The present study presents a process evaluation of a performance psychology intervention for transitioning elite and elite musicians. The goal of the intervention was to provide participants with an amalgamation of evidence-informed principles, aimed to improve their quality of practice and performance preparation. The intervention consisted of an educational session followed by four workshops. In total, eight transitioning elite and seven elite musicians participated. Process measures included quantitative and qualitative workshop evaluations, monitoring logs, and semi-structured interviews. Overall, the intervention was evaluated positively by the participants. However, differences were present between the groups, with the elite musicians typically evaluating the intervention more favorably compared to the transitioning elites. Specific positive outcomes included an increased awareness and re-examining of current practice strategies, more structured and goal-directed practice, increased practice efficiency and focus, a more proactive approach to performances, and increased attention for the physical aspects of playing. Moreover, a number of contextual considerations and implementation challenges became evident. Important implications for performance psychology interventions and practitioners in music are discussed. It is increasingly recognized that performance psychology can provide an important added value for classical musicians’ development and performance . This isHowever, it has been argued that psychological interventions overly focus on decreasing performance anxiety and addressing its symptoms – which might not always be realistic nor desirable. As such, these interventions often fail to address how optimal focus of attention, functioning, and performance under pressure might be facilitated . FurtherA limited number of studies have looked at how psychological interventions can improve musicians’ practice activities. For example, As performance psychology in music is growing, several avenues for further research become visible. First, most interventions have been set up as straightforward pre- and post-test evaluations; with e.g.,  or withoSecond, existing performance psychology interventions have primarily focused on music students, with limited attention for musicians situated in other career phases  included fellows of the academy of a world-renowned international orchestra , with a mean age of 23.8 (SD = 1.4) and an average of 18.1 years of experience as a musicians (SD = 2.0). This academy allowed the musicians to work embedded within the orchestra, among other learning opportunities, for the duration of 1 year; with the specific aim to prepare them for the transition into the professional field. During this year, the transitioning elite musicians also engage in a mentorship program with established orchestra members. Instruments played by the transitioning elites included violin (n = 3), cello, viola, clarinet, bass, and harp . Elite musicians (n = 7) included members of one accomplished professional international orchestra . They had a mean age of 44.3 (SD = 13.7), with 35.4 years of experience (SD = 11.3). Instruments played by the elites included violin (n = 2), cello (n = 2), viola, clarinet, and bass . All participants had previously obtained bachelor’s or master’s degrees in music education.Participants in the present study included both transitioning elite and elite musicians. Transitioning elite musicians  it was not possible to organize weekly monitoring sessions with all participants. In these cases, participants were provided the opportunity to deliver any questions or remarks via mail. In total, 66 sessions were organized with the 8 transitioning elite musicians and 46 sessions with the 7 elite musicians. The end of the monitoring sessions was anchored by performance moments. For the transitioning elite group, this performance moment entailed a mock audition organized by the academy. For the elite group, the end of the intervention was marked by the final week of performances during the orchestra season.After the end of the intervention, all participants were invited for a concluding interview. These interviews were scheduled in a quiet place of the participants’ choice and led by the first author, who has extensive experience in qualitative research. Due to practical limitations, two interviews  were done through Skype. Prior to the interviews, participants were also asked to complete the general intervention evaluation. At the conclusion of the interview, participants were thanked for their participation and asked how they would like to be informed about the further results of the project.1.Quantitative preliminary workshop evaluations were gathered with all participants, roughly one week after each workshop. These evaluations always included statements related to the usefulness of the workshop as a whole, each of the principles included in the workshop, the practical exercises, and the factsheets. Answers were rated on a 5-point Likert scale, ranging from 1  to 5 .2.general intervention evaluation was included at the end of the intervention. This evaluation included both general questions related to the whole intervention, as well as specific questions for each workshop component included in the intervention , participants were presented two open-ended questions; “Where there specific things you liked during this workshop?” and “How might we improve this workshop in the future?”2.Monitoring logs were kept by research assistants during all the monitoring sessions. These monitoring logs provided an indication of how frequently participants engaged with the different principles, their experiences and perceived challenges working with the principles, and descriptions of the individualized follow-up.3.semi-structured interviews were conducted with all participants following conclusion of the intervention. An interview guide was developed to give direction to the interviews. This interview guide included four parts; first participants were asked about their general experiences during the intervention . Second, participants were asked specifically about their experiences with each of the intervention principles . Third, participants were asked about some of the experienced challenges during the intervention . Finally, participants were asked about potential areas of improvement for the intervention .Individual t-tests. Additionally, independent sample t-tests were also used to assess differences between the TE and E group for the frequency of use and perceived value of the different workshop components.An exploratory quantitative approach was adopted in the present study to find out if the two expertise groups evaluated the intervention differently. Descriptive statistics were first calculated for all quantitative variables. Between group differences for the general intervention evaluation were assessed using independent sample The qualitative data was analyzed using inductive thematic analysis. This approach was chosen as it is an accessible method to discern, analyze, and report meaning patterns, whilst maintaining theoretical and analytical flexibility . The anaIn line with our explanatory mixed methods research design cf. , quantitM = 4.57, SD = 0.53) compared to the TE group ; t(13) = 4.40, p = 0.001, d = 2.26. Further independent sample t-tests also revealed significantly higher evaluation scores for the E group compared to the TE group for value of the workshops, t(13) = 3.53, p = 0.004, d = 1.82; whether they learned a lot, t(13) = 4.82, p < 0.001, d = 2.49; and value of the monitoring sessions, t(9.80) = 3.22, p = 0.009, d = 1.57.As indicated in the methods section, quantitative results were collected during preliminary workshop evaluations as well as the general intervention evaluation. However, due to space limitations, we only present results from the general intervention evaluation, especially as preliminary evaluations were consistent with the final evaluations. Evaluations of the intervention overall are summarized in t-tests found no significant differences in the frequency of use between the TE and the E groups (ps > 0.05). Although a substantial difference was found for the frequency of use of time management in the TE group  compared to the E group , this difference failed to reach significance; t(13) = −1.80, p = 0.096, d = 0.93. Similarly, a substantial difference was present in the use of scenario planning in the TE group  compared to the E group , which nevertheless failed to reach significance; t(13) = 1.99, p = 0.068, d = 1.04. Despite demonstrating only trends toward significance, both effect sizes did exceed the convention for a large effect (d = 0.80). The ratings for Perceived value of the workshop components ranged between 3.50 and 4.50 for the TE group; and 3.00 and 4.57 for the E group. A large significant difference was present in the perceived value of scenario planning between the TE group  and the E group ; t(13) = 3.55, p = 0.004, d = 1.84. No additional significant differences were found for the perceived value of the different components between the TE and the E groups (ps > 0.05).Evaluations of the different workshop components in relation to frequency of use and perceived value are summarized in intervention outcomes, (b) positive intervention mechanisms, and (c) implementation challenges and improvements. These findings are summarized in I,” “M,” or “P”; indicating that they were derived from the interviews, monitoring logs, or preliminary qualitative evaluations respectively.The qualitative data indicated that participants evaluated the intervention as generally positive. In line with the quantitative findings, E musicians seemed to appraise the intervention somewhat more favorable compared to the TE group. Furthermore, participants also clearly differed in the way they adopted and evaluated the different sub-components of the intervention. This finding was consistent with the goal of the intervention, which was to present the participants with an amalgamation of principles they could selectively use based on their personal preferences. More detailed thematic analysis of the data resulted in three overarching themes: (a) Re-examine practice habits, as highlighted by one E musician: “Yes, [the intervention] brought me a lot. It really inspired me to look differently at the whole aspect of studying and playing music” (E2-I). For several participants this re-examination helped to refresh some old or vague practice methods and make them more concrete: “I think a lot of those things weren’t necessarily new, but it was more like refreshing old methods and start thinking about those again. You’re going to do things again, because you haven’t done them in a long time.” (E6-I); “There were some things that I knew unconsciously, but of which I had never thought about very consciously. So, it was good to refresh that again and to think about what works for me” (TE7-I). In addition, some E musicians stated that re-examining their habits reinvigorated their motivation to practice as well: “It is really motivating because it gives you to feeling that you can still progress.” (E2-I); or “Normally, you get stuck into a pattern. Sometimes it is difficult to motivate yourself and you just have those bad days. So that way I also enjoyed working on it in a fresh way” (E6-I).In total, six sub-themes were identified indicating the perceived positive outcomes gained from the intervention. The first broad theme was that it led participants to Increased awareness, as illustrated by one musician: “Increased awareness, in general, I think was the most beneficial aspect of the intervention” (TE2-I). Among other things, participants stated that during the intervention they gained awareness of the types of goals they were setting in their practice: “It made me more, how to say, more aware. Aware of what goals I set myself, whether they are realistic and if maybe they put too much pressure on myself, or not enough” (TE4-I); “I’m more aware of how I’m practicing, what I’m doing and what I’m doing wrong. What are my goals? Because thanks to that I started to be aware of what I wanted to do more and more” (E6-I). As evidenced by this last quote, participants also became more aware of what they were doing and focusing on during practice. For example, some participants became more aware of the focus they were adopting during practice: “I was more aware when I was practicing internally [focussed]” (TE6-M). Finally, some participants also became more aware of when they were practicing inefficiently or unfocused: “It helped to notice thoughtlessness and automaticity” (TE1-M).Related to re-examining practice habits, a second theme reflected an Structured and goal-directed in their practice. For example, several participants argued that they became much more structured in planning their practice material and organizing their practice time: “I just try to be very conscious about what comes next, not only those concerts in the next few weeks, but also to look further … I don’t know if I would have started this early before this intervention.” (E6-I). In addition to structuring their practice, some musicians also became more deliberate and goal-directed in their day-to-day practice activities. Participants argued that using specific practice goals, particularly helped to them in managing the different pieces they have to learn simultaneously: “It [the intervention] really helped to focus on smaller goals that make you study. It makes it more manageable.” (TE1-M); orAs a third theme, participants argued that they became more I)The goal-setting, for example, for me was really helpful for my organization. Because I have a lot of work and a lot of pieces to play. And if I know I have only about two or three hours before I have my next rehearsals. Sometimes that’s overwhelming and it puts a lot of pressure on me. And if you [plan] it before, it is really helping to structure it all and of course after you made a plan you normally feel less stressed. (TE4-I).Finally, some participants also argued that reflection on their goals helped to inform future practice goals and activities: “I record much more of myself and I can reflect much more on what I have actually done. This also helps to set new goals. Thanks to this intervention, I really learned to do that” . More specifically, for most participants the intervention helped in maintaining an optimal focus during practice. This was, for example, referenced in relation to the deliberate practice strategies: “I particularly found that the structured practice, dividing the practice time into shorter, more manageable blocks, was very effective. Also planning exactly what I wanted to work on helped me to focus on what I needed to do most.” (E4-I); “I used the [structured practice] when I was tired and it worked quite well, because it contains very short practice blocks in which I could focus clearly.” (TE1-I). Furthermore, some participants also stated that the use of imagery improved focus: “For me [imagery] especially helped for my concentration. To make your body gets quiet, but your brain still can work how it wants to. It really helped me to focus.” (TE4-I). Finally, the use of external focus of attention was also referenced as a method to practice and play more effectively:A fourth perceived benefit of the intervention related to I)I think external focus is very important. I noticed while teaching and also while practicing myself, as soon as I think of something as an image or a long line, then it is so often that technical things solve themselves. This remains some kind of miracle for me. If you’re zooming in on the technical parts it won’t succeed, but when you think of it as a landscape it works out. Your body knows what to do and you just block it with thinking of technical elements. ;In combination with imagery or planned disruptions, I thought about the scenarios and actively searched for solutions. I then tried out how it would feel [to experience] those what-if scenarios. It helped me to feel the stress and feel that I can play under these circumstances. (TE8-I)I used [imagery] a lot and certainly toward the audition, which also has to do with training under pressure and the what-if scenarios. Doing it every day a few times to prepare for everything. That helped for sure, because when I had my audition, I had already walked into the building a hundred times and all sorts of things went wrong. So that was really nice for practicing. (TE1-M); “It helped to hide my nerves more. I felt more relaxed and my thoughts weren’t about internal focus anymore.” (TE4-M).In addition to feeling prepared, several participants also stated that the strategies helped them to be less stressed for performances and allowed them to adopt a more desirable  focus of attention: “I’m calmer in my head and can focus more on the interpretation of the music instead of difficult notes for example.” ; “I had some pain in my back, so the breaks were a good way to relax a bit while practicing.” (TE8-M). Furthermore, one participant also stated that controlling one’s focus of attention helped in being attentive to bodily sensations: “I really focused on something in my body and not just different focus in music. That helps a lot because then I’m a bit less tense in my body.” (TE5-I). Finally, the use of imagery was mentioned as a useful way to practice without physical strain: “I think it is also important because you can prevent yourself from being too physically involved.” (E3-M).As a final theme, some participants – although mentioned least frequently – felt that the intervention helped in having more Group interactions were stimulated during the intervention: “I really liked that you brought people together and you talked about mental aspects and fears everyone has. It also helps to see that people have shared issues” (TE4-P). This group sharing might have helped in exchanging personal experiences, as well as alleviating some of the taboo on sharing information about individual practice time, which some participants believed to exist:In addition to their general experiences, participants also mentioned several specific aspects they found beneficial during the intervention. First, most participants appreciated the way I)I thought that by interacting with each other you are keeping it more alive. So for that reason I think it has a lot of added value, that everybody is not doing it independently of each other, but that you are doing it with your colleagues at the same time. That way you can also talk about it. Because otherwise there also rests a little bit of a taboo on what you are doing at home. That is something you normally don’t talk about. It was nice because there was this structure in kind of scientific approach to it, which is missing a lot in music education in general. So, that was nice, because then you had some guidance and tools on how to do it and what to do and what not to do. That was nice. (TE3-E). Although the practical nature of the workshops was appreciated, several participants also argued even more exercises could have been included.Participants also appreciated how these scientific principles were translated into practical exercises during the workshops: “I liked the fact that the things we were talking about, that we were right away experiencing them and trying these things out. And to share the point of view with the other academists and the mentors.” ;Thirdly, participants highlighted the importance of the I)I really found the telephone calls very nice. I found them very inspiring and stimulating. It is actually very nice when someone is looking over your shoulder. Not like you had [four] workshops and then it is just “off you go.” (E5-I). These sentiments were shared by all E musicians. However, in line with the quantitative evaluations, the TE group seemed to be somewhat more critical of the monitoring sessions. Although most still perceived these sessions to be positive, the TE group also considered them to be an additional time constraint.In addition to motivate participants to use the proposed principles, participants also appreciated the opportunity to ask questions and discuss challenges in applying the intervention principles, during the monitoring sessions: “I thought it was very nice that I could ask things and that we could discuss a number of things and search for solutions.” . This might partially explain why the intervention as a whole was perceived less valuable by the TE musicians. Consequently, some participants argued that the included strategies should also be taught to music students: “I really think it’s perfect to give things like these [workshops] for conservatory students, because the things I already did, I learned partially from teachers” (TE7-I). Indeed, two E musicians stated that they began using these principles with their own students.A number of challenges as well as potential avenues for improvement in the way the intervention was implemented, were mentioned by the participants. First, some participants argued that the intervention provided Time constraints experienced by the participants. Although the intervention principles were designed to make practice more efficient, participants argued that learning and incorporating them might actually require additional time: “I have the idea that it [Goal-setting] consumes more time. I know that it can save time, but it still feels like an extra addition while studying.” (E3-I). Especially the TE musicians frequently mentioned that due to their busy schedules, they lacked the time to try out these principles: “I had to prepare a two hours programme over the weekend, so I had no time to change my study routine.” (TE4-M);A second theme reflecting intervention challenges were the I)Sometimes it felt that I preferred my own methods and not to try experimenting so much. But this kind of study will probably be very good for somebody who is in an Easter break of Christmas break or something where he can experiment I think. ;If you can find a way to involve them [mentors] more. I think it was really nice that they were there actually, I just really liked it. Because you feel like, of course it’s a workshop and we are learning, but the fact that they are there too, we don’t feel like a student. We have a different level of course, they are professionals that are still learning, but it is nice that there’s not only students. (TE8-I)Maybe it helps to work also closer together with the mentors. [During the workshops] we shared a lot of experiences and that really helped me also. Because of course they played for so long and had a lot of beautiful experiences which really helps. . Consequently, the TE group suggested involving performance psychologists with a specific background in music: “It would have been nice if a musician would be on your team. This person could have explained it more in musical terms or slightly different to make it more understandable” (TE2-I). Notably, E participants did not consider this different background a hindrance and some even found it enriching: “It didn’t bother me that you had a background in sports. It didn’t make it less clear to us or made us question why these methods applied to us.” (E3-I); “I actually quite liked it that the [background] was different, but that it was still possible to have a conversation and an exchange of advice” (E5-I).A fourth theme reflecting intervention challenges were the participants’ views on the Nature of music as art. A limited number of participants believed that due to the very specific nature of music and music-playing as an art form, certain principles from other performance domains, such as goal setting, could not directly be translated or adapted:Fifth, another perceived challenge related to the I);In a way [goal-setting] doesn’t always work for musicians, since it is an art form. I find it almost impossible to make goals measurable. And since technique and musical ideas are often so deeply connected, sometimes we don’t want to practice too specific. (TE5-I)I don’t know, maybe in sports or other things, or science in general, you can break things down much easier. In music sometimes, well, if we guys tell you that we are focusing on technique or on music, you maybe take it literally actually. We are focusing on everything, but a bit more in this direction. Everything is quite unified, and you can’t just separate things. ;I’m not planning to use the planned disruptions and what-if scenarios that quickly again. Those are things that you’ll use when you’re nervous or doing auditions. At least, that is what I think. So, I won’t use it that soon again. (E7-I)I can imagine that it is more applicable when you have an important recital, audition or exam. These are key moments in which you go through one particular door, stand on one particular stage and have one particular situation. It will be more concrete in these situations.  by collaborating in close relationship with the respected teachers and the existing culture; allowing the teacher to be the messenger of certain information. This also lines up with the transitioning elite musicians’ calls for the active inclusion of their mentors within the present intervention.Finally, cultural factors should also be considered when translating performance psychology principles to the context of music. This was exemplified by the background of the researchers being perceived as a barrier. Furthermore, a number of participants believed certain principles were difficult to apply because of the artistic nature of music making. Nevertheless, research has demonstrated the value of these performance psychology principles for musicians . As suchA number of limitations and avenues for future research should be recognized when discussing the findings of this study. First, only a limited number of participants were involved, which might limit broad statistical inferences. Although we recognize this is an important limitation, it should be noted that the statistical trends were consistent with the in-depth qualitative data gained throughout the intervention. It has been argued that such a triangulation of different data sources provides the best approach to gain an in-depth and contextualized understanding of a specific phenomenon . NeverthPerformance psychology can provide an important added value for high-level classical musicians’ development and performance. Building on previous work with music students, the present process evaluation study provides preliminary support for the usefulness of a performance psychology intervention for transitioning elite and elite musicians. At the same time, a number of contextual considerations became evident when implementing this intervention within these specific populations. This information can be used by performance psychology practitioners and music educators looking to optimize future interventions for musicians of different levels of expertise.The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by Vaste Commissie Wetenschap en Ethiek van de Faculteit der Gedrags- en Bewegingswetenschappen (VCWE), Vrije Universiteit Amsterdam. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.JK and RO jointly designed and implemented the intervention presented in the current study. The data collection and data analysis was conducted primarily by JK, with RO acting as a critical friend and supervisor. JK produced the first draft of the manuscript, with RO providing extensive feedback.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The aim of this systematic review was to analyze the types of human chewing simulator described in scientific literature. in vitro”; “dental materials”; “shear strength”; “fatigue fracture”; “bite force”; “prosthetic materials”; “chewing simulator”; “chewing machine”; “simulated mastication”; and “dental wear simulator.” Two researchers worked independently to assess the titles and abstracts of the articles. The quality of the in vitro trials selected was evaluated by means of the Consolidated Standards of Reporting Trials scale. An electronic search was conducted in the databases PubMed, Embase and Scopus. The search strategy included 10 search terms: “The electronic search identified 80 articles related to the topic of interest. After reading the full texts, ten works were selected. The articles focused mainly on the design of chewing simulators. Most of them were considered of moderate quality. Regarding the characteristics that an ideal chewing simulator should encompass, the devices described in articles varied greatly in terms of movement, periodontal ligament simulation, force sensors, and the materials tested. No chewing simulator offers all the characteristics necessary to reproduce human masticatory movements and forces under the humidity and pH conditions of the oral cavity. A simulator that encompasses all these characteristics would make it possible to standardize trials involving simulated mastication. Key words:In vitro, dental materials, dental wear simulator. The mechanical properties of the materials used in dentistry must be thoroughly tested under laboratory conditions before they can enter clinical use. Trials of mechanical resistance  must be complemented by wear and fatigue testing.Wear means “to damage, erode, or destroy by friction or use,” while fatigue means “weakness in metal or other materials caused by repeated variations of stress.” In dentistry the usual terms used to describe these scenarios are aging and fatigue  has established a series of directives for good laboratory practice. But to date, no single standardized system has been determined for measuring wear and aging, as is the case when measuring traction and fracture resistance. In the currently available chewing simulators, variability in terms of the control and regulation of forces impacts negatively on the reproducibility and variability of results, and the difficulty of extrapolating l cavity .The aim of the present systematic review was to analyze the types of chewing simulator described in scientific literature.in vitro studies.This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) . It coulin vitro mastication; C = analysis; and O = human mastication.The review’s PICO  question was: Which chewing simulator most resembles human mastication, in which P= chewing simulators; I = in vitro wear resulting from the action of chewing simulators. Inclusion criteria were: chewing device design was described, and test samples were described (teeth studied/antagonist teeth). These criteria were chosen to center the review on articles involving chewing simulation and oral conditions.The search identified articles that analyzed in vitro”; “dental materials”; “shear strength”; “fatigue fracture”; “bite force”; “prosthetic materials”; “chewing simulator”; “chewing machine”; “simulated mastication”; and “dental wear simulator”. Boolean operators (“OR” and “AND”) were applied to link search terms to the research question  to assess the titles and abstracts of the articles identified in the initial search. The following variables were recorded for each article: author and year of publication, device, study teeth/antagonist teeth, simulated mastication movement, force sensors.in vitro studies included in analysis, their quality was evaluated by means of the Consolidated Standards of Reporting Trials (CONSORT) scale, modified to assess the quality of in vitro trials of dental materials  of load sensors for measuring the forces exerted. Seven articles stated the force applied. Conserva et al.  used a b , made from materials that exhibit resilient rather than rigid behavior. In this context, silicon and acrylic resin have been used to imitate periodontal ligament and alveolar bone, respectively .The simulator must be able to generate movements that imitate human mastication as far as a machine is able to. In mastication, the mandible moves in vertical and horizontal direction, making a bidirectional motion ,17. HoweIf wear testing is to be standardized and obtain comparable results, it is essential for the magnitude of forces generated by chewing simulators to be controlled to create specific test conditions, and for these to be identical for each specimen tested. For this reason, the simulator must be equipped with load sensors to record the loads applied, as in some of the studies reviewed ,8,11-14.In vitro studies may use human saliva or de-ionized water, among other liquids, as a lubricant or even as an abrasive/erosive medium (To simulate conditions in the oral medium, some studies have attended to environmental factors such as humidity/wetness, temperature and pH, which can also influence the mechanical properties and behavior of dental materials in the mouth. The body acts as a heat pump that maintains the temperature in the oral cavity at 37ºC. Teeth and any restoration material are continuously bathed in saliva with a pH of around 7. Humidity in the cavity is 100%. However, the introduction of different foods in the mouth can alter environmental conditions to a large degree, causing fluctuations in pH and temperature. An artificial oral environment should be able to reproduce normal conditions in the oral cavity, and to manage the temperature and pH fluctuations that may occur. e medium ,13,15,18et al. (There are few bibliographic references regarding the design of models for use in chewing simulators for trials involving simulated mastication. Several parameters have not been sufficiently investigated, including the curve of Spee and the curve of Wilson. Alemzadeh et al.  analyzedin vitro study that was the subject of the review. The search did not include the Cochrane database as it does not admit in vitro research. The quality of most of the studies was moderate as it is hard for this type of in vitro research to meet the criteria that would deem it of high quality.The present systematic review suffered certain limitations. Despite conducting a search in the databases, only a small number of relevant articles were identified, which might be explained by the difficulties involved in carrying out the type of The present systematic review did not identify any chewing simulator that includes all the characteristics that would make it possible for complete upper and lower dental arches to reproduce the movements of human mastication under the actual humidity and pH conditions in the oral cavity. There is need for a simulator that meets all these requirements in order to standardize future trials involving simulated mastication.


Dear editor,We read with interest of the article by Lukas Schuierer and colleagues  about thFirst, why and in whom does high load HSV replication detected in mechanically ventilated patients and should be considered as a causative pathogen? Bruynseels et al.  found thSecond, how should we monitor HSV load in patients with MV? In Schuierer’s study , only onFinally, in Schuierer’s report , the treReinhard Hoffmann, Lukas SchuiererWe thank Drs. Wang and He for their careful evaluation of our paper. First, we agree that detectable herpes simplex virus (HSV) replication is not a rare event in ventilated intensive care unit (ICU) patients . We, howSecond, as stated above, we do not think that sequential monitoring of patients without clinical evidence of infection is helpful. Moreover, it is not entirely clear to us which type of “blood tests” the authors suggest. In our experience, serum or full blood PCR testing may be performed additionally to the testing of respiratory secretions and would underscore its clinical significance, if positive. We have, however, never really evaluated the diagnostic value of HSV PCR in blood samples—after all, it can be detected in almost 30% of sepsis patients . SerologTheir final point is related to the first point above—we evaluated only patients with a high likelihood of viral disease before initiation of treatment. Moreover, our result that acyclovir is effective in these patients suggests—a posteriori—that HSV may be the responsible pathogen for pulmonary disease.Sincerely,Reinhard HoffmannLukas Schuierer


Understanding representations of disease in various art genres provides insights into how patients and health care providers view the diseases. It can also be used to enhance patient care and stimulate patient self-management.This paper reviews how cardiovascular diseases are represented in novels, films, and paintings: myocardial infarction, aneurysm, hypertension, stroke, heart transplantation, Marfan’s disease, congestive heart failure. Various search systems and definitions were used to help identify sources of representations of different cardiovascular diseases. The representations of the different diseases were considered separately. The Common Sense Model was used a theoretical model to outline illness perceptions and self-management in the various identified novels, films, and paintings.Myocardial infarction followed by stroke were the most frequently detailed diseases in all three art genres. This reflects their higher prevalence. Representations ranged from biomedical details through to social and psychological consequences of the diseases.Artistic representations of cardiovascular diseases reflect cognitions, emotions, and images of prevalent disease. These representations shape views and behaviour of ill and healthy persons regarding heart diseases. As these representations are amenable to change, they deserve further research, which may be instrumental in improving the quality of life of persons struck by cardiovascular diseases. Changing illness perceptions appears to be a method to improve self-management and thereby quality of life in patients with various cardiovascular diseases. Illness representations tell viewers and readers about the images of illness – they inform us about the narratives patients construct and communicate. Cardiovascular diseases are the most prevalent cause of morbidity and mortality in most societies. Treatment and management of these conditions draw upon biomedical knowledge. However, social and behavioural factors are also involved in the etiology and course of most if not all these diseases. Smoking tobacco, excess alcohol intake, lack of physical activity, vital exhaustion, and social inequality are examples of these factors, illustrating how illness is more than just disease . StudyinExpressions of disease in various art forms reflect societal views of the image of illness. Von Engelhardt has reviewed how various diseases have been represented in novels ; Ostherrwww.medhum.med.nyu.edu] was searched, using the search terms ‘myocardial infarction’, ‘aneurysm’, ‘hypertension’, ‘stroke’, ‘heart transplantation’, ‘Marfan’, and ‘congestive heart failure’. These terms were combined with the categories ‘novels’, ‘films’, and ‘paintings’.The website from New York Columbia University Medical Humanities  “he had to throw up, his hand was shaking, his pupils were rigid and wide, his left arm shocked with tremors ... “(p. 27) … he watched his hand in horror, he felt as if it was a strange being, independent and excited, a being that did not acknowledge his control (p. 15) … don’t you see how much I struggle to say the most necessary, what makes you look at me so horrified ... I see the horror and anxiety on your face … (p. 30) … he realized that he suffered the most by knowing that he could not express himself towards another” (p. 133).La Toccatina [The light touch] by Pirandello. As detailed by Van Haaren et al., the image of stroke some 100 years ago reflects societal views about illness and its consequences [The impact of a stroke on the social existence of the sufferer is illustrated in equences . In the The abyss including details of his recovery [Written after my death for his autopathography. He died a few years following the stroke [Several autopathographies on stroke are available as well. Taylor, a neuroanatomist, wrote about her “major haemorrhage, due to an undiagnosed congenital malformation of the blood vessels in my head” (p. 1) . She wrorecovery . The othe stroke .Amour, the relative stability and happiness of a married couple are destroyed by the stroke that hits the wife [Amour impresses in her depiction of the functional effects , and of the psychological , and social consequences . In the second film, Flawless, the protagonist is a retired firefighter in New York City, single, who suffered a heart attack - his physician however, talks about a stroke [Two films depict the functional, psychological, and social consequences of stroke. In the wife . The fila stroke . Robert Mend the heart Maylis de Kerangal follows the life of the donor of the heart – a 18-year-old victim of a car crash – and the receiver of the heart, and the roles of a number of persons between donor and receiver [Two novels are devoted to heart transplantation, both in French. In receiver . De KeraL'Intrus (The Intruder), the author J.L. Nancy is the recipient of a heart himself. In a short story format, some 16 pages, the author philosophizes about the meaning of the donor and the donor heart in his life [In his life . “… my sJohn Q a successful heart transplantation is demonstrated in a desperate father’s child, whose insurance would not cover the transplantation [In antation . TherefoCalne, a transplant surgeon, published a collection of paintings and drawings by himself, documenting the transplantation of hearts, kidney and livers  Fig. 3)3). His pA tale of the ragged mountains tells the story of Mr. Augustus Bedloe – “who was peculiar in his personal appearance” – (p. 208) ["He was singularly tall and thin. He stooped much. His limbs were exceedingly long and emaciated. His forehead was broad and low. His complexion was absolutely bloodless. His mouth was large and flexible, and his teeth were more wildly uneven. ... His eyes of a cat ... they were abnormally large and round like those of a cat...their ordinary condition was so totally vapid, filmy and dull, as to convey the idea of the eyes of a long-interred corpse." (p. 1).It is unclear whether Poe had special knowledge of Marfan’s disease, or whether Poe knew people with the disease. In any case, Poe’s words are unique: they introduce Marfan’s disease into world literature.Edgar Allan Poe in (p. 208) . A remarMo the protagonist, who is born with clubbed feet, is diagnosed with Marfan’s syndrome in his adolescence [In lescence . The movAgosta der Flügelmensch und Rascha die schwarze Taube by Christan Schad is a spectacular depiction of Marfan’s disease  and a p“It’s his heart, … he has to be careful. He had to give up his practice and everything. … Each summer I think it will be the last time; that’ we shan’t see him again. But each May I get the message from him, the reservation.” (p. 169) - Dr. Martino by William Faulkner describes the illness history of a physician in the South of the USA, who suffers from congestive heart failure.A recent study on the medical history of Bocaccio, author of the Decameron, maintains that the author suffered heart failure. The paper contains a painting of Bocaccio, suggestive, according to the authors, of heart failure .BMJ), Journal of the American Medical Association (JAMA), Lancet) have niches on ‘patient narratives’. No such journal exists in the cardiology domain.Cardiovascular disorders are the major cause of mortality in highly industrialized societies. The morbidity, societal and financial impact are also major. These considerations contrast remarkably with the rather modest attention to these diseases in various art genres. It is not immediately clear what the background of this finding might be. In oncology, a somewhat different situation seems to be observable: various scientific journals devote substantial attention to the representation of cancer and suffering from cancer in novels, film, painting, and music. General medical journals  in patients and their caregivers and health care providers, seem worthwhile research areas .Our select review of how patients with various cardiovascular disorders make sense of their illness, as represented in novels, films and paintings, points at starting points for clinical interventions. After all, addressing maladaptive ways of making sense of the illness, which lead to maladaptive coping and self-management and poor outcome should result in more adaptive coping, self-management and a positive outcome. Empirical studies do indeed support this line of reasoning. Broadbent et al. in their systematic review and meta-analysis of illness perceptions report that illness perceptions “were able to predict some outcomes up to one-year follow-up” ( p. 1361)The almost prototypical intervention study in the area of patients with cardiovascular disease and illness perceptions is the study by Petrie et al. . In a ra


Although a large body of information exists relating to cellular therapies, much of this information is either anecdotal or has been obtained from relatively small clinical trials, so that the level of evidence available to direct adoption of therapeutic approaches is quite limited. Despite this, a large number of clinics offer various cellular treatments without having gone through the processes of FDA approval. Florida is considered a “hotspot” of such sites, with a large number of clinics relative to the population.To better understand the magnitude and scope of this issue with a specific focus on cardiovascular disease, we surveyed clinics in Florida advertising “cell therapy for heart failure”. We identified only 8 clinics that “treat cardiac conditions, including heart failure.” Data on administration route, cell type used, dose, success rate, cost, and training of persons performing procedures were collected when available, via email, telephone, or website information.A total of 20,135 patients were identified as treated: 2157 for cardiac conditions. All clinics reported administering cells intravenously, using either adipose- or umbilical-derived sources. Doses ranged from 30 to 150 million cells per treatment. The “success rate” ranged from 65 to 85%, with costs from $6000 to $20,700. Procedures were performed by PAs, MDs, and DOs.Large numbers of patients  have been and presumably are still are being treated for “cardiac conditions.” We conclude that implementation of uniform data collection with an outcome registry, as well as creation of a public database listing FDA-approved cell-based clinical trials, would be useful to patients and the cardiovascular field at large. Cell-based therapy is gaining momentum as an increasing number of promising, but preliminary, results are presented. With some positive, yet early results, and potential applications across many disease states, clinicians and patients are eager for cell therapy to be incorporated into “standard treatment.” However, like any new treatment, there are many experimental, regulatory, and practical hurdles before sufficient evidence is gathered for this to occur. Despite the fact that this slow, but crucial process is based on a long-standing public health precedent, many clinicians and patients are not prepared to delay. Related to this, a plethora of direct-to-consumer (DTC) outpatient clinics have opened in the United States offering cell-based therapies with uncertain regulatory status, meaning that the cellular products offered are not provided in the context of an IND or IDE. After discussion with a range of leaders in the field, we have termed these clinics “Clinics of Uncertain Regulatory Status” (COURS), and the treatments offered without IND or IDE as “Treatments of Uncertain Regulatory Status” (TOURS).One potentially important target for cell-based therapies offered by COURS, which is the focus of this communication, is heart failure and other cardiac conditions. In the US, heart failure has a prevalence of 6.2 million and is anticipated to increase 46% between 2012 and 2030, with a predicted prevalence of > 8 million in 2030. In 2014, there were 1 million new cases in those > 55 years old [Despite an incomplete understanding surrounding cell therapy for heart failure, there are a large number of COURS around the U.S. offering some form of it to patients . This trCurrent regulatory involvement by the FDA includes guidance that contradicts claims that these COURS are compliant or exempt from compliance. In 2017 the FDA gave clinics offering cell therapy 3 years of “enforcement discretion”. It was indicated that regulations will be enforced more stringently, but not until November 2020, to give COURS time to learn about FDA regulatory pathways and ensure compliance .Considering the prevalence of COURS and their potential for lack of benefit or even possible harm, there is a clear need for clinical data to better understand the products and procedures being used. Turner and Knoepfler  surveyedGoogle searches were conducted using the following phrases: “stem cell therapy Florida”, “stem cell clinics Florida”, “stem cell treatment Florida”, “stem cell for heart Florida”, and “stem cell heart failure treatment Florida”. An initial scan of the first 20 pages of results for each search produced 109 websites appearing to be distinct sites offering cell-based treatment. The sample was further narrowed by visiting each of these websites to ensure it met our sample criteria. With exclusion of broken links, companies that did not perform clinical procedures, clinics operating outside of Florida, and clinics that didn’t actually offer cell-based treatments, the sample was reduced to 76 websites. Then each of these websites were thoroughly perused to determine if treatment for heart failure was mentioned. This resulted in only 8 clinics claiming to treat cardiac conditions; of these, 4 clinics explicitly advertised the treatment on their website and the other 4 did not explicitly list conditions they treated, but confirmed treatment of cardiac conditions via follow-up phone call.From among this selected group of 8 clinics, we attempted to collect the following data: total number of patients treated, number of patients treated for cardiac conditions, route of administration, type of stem cell, dose, success rate, cost, type of personnel performing procedure, frequency of adverse events, publications, academic affiliation, and their understanding of the status of FDA compliance. Initially, we attempted to find these data on clinic websites. Then, we made phone calls and emails to the clinics to ask any remaining questions. It was not possible to collect some data because of lack of information or refusal to answer.A total of 20,135 patients were reported as treated with cellular therapeutics across the Florida clinic sites we surveyed; 2157 of these were treated for “cardiac conditions.” All clinics reported that they employed intravenous administration for cardiac indications. They noted using either adipose (7 clinics) or umbilical-derived (4 clinics) sources, with 3 clinics offering both. The estimated doses administered ranged from 30 million to 1 billion cells per treatment, according to 4 clinics that had the information available. The reported “success rate” ranged from 65 to 85% from the 2 clinics that had these data available. Neither clinic could elaborate on how they defined or measured success. The reported price to patients ranged from $6000 to $20,700 for 7 clinics willing to provide these data. The mean price for therapy utilizing adipose tissue-derived cells was $7742 (6 clinics) while the price for umbilical cord tissue-derived products was $12,162 (4 clinics). The mean price across 7 clinics was $9593, while the median price was $6500. By multiplying the median price by the total number of patients treated for cardiac conditions, we estimate that > 14 million dollars were spent by these patients receiving cell therapy for heart failure or associated cardiac conditions.Cell harvesting and administration were performed by PAs, MDs, and DOs specializing in surgery, internal medicine, or pain management, with only one clinic reporting presence of a “cardiac specialist” and another clinic reporting presence of a “stem cell scientist.”Adverse events were reported as none (3 clinics) or described as few (4 clinics): one clinic reported occurrence of flu-like symptoms after cord blood, which was rectified by switching to a Wharton’s jelly product; another clinic simply reported adverse events rates as < 1%; another reported one adverse event related to the injection itself; and one clinic reported 2 cases of “pseudo-sepsis.”Publications related to their stem cell treatments were reported by 3 of 8 clinics. One clinic reported having a previous partnership with an academic institution, one was “working on” a future academic partnership, and a third had a doctor who is a clinical professor at a local institution. All clinics claimed to either be “in compliance” with FDA regulations or “exempt” from FDA regulations entirely. One clinic stated treatment is legal under “right to try,” another said “stem cells are not drugs and therefore are not under FDA regulations,” another cited their compliance “as indicated by only treating diseases with significant clinical evidence,” another said they “follow FDA procedures for sterility and handling of cells,” another specifically cited “compliance via the same surgical procedure exception of 21 CFR 1271,” and 2 others simply said that they were “compliant,” but provided no further explanation.The questions presented to the clinics and the questions that were answered are summarized in Table The US Food and Drug Administration (FDA) is responsible for regulating cell-based therapy as tissue and tissue products, under the broader category of vaccines, blood, and biologics. The use of bone marrow and umbilical cord blood-derived stem cell preparations has historically been permitted by FDA to treat hematopoietic system disorders, including cancers such as leukemia and other disorders ; but mos“We support sound, scientific research and regulation of cell-based regenerative medicine, and the FDA has advanced a comprehensive policy framework to promote the approval of regenerative medicine products. But at the same time, the FDA will continue to take enforcement actions against clinics that abuse the trust of patients and endanger their health with inadequate manufacturing conditions or by purporting to have treatments that are being manufactured and used in ways that make them drugs under the existing law but have not been proven safe or effective for any use.”In 2017, FDA released 4 guidance documents providing clarification of regulations, which imply that the large majority of these COURS are not compliant. Following this, the FDA sent “regulatory correspondence” to at least 46 clinics and has pursued legal action against two stem cell clinics . FDA ComSeveral publications have detailed adverse aspects related to the unregulated field of cell-based therapy including severe vision loss, infection and even death –14. UnrePrevious reports highlight “sensationalism” within the field and how COURS use it to recruit patients by advertising sweeping, potentially hyperbolic efficacy claims while minimizing potential risks , 16.COURS offering cell therapy have been known to cite Right to Try (RTT) legislation as a justification for operating outside of the FDA. The Right to Try Act, formally known as the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act, was signed in May of 2018 to allow patients meeting certain criteria to be able to access experimental treatments. Eligible patients must have a life-threatening condition, have exhausted approved treatments, and be unable to enroll in a clinical trial as certified by a qualified physician. Eligible investigational drugs must have completed a Phase 1 safety trial, have not already been approved by the FDA for any use, and have an IND application which has been filed with the FDA. With the limited information provided by COURS, it is not possible to determine whether they are truly practicing under this law as it is intended. Heart failure is certainly a life-threatening condition, however, it is not known whether particular COURS ensure that each patient being treated has been certified by a physician to be unable to enroll in a clinical trial and has exhausted current treatment options.Additionally, it is unclear whether patients are providing reasonable informed consent. Informed consent requires not only a detailed outline of the risks and benefits of the procedure but also a statement on the evidence available, or lack thereof (as is relevant with many cell therapies). Lysaght et al. addressed the legal standpoint that a person can only consent to medical intervention when it is substantiated by a tangible benefit, implying that any treatment without evidence of therapeutic benefit cannot be consented to .An unexpected consequence of receiving these stem cell therapy treatments at COURS is that such treatment often excludes the patient from clinical trials designed to gather scientific evidence. The patient may not be made aware of this outcome. Furthermore, the costs can render patients less able to pay for or have their insurance cover standard-of-care treatments of proven benefit for their heart failure . This noThese issues highlight potential damage COURS can inflict on both individual patients as well as the cell therapy field. Despite these concerns, the large number of “success stories” relayed from patients should not, and cannot, be ignored. A considerable number of clinics advertise patient testimonials on their websites and many claim to have received relief, which, for those with chronic life-altering conditions, can be a major improvement in quality of life. Future regulation can help ensure that patients receiving credible treatment are permitted to continue to do so, while at the same time investigating clinics that may be unsafe. The goal should be to halt procedures that are not pursuing evidence supporting safety and efficacy, while facilitating the study and ultimate provision of therapies and procedures that are based upon sound scientific evidence.With 8 million Americans seeking medical advice online every day, Liska et al. emphasized the importance of educating patients to prevent misinformation, maintaining open relationships between patients and their primary care physicians, and formation of a Stem Cells Ethics Consortium . They noOthers have called for even more involvement from physicians, including combating a perceived “era of misinformation” by challenging sweeping marketing messages provided by COURS. Additionally, they call for involvement of state medical boards to set guidelines for what is and is not appropriate and to sanction members  when demonstrating unprofessional conduct .Guidelines for the Clinical Translation of Stem Cells [The International Society for Stem Cell Research (ISSCR) created a task force to develop em Cells . These gem Cells .Knoepfler proposed that dubious clinics could be identified by a lack of affiliation with academic institutions, few publications, and no investigational new drug (IND) or investigational device exemption (IDE) application . While iThis is an initial effort to collect data important to better understand “cell-based therapies in the field”. We observed that despite Florida being the third largest state in population and being identified as a “hotspot” of COURS, it was possible to identify only a small number of locations that actually treated heart failure patients. This suggests that most COURS avoid these high-risk patients. Going forward, we document the need for instruments to uniformly collect these data.We acknowledge a number of limitations to our study. It is likely that these data underestimate the actual number of clinics in Florida that offer cell therapy for heart failure, since there may be clinics that treat heart failure but do not advertise it. Accordingly, it is not possible to confirm that our sample included all of the providers who treat heart failure in a COURS. Thus, our work should be viewed as the beginning of an effort to better define and assess the use of cell-based therapy for cardiovascular disease. Additionally, we recognize that the lack of information related to patient history, including specific diagnoses concerning the nature of the “heart failure”  or “cardiac conditions” available from the clinics limits the analysis of our data. This is in part related to the common reliance on patient testimonials rather than objective benchmarks or patient-reported outcomes gathered in a pre-specified manner. Finally, we make no statement on credibility of any clinics presented at this time.While reasonable primary goals would be to promote safety and scientific innovation concurrently, it is imperative that steps be taken to ensure these aims are being considered. With these goals in mind, possible recommendations include the following:First, we recommend movement as quickly as feasible into IDE and IND-based trials, in conjunction with strongly advised participation in outcomes registries, to allow data collection on safety and patient outcomes and, ultimately, evaluation of treatment approaches. We estimate > $14 million have been spent in treatment of heart failure at COURS, in Florida alone, without data collection. If this money had been used to fund clinical trials with uniform data collection, it is likely that selected cardiac indications would be closer to approval for marketing. It is not only imperative that patients shift from COURS to FDA-approved clinical trials, but it is important that data accumulated from FDA-approved clinical trials can be synthesized in such a way that facilitates the progression of the regulatory process.Second, we advocate standardized protocols for cell processing and administration for COURS as they elect to transition to IDE/IND-based trials, thus becoming Clinics with FDA-Approved Regulatory Status (CARS). Simply collecting data from COURS is not sufficient; these data need to be obtained as uniformly as possibly to permit them to be analyzed collectively. However, this becomes difficult when procedures and products are widely varied. Thus, efforts to arrive at consensus on protocols not only for elements such as cell harvesting and administration, but also for outcome measures and general data collection would minimize this barrier. We suggest that it would be useful to employ a designation for providers who adhere to such standardized protocols, such as a certification or compliance notice.Lastly, a practical and readily implemented approach should include creation of a user-friendly database available to the public, allowing patients to access a list of cell-based trials with FDA clearance via IDE or IND. This would assist patients in readily locating CARS rather than COURS to best ensure safety and efficacy, as well as encouraging patients to receive experimental therapies along with data collection in a manner that advances the field and ultimately good patient care.Large numbers of patients have received cell-based therapies for “cardiac conditions” in settings with uncertain regulatory status, but information about results is limited. Implementation of uniform data collection with an outcome registry and a public database of FDA-approved cell-based clinical trials would be useful to patients and the cardiovascular field.


This Special Issue concerns recent developments of a theory for energy conversion on the nanoscale, namely nanothermodynamics. The theory applies to porous media, small surfaces, clusters or fluids under confinement. There are a large number of unsolved issues in these contexts and present efforts only paint part of the broader picture. We may still ask questions on how far down in scale we can really use the Gibbs equation. Which theory can replace the Gibbs equation beyond the thermodynamic limit? It is well known that confinement can change the equation of the state of a fluid, but how does confinement change the equilibrium conditions? How do we formulate equilibrium conditions on the nanoscale, and what are the independent variables? To deal with equilibrium alone seems a formidable task, let alone how to extend the descriptions to systems away from equilibrium.This Special Issue explores in more detail some roads that were opened by Hill when he launched his thermodynamics for small systems in 1963. His method has, however, not gained much attention since it was published. We now consider this an underused opportunity. The theoretical developments in nanothechnology need to follow the experimental progress, and that is rapid. It is our ambition, therefore, to aspire to an increased effort that can further develop suitable theoretical tools and methods in nanoscience. All ten contributions to this Special Issue can be seen as efforts to support, enhance and validate such theoretical developments.The first two papers ,2 demonsThe next three papers ,4,5 concA Legendre–Fenchel Transform for Molecular Stretching Energies” that an alternative for small systems lies in the Legendre–Fenchel transform. This is an extension of Hill’s theory that may prove useful in practice. Strøm et al. [When Thermodynamic Properties of Adsorbent Films Depends on Size” offers a new way to deal with adsorption on, say, atmospheric particles. In yet another article, Strøm et al. [The issue contains three extensions of Hill’s theory, see papers ,7,8. HilStatistical Mechanics at Strong Coupling: A Bridge between Landsberg’s Energy Levels and Hill’s Nanothermodynamics”. They review and show the connection between three theories, including Hill’s, proposed for the thermodynamic treatment of systems that do not obey the additivity ansatz of classical thermodynamics.The last two papers ,10 are s


This is the case of a 30-year-old pregnant female who presented to the medical emergency department with signs and symptoms consistent with a psychotic episode. At the time of presentation, the patient was noted to have paranoia and delusions focused on her current pregnancy. On further evaluation in the emergency department, the patient’s urine toxicology was found to be positive for methamphetamines. Following medical clearance, the patient was admitted for acute inpatient psychiatric stabilization. During hospitalization, her psychosis rapidly resolved with only the use of two emergency treatment injections containing antipsychotic medication. This case presents an interesting differential diagnosis between a brief psychotic disorder with peripartum onset and a substance-induced psychosis, and allows for further discussion in the differentiation and clinical treatment of these diagnoses.  According to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition DSM-5, 2013), disorders with abnormalities including hallucinations, disorganized speech, disorganized, abnormal or catatonic behavior, and negative symptoms such as flat affect, poverty of speech, and anhedonia are classified as schizophrenia spectrum and other psychotic disorders. Subtypes exist to better classify each disorder in terms of symptom content, episode frequency, time of onset, and other factors [3, disordLike many psychiatric disorders, a combination of biopsychosocial factors contributes to peripartum disorders. It is believed that these disorders may be associated with abnormalities in maternal neurotransmitters, alterations in estrogen levels due to pregnancy, hypothalamic-pituitary-adrenal axis dysfunction, and thyroid dysfunction, along with genetic predisposition . Still, In addition to organic psychiatric disorders, acute intoxication and withdrawal from substances can also present with psychotic symptoms. The treatment of psychotic symptoms often requires careful analysis and differentiation between primary psychotic disorders and substance-induced psychoses, the latter of which tend to resolve once the substance is out of the system. This is a case of a pregnant, G5P3A2, 30-year-old female with no clear past psychiatric history who presented to the medical emergency room requesting removal of her unborn child, stating it “was a devil snake inside of her, she can feel it moving and wants it out.” The patient presented alone and voluntarily to the medical emergency department (ED) where she was noted to be acutely psychotic, disorganized, noncooperative, and with delusions focused on her unborn child. Per chart review, family history was noncontributory. The patient was hemodynamically stable, and physical exam was within normal limits. Laboratory examination was grossly unremarkable except for urine toxicology, which was positive for amphetamines. At this time, the patient was unable to elaborate regarding substance use given her clinical condition and chart review did not reveal a history of amphetamine use. In the ED, ultrasound was completed that demonstrated a healthy 27-week fetus. During evaluation by the internist and obstetrician, the patient remained verbally aggressive and combative, requiring emergency medication due to risk of harm to self and others. Haloperidol 5 mg, lorazepam 1 mg, and diphenhydramine 50 mg were administered via intravenous (IV) push. The patient was placed on an involuntary hold for psychiatric evaluation and remained with a 1:1 sitter for safety until medical workup was completed and the patient could be transferred to the behavioral health emergency department. Of note, based on review of the patient’s electronic medical record, she had last been evaluated approximately five weeks prior for routine obstetric care, at which time she was calm, cooperative, and noted without changes in mood or perceptual disturbances. Following medical clearance, the patient was transferred to the behavioral health ED. Upon presentation, the patient was noted to be somnolent and unable to engage in meaningful interview secondary to administration of medication in the medical emergency department. Upon further psychiatric evaluation, the patient continued with the above-mentioned psychotic symptoms and, due to risk of harm to self and others, she admitted involuntarily to acute inpatient psychiatry. On the first day of admission, the patient was noted to be isolative with limited interaction with staff and peers on the inpatient unit. On initial interview with the primary inpatient psychiatric treatment team, the patient was alert and oriented to self and time but disoriented to place. She was irritable, disorganized, and noted to be a poor historian. The patient continued to perseverate on the need for removal of her unborn fetus, stating that “the snake was biting her and causing a current to run through her body.” The patient endorsed command auditory hallucinations to “remove the snake”; she was distractible throughout the interview and appeared to be responding to internal stimuli. She also endorsed visual hallucinations of a male figure whom she was “unable to catch.” She demonstrated poor insight into her condition and continued to represent a risk to self and others; psychiatric hospitalization was thus continued under involuntary status. Later that night, the patient again became acutely agitated, threatening staff on the unit and attempting to elope. Despite multiple attempts at redirection and verbal de-escalation, the patient continued to present acute risk of harm to self and others, requiring emergency medication. Haloperidol 5 mg and diphenhydramine 50 mg, the same medications that had been administered in the emergency department, were administered intramuscularly (IM). Following medication administration, the patient was able to sleep through the night with no further issues. The following morning, the patient’s demeanor had changed. She was notably less irritable and was superficially cooperative on interview with the primary psychiatric treatment team. The patient denied stating she thought the baby was a snake, reporting instead that it “just felt like a snake,” However, her desire to gain discharge was apparent, as she asked questions such as, “What else do I need to say to leave?” Shortly after the interview, the patient was observed attempting to elope from the inpatient unit while verbally and physically threatening unit staff. Another emergency treatment dose of haloperidol 5 mg and diphenhydramine 50 mg was administered IM. Given the continued episodes of unsafe behavior requiring emergency medication and the patient’s continued poor insight and judgment, she continued to present a risk of harm to herself and others, requiring further hospitalization. On interview the following day, the patient’s psychosis appeared to have improved significantly. She was calm, cooperative, with linear and logical thinking. She no longer fixated on being pregnant with a snake and was able to recognize and verbalize that she was pregnant with a healthy fetus. Upon further discussion regarding her positive urine toxicology from admission, the patient reported that she had abstained from substances of abuse for “many months,” but relapsed the night prior to admission. She attributed her presentation of bizarre behavior and acute psychosis to her substance use and stated that her symptoms had now resolved. The patient was goal-directed and future-thinking, reporting wanting to be with her family for the remainder of pregnancy and at time of childbirth. At that time she was counseled regarding substance use, particularly during pregnancy, and expressed understanding. She denied other substance use history during pregnancy and declined to elaborate on amphetamine use prior to presentation, stating it was a "one time incident." She did not require any further emergency treatment throughout her admission and continued to deny thoughts of harm to self or others, including the baby; she also stated she planned to remain abstinent from substances of abuse after discharge. The patient was discharged after a six-night admission with follow-up appointments with an obstetrician and psychiatrist, as well as referrals and resources for substance abuse. While pregnancy is a positive experience for many mothers, for some it can be dangerous. In addition to the physical challenges that pregnancy places on a woman’s body, it also increases a woman’s susceptibility to a variety of psychiatric conditions. These may include postpartum blues, peri- and postpartum depression, and brief psychotic disorder with peripartum onset . The lasAdditionally, prepartum psychosis is much less common, and much less studied, than postpartum psychosis . In 1990The other diagnosis that one must consider in any psychotic patient, pregnant or not, with recent history of drug use is SIPD. The DSM-5 definition of SIPD requires the presence of delusions and/or hallucinations while or soon after an individual uses a substance capable of producing such psychotic symptoms . ImportaMany studies have demonstrated the ability of amphetamines to trigger acute psychosis in a variety of patient cohorts, from healthy individuals to regular users of amphetamines ,11,12. AAdditionally, much research has demonstrated that patients with primary psychotic disorders are at greater risk for substance abuse, including amphetamines . Even fuThis makes the patient’s diagnosis all the more challenging. This is a patient who may have had an underlying psychiatric illness that predisposed her to psychosis in the setting of substance abuse, regardless of her current pregnancy. She also may have had undisclosed amphetamine-induced psychosis in the past that resurfaced during pregnancy, an obvious physiological stressor. Other diagnostic possibilities in this case include a peripartum psychotic episode that rapidly resolved with administration of three doses of psychotropic medication or a combination of multiple biopsychosocial factors leading to an acute psychotic episode. This case presents an opportunity for interesting discussions regarding overlapping psychiatric presentations and the role of substances and pregnancy in the manifestation of psychiatric disorders.The presentation of psychosis in the peripartum period presents an interesting and often challenging diagnostic picture. Brief psychotic disorder with peripartum onset may be an independent disorder, but rarely presents in patients with no past psychiatric history. Rather, most patients presenting with this condition have underlying psychotic disorders, such as bipolar disorder, schizoaffective disorder, or schizophrenia. The picture is further complicated when the mother is using substances of abuse, which themselves can lead to a substance-induced psychosis. Ultimately, the goal in any patient presenting with psychotic symptoms is to ensure the safety of the patient and those around them, such as the fetus in pregnant patients, regardless of the final diagnosis.There is an extreme lack of studies and information on prepartum psychosis, substance use in pregnancy, and psychiatric disorders in pregnancy in general. This makes an already complex differential diagnosis even more challenging. Future research in psychotic disorders during pregnancy, especially those complicated by substance use, is needed and will continue to improve patient care and outcomes.


Medical education is currently more considerate about the human dimension. The present qualitative study aimed to explain the experiences of clinical professors with regard to humanism in clinical education in Iran.This mixed methods study had two phases, a quanitative phase of scientometrics and a qualitative phase of a content analysis. In the scientometrics phase, Ravar PreMap and VOSviewer software programs were utilized for plotting the conceptual networks. The networks were analyzed at the micro-level based on centrality indices . The conceptual network was plotted and the prominent topics in clinical education were identified using co-word analysis. In the second qualitative phase on the topic, based on the scientometrics phase, semi-structured interviews were conducted with clinical professors. The interviews were transcribed verbatim and analyzed.humanism with the frequency of 137 had the highest rate (97.753), closeness (97.802), and betweenness (13.407). Moreover, from the interview data analysis, two themes of “intertwined nature of the human spirit in clinical education” and “humanistic behavior of professors in clinical education” were extracted.On the basis of the analysis of titles, abstracts, and keywords of the retrieved articles on clinical education from ISI Web of Science, Scopus, and PubMed, 1412 keywords were extracted. After the refining process, 356 keywords with 6741 relations remained. Upon plotting the conceptual network, 19 conceptual clusters related to clinical education were obtained. Then, micro-level network analysis  indicated that the keyword As a part of the educational culture, humanistic values must be intertwined with the medical education curriculum. In this regard, humanism and clinical reasoning are the two major clusters of clinical teaching; moreover, altruism and adherence to humanistic values, and scientific qualification are other main pillars that should be considered as the criteria for the selection of clinical professors and medical students. The networks were analyzed at the micro-level based on centrality criteria  [Searches were limited to the fields of titles, keywords, and abstracts. Ravar PreMap  , 16. Cloeenness) . Degree eenness) , 16.The data retrieved from the databases were transferred to Excel in order to determine the overlapping articles and to delete duplicates. Then, to determine co-occurrence of the words, as well as merging and standardizing of the keywords, they were entered into Ravar PreMap to identify keywords with a high frequency to filter the words, and thus to select the most relevant ones. This was done in five steps: 1) merging singulars and plurals of the words, 2) re-writing abbreviations in the complete form, 3) eliminating keywords with a general meaning and no semantic load standardized synonyms, and 4) converting specific keywords into general keywords, and 5) deleted numbers or keywords such as %, #, &, >. The MeSH list was used to select general keywords and the most frequently used synonyms of the words. Words were separately standardized by two researchers and finalized upon consensus. The co-word analysis method was adopted in order to plot the conceptual network and identify the prominent topics in clinical education, which is a content analysis method aiming to identify the map of science and major topics in different domains of science . To thisThe second phase of the study involved qualitative conventional content analysis. In this phase, purposive sampling, continued by theoretical sampling were used. The data were collected from the key participants with rich experiences about the topic. Semi-structured interviews were conducted with selected clinical professors some of which had Education Development Center (EDC) management experience in Shahid Beheshti, Tabriz, Isfahan, Shiraz, Mashhad, Mazandaran, and Guilan Universities of Medical Sciences. A list of guided questions was designed to cover all relevant topics. However, the interview questions were not fixed, and the interviews were guided and probed according to the issues emerged from the interaction between the interviewer and the interviewees. More, the relevance of questions to the objectives of the study was taken into account. Before starting the interviews, an information sheet was presented to the study participants, and the study objectives, voluntary participation, and confidentiality of the data were emphasized. Afterwards, their informed consent was secured, and the interviews were conducted and recorded. After the interview sessions, each interview was transcribed verbatim and analyzed to identify key humanistic attitudes of clinical educators. Then, the data were carefully read and re-read for several times and the first-level coding with an emphasis on the manifest and implied content was extracted by identifying and highlighting the units of analysis, namely sentences and paragraphs. A code was allocated to each unit of analysis. Subsequently, the codes were classified based on their scope and attributes into sub-categories and categories. The codes were repeatedly checked and contradictions were resolved by discussion. To determine the validity of the data, repeated examination of data and simultaneous analysis were performed. The extracted codes were examined by the participants and their acceptability was ensured. The research team reached a consensus on the extracted codes and thus confirmed the process of data analysis. Moreover, immersion was performed upon continuous long-term involvement with the data. To ensure transferability, the details of the study were carefully documented and the steps were explained in details in order to allow the external audit.The search strategy identified 3939 articles. After removal of duplicates in the databases and the assessment of title and abstracts, 1229 articles were included into the scientometrics analysis.PRISMA flowchart of articles selection1412 keywords resulted from the analysis of the titles, abstracts, and keywords of the articles on clinical education retrieved from PubMed, Scopus, Web of Science databases, using the Ravar PreMed. After the refinement process, 356 keywords with 6741 relations remained. The keywords with minimum frequency (1 and 2) were discarded. Next, using VOSviewer, content analysis was performed, yielding 19 conceptual clusters in the domain of clinical education , the keyword humanism with the frequency of 137 had the highest degree (97.753), closeness (97.802), and betweenness (13.407). Ten keywords with maximum frequency, betweenness, and degree are presented in Table Semi-structured interviews were conducted with 27 clinical professors . Four participants were full professors, while 26 were associate professors. Based on the analysis of the interviews, two themes of “intertwined nature of the human spirit in clinical education” and “humanistic behavior of professors in clinical education” were extracted.In the theme “intertwined nature of the human spirit in clinical education”, two categories of “humanistic values in clinical education” and “patient as the axis for clinical education” were extracted Table . For thepatient who matters, not the disease.”In the category of “patient as the axis of clinical education”, Participant 1 remarked, “Patients are noble. If they do not cooperate with us, we could not teach our students anything.” Participant 13 said: “The patient is our educational content. Each patient is unique, with unique characteristics. Two people may have the same disease, but the same treatment cannot be selected for both of them. The student must observe that it is the In the theme “Paying attention to human dignity of patients”, “Respecting patient rights”, “Creating a sense of empathy with patients”, “Not making patients anxious”, and “inculcating a sense of priority of treatment over education” were identified. Table . In the If, for example, the patient is a young girl, she may feel uncomfortable, and so we must not allow students to examine her.” According to Participant 3, “Sometimes patients prefer to consult us directly. In our field, we have patients with psychiatric diseases who may not cooperate with us. In these cases, we must play the role of consultant by ourselves. Participant 15 said: “Several patients may be in the same room. When we examine one of them, we must draw the curtain so that he/she would not be uncomfortable. The patient may not want other patients to hear him/her. We must be careful with these issues.” In the category “creating a sense of empathy with the patients”, Participant 5 said: “You see sadness and loneliness in a patient’s face. If you greet them and ask about their health and tell them that you are there for them and there is no need to worry, you can give them hope. The students observe your behavior.” Participant 17 remarked: “When doing the rounds, the patients’ next of kin is usually asked to leave the ward. Some patients cannot take care of themselves. I tell my students, ‘If you see that patients need help, help them. Take their hands. If they want to take their medicine, give them a glass of water’. These actions gain their trust and ensure their cooperation.” According to Participant 12, “Sometimes a patient has to be hospitalized an extra day for getting the results of a test. I sign the discharge form and tell them to ask someone else to get the results and take them to me the next day. Patients have families who are worried about them. Therefore, I speed up their discharge process so that they can go back to their families.”In the category “inculcating a sense of priority of treatment over education”, Participant 15 mentioned: “I always tell my students that the patients are always right, even if they get mad or don’t let you examine them. Respect them; they are under no obligation to be a scenario for your education. Their treatment comes first.” According to Participant 16, “Some people think that we can use patients as a scenario for education in any way they desire and that students are allowed to examine them as many times as they want. However, patients are under no such obligation. The students can examine them only if they allow them to.” Participant 9 said: “Some patients feel that teaching hospitals view them as clinical scenarios, and their treatment does not come first. I tell my students to follow up the patients and ensure them of this follow-up. Occasionally I call the imaging center when the student is present and follow up the patient CT scan. The students realize that the doctor is responsible for the patient follow-up, and the patient peace assures that his/her treatment is moving forward.” As for the theme “taking care not to worry the patients”, Participant 10 said: “The Internet has recently become another stressor for patients. When we discuss the disease in the presence of the patients, they check the new terminology they hear, which may not even be related to their disease. I always try to postpone extra discussions with students to the end of the rounds at the corridor or in the class.”The present study aimed to explore the experiences of clinical professors with regard to the critical topic of humanism and humanistic behavior in clinical education settings, for which two themes of “intertwined nature of the human spirit in clinical education” and “humanistic behavior of clinical professors” were extracted.In the theme “intertwined nature of the human spirit in clinical education”, two categories of “humanistic values in clinical education” and “patient as the axis for clinical education” were extracted. In the majority of studies, medicine has been regarded as a science and an art and it has been explained that professionalism cannot be attained through mere medical knowledge . Today, Deliberate or inadvertent denial of intrinsic values of patients, threatens their human dignity, and leads to their non-cooperation, ineffective communication, which deteriorates humanistic encounters with patients. According to Spiro, an “unseen and unheard patient” shows that we face the problem of “de-humanization” and must re-humanize medicine .In the theme “humanistic behavior of professors in clinical education”, five categories of “Paying attention to human dignity of patients”, “Respecting patient rights”, “Creating a sense of empathy with patients”, “Not making patients anxious”, and “inculcating a sense of priority of treatment over education” were extracted.Respecting human dignity of the patients can be summarized in the saying “Do unto others as you would have them do unto you” . Paying The quality of clinical care is influenced by humanitarianism and job satisfaction. Research has shown that doctors with a higher degree of empathy with patients have had higher job satisfaction and fewer clinical errors which lead to lawsuits . MoreoveAnother category was respecting rights of patients in clinical education. Patients demand respect for their privacy, values, and expectations and do not wish to be viewed as educational scenarios or subjects of study. Unfortunately, in most studies on patient rights, patients were dissatisfied with repeated examinations, the doctors and the healthcare team who do not introduce themselves, and lack of respect for their privacy , for exaIn Iranian teaching hospitals, the healthcare team believes that patients who consented to receive treatment from students or residents are educational scenarios, while this is against the charter of patients’ rights; the educational encounter with patients requires their permission  and undeHumanitarian values in clinical settings are mostly transferred to students through role modeling position of professors and the hidden curriculum , 35–37. The curriculum of medicine must highlight humanistic values which form the student professional identity, and respectful encounter with the patients must be recognized as a norm in medicine. It is essential to commit doctors and medical students on spending ample time with patients, listening to them carefully, being sensitive to their emotional states, and regarding humanistic beliefs as the spirit governing their professional activity. Medical boards have an obligation to regard humanistic elements as an important component of clinical competency, because physicians should incorporate attitudes that value the patient as a human being.We acknowledge that the small sample in this qualitative study may not be plentifully representative of the clinical teachers in undergraduate medical education in Iran. However, to increase the diversity of participants, medical faculties and EDC managers from across the country were interviewed to reach maximum variation and to resolve the inconsistencies.