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Teaching medical statistics for students of human medicine should include both theoretical content as well as its implementation in practice using statistical software. The training period with a software may be time-consuming individually, so there is a risk that imparting methodological skills comes up short in such courses. The flipped classroom concept aims at students to familiarize themselves with both the statistical software and the theoretical content in an individual learning phase prior to the course. Then, within an attendance course deepening both aspects under the lecturer’s supervision is possible. Availability of the software as well as a variety of material to prepare the course are essential presumptions for the flipped classroom to be successful. We present the concept and implementation of an online flipped classroom course using the software SAS Studio. Students used their own devices (laptops or tablets) during the self-learning and examination phases, respectively. The pure online implementation in the flipped classroom setting enabled to contribute to an equalisation of the study plan. Moreover, even more students had the opportunity to participate in this practically oriented course in medical statistics. Initial evaluation results demonstrated that the course is well-accepted among students, while the students’ performance level was similar when compared to a non-flipped teaching approach.

Background: Biostatistics is an integral part of the studies of human medicine. Students learn the basics of analyzing and interpreting study results. It is important to demonstrate the subject’s relevance by means of appropriate measures to maximize learning success. We investigated whether an active involvement of students in the process of data collection may improve test performance and motivation among medical students.Methods: We conducted a pilot study comparing active involvement of students (n1=45) in the process of data collection and standard education (n2=26). All students of this pilot study participated in an observational study assessing their preferences regarding sweets or salty munchies, and students of the experimental group subsequently used this data set during the exercises throughout the semester. Primary and secondary endpoints were examination success and motivation respectively. Results: Superiority of the activating teaching method could not be demonstrated (intervention: 109.0 points (SD 8.8), control: 113.8 points (SD 6.5)). The course ratings were superior in the intervention group (median grade 1 vs. median grade 2 in the control group), although this was not a significant improvement (p=0.487). Conclusions: Biostatistics education should incorporate approaches contributing to a better understanding of learning contents. Possible reasons why this pilot study failed to prove superiority of the intervention were a lack of sample size as well as the good grades in the control group. The presented teaching concept has to be evaluated by means of a larger sample enabling more valid conclusions. Furthermore, the considered research question in the experimental group may be changed to a more relevant one for medical practice.

An increasing number of studies are being performed in educational research to evaluate new teaching methods and approaches. These studies could be performed more efficiently and deliver more convincing results if they more strictly applied and complied with recognized standards of scientific studies. Such an approach could substantially increase the quality in particular of prospective, two-arm (intervention) studies that aim to compare two different teaching methods. A key standard in such studies is randomization, which can minimize systematic bias in study findings; such bias may result if the two study arms are not structurally equivalent. If possible, educational research studies should also achieve this standard, although this is not yet generally the case. Some difficulties and concerns exist, particularly regarding organizational and methodological aspects. An important point to consider in educational research studies is that usually individuals cannot be randomized, because of the teaching situation, and instead whole groups have to be randomized (so-called “cluster randomization”). Compared with studies with individual randomization, studies with cluster randomization normally require (significantly) larger sample sizes and more complex methods for calculating sample size. Furthermore, cluster-randomized studies require more complex methods for statistical analysis. The consequence of the above is that a competent expert with respective special knowledge needs to be involved in all phases of cluster-randomized studies.Studies to evaluate new teaching methods need to make greater use of randomization in order to achieve scientifically convincing results. Therefore, in this article we describe the general principles of cluster randomization and how to implement these principles, and we also outline practical aspects of using cluster randomization in prospective, two-arm comparative educational research studies.

Alveolar echinococcosis (AE) is the most Iethal human helminthic infection. The malignancy-like disease is rare, but morbidity and treatment costs are high. Objective of the study was to identify factors at baseline and during specific AE therapy influencing the long-term outcome of the disease.All patients with AE seen at the specialized treatment unit in Ulm between January 1992 and December 2011 were included in the analysis.The data of 312 patients were analyzed; 108 were diagnosed before 2000 (series A), 204 since 2000 (series B); 290 received specific AE treatment. Patients of series B were more often symptom-free at diagnosis (44.1% vs. 21.3%), had lower disease stages (50.0% vs. 34.2%) and more complete resections (57.7% vs. 20.0%), but higher rates of side effects and drug toxicity (54.1% vs. 40.8%). In series B, more patients remained relapse- or progression-free after 5 years (90.5% vs. 82.8%); after 10 years, the ratio of relapses converged (70.3% vs. 66.9%, p=0.0507). Relapses or progression occurred more often after incomplete surgery or long treatment pauses. The 5-year and 10-year survival rates were 96.9% and 90.6%, respectively, and 17% of the patients were cured.We observed a shift towards early diagnosis, earlier initiation of specific therapy and more complete resections after 2000. Although diagnosis and treatment of AE pose a challenge, with an individual interdisciplinary management 88.8% of the patients have a favorable outcome.

The COVID-19 course and immunity differ in children and adults. We analyzed immune response dynamics in 28 families up to 12 months after mild or asymptomatic infection. Unlike adults, the initial response is plasmablast-driven in children. Four months after infection, children show an enhanced specific antibody response and lower but detectable spike 1 protein (S1)-specific B and T cell responses than their parents. While specific antibodies decline, neutralizing antibody activity and breadth increase in both groups. The frequencies of S1-specific B and T cell responses remain stable. However, in children, one year after infection, an increase in the S1-specific IgA class switch and the expression of CD27 on S1-specific B cells and T cell maturation are observed. These results, together with the enhanced neutralizing potential and breadth of the specific antibodies, suggest a progressive maturation of the S1-specific immune response. Hence, the immune response in children persists over 12 months but dynamically changes in quality, with progressive neutralizing, breadth, and memory maturation. This implies a benefit for booster vaccination in children to consolidate memory formation.

[english] During every summer term at Ulm University the obligatory course of biometry (Q1) is taught in a PC pool using the statistical software SAS Analyst. Short examinations are performed at each of the 6 course dates summing the results over the term. This examination principle has proved to be worthwhile, because a continuous learning of the students during the whole term can be achieved by this.Some problems have to be resolved before realization. Among others, the time problem within the exercise has to be solved, as well as the formal criteria which have to be met. In addition, more time will be needed for the correction, because all students get individual data for the exams and so a standardisation is not possible.To solve these problems we have implemented the following points into our examination tool:The new system has been developed with different software-tools, whereas the main aspects have been realized by the statistical software SAS as well as MS Office programmes MS Excel and MS Access.[german] Im Fach Medizinische Biometrie/Querschnittsfach Q1 an der Universität Ulm wird jeweils in jedem Sommersemester das Pflichtseminar in einem PC Pool anhand der Statistiksoftware SAS-Analyst gelehrt. Dieser Kurs soll semesterbegleitend an jedem der sechs Termine anhand von Kurztests abgeprüft werden. Diese Prüfungsform hat sich bewährt, da so eine kontinuierliche Mitarbeit der Studierenden über das gesamte Semester erreicht wird. Die Umsetzung dieser Vorgehensweise birgt allerdings einige Probleme: Unter anderem muss das Zeitproblem in der Übung gelöst sowie die Prüfungssituation formal eingehalten werden. Außerdem ergibt sich so ein Mehraufwand für die Korrektur, da jeder Studierende einen eigenen individuellen Datensatz bei der Prüfung bekommt und so keine Standardisierung bei manueller Korrektur auf Papierbasis möglich ist.Um diesen Problemen zu begegnen, haben wir in dem vorzustellenden Prüfungstool folgende Punkte umgesetzt:Das vorgesehene System ist mit mehreren Software-Tools entwickelt worden, wobei die wesentlichen Aspekte in der Statistiksoftware SAS sowie MS-Office-Programmen – MS-Excel und MS-Access – realisiert wurden.

Teaching practical skills is of particular interest in the study of human medicine. With regard to medical statistics this means the use of statistical software, which may be effectively taught by a flipped classroom approach. As a pilot study, we designed and implemented an elective course on medical statistics that focused on hands-on data analysis in SAS Studio. Students independently prepared for class using materials such as pretaped asynchronous lectures, and worked on exercises during synchronous class sessions. On course evaluations completed by n 15 students out of 26, students rated their satisfaction with the course a mean of 1.3 (SD 0.6) on a scale where 1 best and 6 worst. Twelve (80%) indicated that they processed all materials provided, and 11 students (73%) rated the frequency of direct contact with the instructor as sufficient. Nearly all (14 out of 15) viewed the course as an adequate substitute for a full face-to-face course. Our results suggest that the proposed course design is well-accepted. The flipped classroom format offers high flexibility and can be implemented easily online. Our pilot data are encouraging regarding the aim of designing a prospective follow-up study which compares the flipped classroom approach to a teaching format based on attendance.

In medical research missing values often arise in the course of a data analysis. This fact constitutes a problem for different reasons, so e.g. standard methods for analyzing data lead to biased estimates and a loss of statistical power due to missing values, since those methods require complete data sets and therefore omit incomplete cases for the analyses. Furthermore missing values imply a certain loss of information for what reason the validity of results of a study with missing values has to be rated less than in a case where all data had been available. For years there are methods for replacement of missing values (Rubin, Schafer) to tackle these problems and solve them in parts. Hence in this article we want to present the existing software to handle and replace missing values on the one hand and give an outline about the available options to get information on the other hand. The methodological aspects of the replacement strategies are delineated just briefly in this article.

Human alveolar echinococcosis is a rare disease that can be caused by the parasite Echinococcus multilocularis (1,2). The pathogen E. multilocularis and human cases of the disease are predominantly distributed [...]

Background: Neuropathologic studies of brains from autopsy series show tau inclusions (pretangles, neuropils threads, neurofibrillary tangles) are detectable more than a decade before amyloid-β (Aβ) deposition in Alzheimer's disease (AD) and develop in a characteristic manner that forms the basis for AD staging. An alternative position views pathological tau without Aβ deposition as a 'primary age-related tauopathy' (PART) rather than prodromal AD. Recently, an early focus of tau inclusions in the Ammon's horn second sector (CA2) with relative sparing of CA1 that occurs before tau inclusions develop in the entorhinal cortex (EC) was proposed as an additional feature of PART. Objective: To test the 'definite PART' hypothesis. Methods: We used AT8-immunohistochemistry in 100μm sections to examine the EC, transentorhinal cortex (TRE), and Ammon's horn in 325 brains with tau inclusions lacking Aβ deposits (average age at death 66.7 years for females, 66.4 years for males). Results: 100% of cases displayed tau inclusions in the TRE. In 89% of cases, the CA1 tau rating was greater than or equal to that in CA2. In 25%, CA2 was devoid of tau inclusions. Only 4% displayed a higher tau score in CA2 than in the TRE, EC, and CA1. The perforant path also displayed early tau changes. APOE genotyping was available for 199/325 individuals. Of these, 44% had an ɛ4 allele that placed them at greater risk for developing later NFT stages and, therefore, clinical AD. Conclusions: Our new findings call into question the PART hypothesis and are consistent with the idea that our cases represent prodromal AD. [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) causes severe birth defects and can be transmitted via sexual intercourse. Semen from ZIKV-infected individuals contains high viral loads and may therefore serve as an important vector for virus transmission. Here we analyze the effect of semen on ZIKV infection of cells and tissues derived from the anogenital region. ZIKV replicates in all analyzed cell lines, primary cells, and endometrial or vaginal tissues. However, in the presence of semen, infection by ZIKV and other flaviviruses is potently inhibited. We show that semen prevents ZIKV attachment to target cells, and that an extracellular vesicle preparation from semen is responsible for this anti-ZIKV activity. Our findings suggest that ZIKV transmission is limited by semen. As such, semen appears to serve as a protector against sexual ZIKV transmission, despite the availability of highly susceptible cells in the anogenital tract and high viral loads in this bodily fluid.

While most German anatomy institutes provide only limited information about body donors and their lives, students have expressed a desire to learn more about these individuals, especially about their motivations to donate their bodies for the sake of medical education. In order to gratify this wish, as well as to further humanize body donors, an educational film was compiled, and a study designed to capture the film's effects on medical students. This is the first study using standardized, validated psychological tools to evaluate the impact of an educational film about body donors on students' empathy and psychological stress levels. The study followed a longitudinal, controlled, and cluster randomized design, including 77 (48 females/29 males) participants who watched the video either before, midway, or after the dissection course. Questionnaires were completed at four points in time applying the Jefferson Scale for Empathy (JSPE-S) and the Interpersonal Reactivity Index (IRI) to measure empathy. Psychological stress levels were recorded by the Brief Symptom Inventory (BSI). Overall, students recommended the film to be shown to all students (median 6.0; maximum on the six-point Likert scale). Viewing the film revealed no significant changes between study groups or over time in JSPE-S sum scores. All groups demonstrated a significant reduction of BSI values before the dissection course actually started and increased values during the course, but both developments appeared not to be associated with the intervention. Overall, the educational film did not correlate with any negative effects on students' empathy and psychological stress levels, and it was strongly approved of by students, as it provided more humanizing personal information about body donors without violating their anonymity.

BACKGROUND. Results of many randomized trials on COVID-19 convalescent plasma (CCP) have been reported, but information on long-term outcome after CCP treatment is limited. The objectives of this extended observation of the randomized CAPSID trial are to assess long-term outcome and disease burden in patients initially treated with or without CCP. METHODS. Of 105 randomized patients, 50 participated in the extended observation. Quality of life (QoL) was assessed by questionnaires and a structured interview. CCP donors (n = 113) with asymptomatic to moderate COVID-19 were included as a reference group. RESULTS. The median follow-up of patients was 396 days, and the estimated 1-year survival was 78.7% in the CCP group and 60.2% in the control (P = 0.08). The subgroup treated with a higher cumulative amount of neutralizing antibodies showed a better 1-year survival compared with the control group (91.5% versus 60.2%, P = 0.01). Medical events and QoL assessments showed a consistent trend for better results in the CCP group without reaching statistical significance. There was no difference in the increase in neutralizing antibodies after vaccination between the CCP and control groups. CONCLUSION. The trial demonstrated a trend toward better outcome in the CCP group without reaching statistical significance. A predefined subgroup analysis showed a significantly better outcome (long-term survival, time to discharge from ICU, and time to hospital discharge) among those who received a higher amount of neutralizing antibodies compared with the control group. A substantial long-term disease burden remains after severe COVID-19. TRIAL REGISTRATION. EudraCT 2020-001310-38 and ClinicalTrials.gov NCT04433910. FUNDING. Bundesministerium fur Gesundheit (German Federal Ministry of Health)., Introduction The use of COVID-19 convalescent plasma (CCP) from patients recovered from a SARS-CoV-2 infection was evaluated in many randomized trials during the pandemic (1-21). The trials were heterogeneous in [...]

Background and purpose: The predictive value of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) for apheresis outcome in steroid‐refractory multiple sclerosis (MS) relapse has not yet been evaluated. Methods: We used pre‐ and postapheresis serum samples from 38 participants of the IAPEMS trial (clinicaltrials.gov: NCT02671682), which investigated the use of immunoadsorption versus plasma exchange for the treatment of steroid‐refractory MS attacks. Response to apheresis was classified based on improvement on (i) the Expanded Disability Status Scale (EDSS), (ii) the affected functional system scores (FSS) of the EDSS, or (iii) the visual acuity for patients with optic neuritis, 4 weeks postapheresis. sNFL and sGFAP were measured by single molecule arrays. Results: Preprocedural sGFAP levels could discriminate between responders and nonresponders, determined by FSS improvement (p = 0.017). In multivariate logistic regression analysis, younger age (odds ratio [OR] = 0.781, 95% confidence interval [CI] = 0.635–0.962, p = 0.020) and lower sGFAP levels (OR = 0.948, 95% CI = 0.903–0.995, p = 0.031) could predict response to apheresis in the overall cohort. We could observe a trend towards a favourable apheresis outcome with higher sNfL levels (OR = 1.413, 95% CI = 0.965–2.069, p = 0.076). Analysis of the sNfL‐to‐sGFAP ratio showed an OR of 1.924 (95% CI = 1.073–3.451, p = 0.028) for predicting apheresis response. The ratio showed a better predictive value than the individual parameters. Neither biomarker was affected by the number of steroid cycles preapheresis. Conclusions: Lower sGFAP levels, a higher sNfL‐to‐sGFAP ratio, and younger age are associated with a favourable apheresis outcome. [ABSTRACT FROM AUTHOR]