longer than the median. In vitro experiments with GBM cells and analysis of patients' GBM samples suggest that Pim1 regulation is dependent on epidermal growth factor receptor. Furthermore, inhibition of Pim1 resulted in reduced cell viability accompanied by decreased cell numbers and increased apoptotic cells, as seen by elevated subG1 cell contents and caspase-3 and -9 activation, as well as modulation of several cell cycle or apoptosis regulatory proteins. CONCLUSIONS: Altogether, Pim1 could be a novel therapeutic target, which should be further analyzed to improve the outcome of patients with aggressive GBM.

Cohort profile: Greifswald approach to individualized medicine (GANI_MED).

BACKGROUND: Individualized Medicine aims at providing optimal treatment for an individual patient at a given time based on his specific genetic and molecular characteristics. This requires excellent clinical stratification of patients as well as the availability of genomic data and biomarkers as prerequisites for the development of novel diagnostic tools and therapeutic strategies. The University Medicine Greifswald, Germany, has launched the "Greifswald Approach to Individualized Medicine" (GANI_MED) project to address major challenges of Individualized Medicine. Herein, we describe the implementation of the scientific and clinical infrastructure that allows future translation of findings relevant to Individualized Medicine into clinical practice. METHODS/DESIGN: Clinical patient cohorts (N > 5,000) with an emphasis on metabolic and cardiovascular diseases are being established following a standardized protocol for the assessment of medical history, laboratory biomarkers, and the collection of various biosamples for bio-banking purposes. A multi-omics based biomarker assessment including genome-wide genotyping, transcriptome, metabolome, and proteome analyses complements the multi-level approach of GANI_MED. Comparisons with the general background population as characterized by our Study of Health in Pomerania (SHIP) are performed. A central data management structure has been implemented to capture and integrate all relevant clinical data for research purposes. Ethical research projects on informed consent procedures, reporting of incidental findings, and economic evaluations were launched in parallel.

Efficient data management in a large-scale epidemiology research project.

This article describes the concept of a "Central Data Management" (CDM) and its implementation within the large-scale population-based medical research project "Personalized Medicine". The CDM can be summarized as a conjunction of data capturing, data integration, data storage, data refinement, and data transfer. A wide spectrum of reliable "Extract Transform Load" (ETL) software for automatic integration of data as well as "electronic Case Report Forms" (eCRFs) was developed, in order to integrate decentralized and heterogeneously captured data. Due to the high sensitivity of the captured data, high system resource availability, data privacy, data security and quality assurance are of utmost importance. A complex data model was developed and implemented using an Oracle database in high availability cluster mode in order to integrate different types of participant-related data. Intelligent data capturing and storage mechanisms are improving the quality of data. Data privacy is ensured by a multi-layered role/right system for access control and de-identification of identifying data. A well defined backup process prevents data loss. Over the period of one and a half year, the CDM has captured a wide variety of data in the magnitude of approximately 5terabytes without experiencing any critical incidents of system breakdown or loss of data. The aim of this article is to demonstrate one possible way of establishing a Central Data Management in large-scale medical and epidemiological studies.

Methods and implementation of a central biosample and data management in a three-centre clinical study.

In our report we describe concept, strategies and implementation of a central biosample and data management (CSDM) system in the three-centre clinical study of the Transregional Collaborative Research Centre "Inflammatory Cardiomyopathy - Molecular Pathogenesis and Therapy" SFB/TR 19, Germany. Following the requirements of high system resource availability, data security, privacy protection and quality assurance, a web-based CSDM was developed based on Java 2 Enterprise Edition using an Oracle database. An efficient and reliable sample documentation system using bar code labelling, a partitioning storage algorithm and an online documentation software was implemented. An online electronic case report form is used to acquire patient-related data. Strict rules for access to the online applications and secure connections are used to account for privacy protection and data security. Challenges for the implementation of the CSDM resided at project, technical and organisational level as well as at staff level.