Natural language processing (NLP) is central to the communication with machines and among ourselves, and NLP research field has long sought to produce human‐quality language. Identification of informative criteria for measuring NLP‐produced language quality will support development of ever‐better NLP tools. The authors hypothesize that mentalizing network neural activity may be used to distinguish NLP‐produced language from human‐produced language, even for cases where human judges cannot subjectively distinguish the language source. Using the social chatbots Google Meena in English and Microsoft XiaoIce in Chinese to generate NLP‐produced language, behavioral tests which reveal that variance of personality perceived from chatbot chats is larger than for human chats are conducted, suggesting that chatbot language usage patterns are not stable. Using an identity rating task with functional magnetic resonance imaging, neuroimaging analyses which reveal distinct patterns of brain activity in the mentalizing network including the DMPFC and rTPJ in response to chatbot versus human chats that cannot be distinguished subjectively are conducted. This study illustrates a promising empirical basis for measuring the quality of NLP‐produced language: adding a judge's implicit perception as an additional criterion. The study reveals that the subjectively undetectable differences between natural language processing (NLP)‐produced and human‐produced language are detected by the mentalizing network, which illustrates a promising empirical basis for measuring (and thus engineering) ever‐higher quality NLP‐produced language: adding a judge's neural activity as a criterion when assessing and optimizing NLP. Extensive ongoing efforts in NLP research have been made to produce human‐quality language. Although huge advances have been achieved, there are nontrivial challenges in methods to assess the quality of NLP‐produced texts.Language is central to all aspects of social communication in humans, and the research field of natural language processing (NLP) encompasses computational techniques for learning, understanding and producing human language content.1 Ther[–] However, it is highly conspicuous that very few published studies have considered the assessment criteria for language quality for the judge who assesses the quality of NLP‐produced texts. To our understanding, the current assessment is to use self‐reporting as the criterion of judgment.[–] Traditionally, researchers have relied on self‐report measures to assess a person's demographic information, beliefs, and feelings. However, self‐report measures are subjective and insensitive. For example, it is known that when assessing sensitive issues such as racial discrimination, contraception use and sexual orientation, self‐report measures are subject to both recall bias and social desirability bias. Furthermore, self‐report measures are insensitive and consequently not suited to assess appraisals of ambiguous situations, automatic attention bias, and reflexive psychopathological symptoms. Thus, the new assessment criteria for judging may involve the implicit measures that are commonly considered objective and relatively sensitive.Extant studies on NLP have focused on developing or improving the ability of programs to interpret and respond meaningfully to human language.–4  supporting that language encodes information relevant to fields including personality, social, clinical and cognitive psychology, and it is thought that the social and psychological functions of language are processed by a reader or listener mainly at a low or implicit level. Thus, implicit perception might be highly informative for measuring the quality of NLP‐produced language.Psycholinguistics research has demonstrated that the language we use in our daily lives can reveal aspects of our social and psychological worlds,17 sup Researchers analyzed a large body of text samples taken from journal abstracts, college writing assignments, and diaries across days and even years, and detected good internal consistency (across text types) for dozens of linguistic dimensions. Another study sampled students’ natural conversations and showed a relative stability of linguistic features across context: there were no significant linguistic difference effects when language was assessed in the diverse contexts, including home versus public places, workplaces versus coffee shops and direct personal interactions versus phone interactions. Although language use is stable within an individual, individuals differ in the ways they talk and write. Even when the content of the message is the same, individuals express themselves with their own distinctive styles. Language usage patterns have been recognized as stamps of individual identity. Of note, individual differences in language usage patterns have been demonstrated as related to individual differences in personality traits.Psycholinguistic evidence has shown that a person's language usage patterns are stable across time and context.,19 NLP‐produced language is typically generated by retrieval‐based or generation‐based approaches, with both approaches modeling language over very large datasets based on language materials from different sources and people. An NLP system's verbal response to a user's utterance already exists in the training datasets, and is selected by algorithms. Thus, the NLP system's responses are derived from multiple people, suggesting the consequence that NLP‐produced language represents multiple personalities. In the last decade, models that can learn to control the style and usage patterns in language generation have been proposed,[–] which has almost certainly improved the perceived quality of NLP‐produced language. However, the NLP systems have as‐yet not reached the ability to produce language with language usage patterns as stable as humans. Thus, we hypothesize that the variance of personality perceived from NLP‐produced language is larger than that from human‐produced language.In contrast, the language usage patterns of NLP systems might be unstable. Designing NLP systems with consistent personality—reflected by stable and consistent language usage patterns or language style—is a reported approach for establishing an emotional connection with users, although this remains a large challenge.22 NLP Therefore, we propose that adding neural activity data from a judge who assesses the quality of NLP‐produced texts as an implicit index to the assessment criteria for language quality could substantially improve our ability to reliably determine whether the NLP‐produced language achieves the human quality.Neural activity data is more sensitive to the processes of psychological cognition than behavioral data.,28 People perceive the social competence of non‐human agents based on aspects such as personality, physical attributes, and emotional traits. Specific to the NLP systems, the social competence inferred from their produced language can contribute to establishing an emotional connection with users. During a conversation, people can purposefully and automatically infer others’ mental states, even with virtual agents’, which has been shown to engage the mentalizing network.Social competence, defined as the ability to interact effectively with others while reaching personal goals, has been conceptualized as “effectiveness” in social interactions.29 Peo The reported neural basis of mentalizing  includes the temporoparietal junction (TPJ) and the medial prefrontal cortex, among other regions. Understanding the communicative intent of an utterance requires the mentalizing network to be invoked to progress from coded meaning to speaker meaning. It has been proposed that people do not adopt an equally intentional stance toward robots, computers, and other artificial agents as compared to humans. In previous studies, the stronger activation in the mentalizing network has been repeatedly found when interacting with a human compared to a computer or a robot.[–] Therefore, we hypothesize that NLP‐produced language results in distinct neural activity in the mentalizing network as compared to human‐produced language.Mentalizing, a fundamental component of human social cognition, describes the process by which we understand the assumed inner thoughts and intentions of others by observing or imagining others’ actions, speech, facial expressions, etc.33 The whereas the NLP systems have not yet reached the capacity to produce language with stable language usage patterns. Previous studies have also reported that relatively stronger activation in the mentalizing network can be detected when a human participant is interacting with a human as compared to interacting with a computer or a robot,[–] suggesting that NLP‐produced language may result in differential neural activity in the mentalizing network.Previous evidence has shown that a person's language usage patterns are stable across context,,19 Twenty participants were recruited to evaluate the personalities of the respondent of each chat based on the Big Five Inventory. We calculated the variance of each of the five personality dimensions  for each chat and compared the variance between chat categories . To replicate the result, we also collected chatbot chats from another chatbot named as XiaoIce, a Chinese social chatbot designed by Microsoft. Then we used identity rating tasks , the left temporoparietal junction (lTPJ), the dorsomedial prefrontal cortex (DMPFC) and the ventromedial prefrontal cortex (VMPFC) .,42] Figure . Finally22.1p = 0.01).To test the possibility that personality perceived from the chatbot chats was not stable across context, 8 chatbot chats produced by Meena, an English social chatbot developed by Google, and 8 human chats produced by different individuals were obtained. All the chatbot and human chats were obtained in continuous, free conversation. The personalities of the respondent of each chat were evaluated by 20 participants, all of whose mother tongue or official language is English, based on the Big Five Inventory. We calculated the variance of each of the five personality dimensions  for each chat (8 human and 8 chatbot chats) and compared the variance between chat categories  using permutation tests. The results showed that the variance of the agreeableness dimension perceived from chatbot chats was larger than that of human chats .To replicate the larger variance of perceived personality from chatbot chats, we also collected chats from another chatbot named as XiaoIce, a Chinese social chatbot designed by Microsoft. we collected 42 human chats and 42 chatbot chats and then recruited 165 independent participants to evaluate the personalities of the respondents for these chats based on the Big Five Inventory ; note that all of the participants for evaluation are native Chinese speakers. We calculated the variance of each personality dimension for each chat and compared the variance between chat categories  using permutation tests. Briefly, the results showed that the variance of the neuroticism, agreeableness, conscientiousness, and openness dimensions perceived from chatbot chats was larger than that from human chats  . The activation value of each chat was assessed by a general linear model (GLM) and used for multi‐voxel pattern analysis  according to a previous meta‐analysis study of the mentalizing network , but not for the lTPJ  or the VMPFC .We first determined whether the activity patterns could classify real identities between the chat categories . The mean classification accuracy for real identities was above the permutation‐based significance level for the DMPFC , the rTPJ  or the lTPJ .We next determined whether the activity patterns could classify rated identities between the chat categories . The mean classification accuracy for rated identities was above the permutation‐based significance level for the VMPFC .Our results indicate that the activity patterns of the DMPFC and the rTPJ can be used to informatively classify the real identities of chats . Some may argue that the classification accuracies were mainly contributed by subjectively distinguishable human and chatbot chats , rather than by subjectively indistinguishable human and chatbot chats . We, therefore, examined whether the activity patterns of the DMPFC and rTPJ could still be used to classify real identities between subjectively indistinguishable human and chatbot chats . The mean classification accuracy for real identities between subjectively indistinguishable human and chatbot chats was still above the permutation‐based significance level for the DMPFC . The rTPJ similarity matrix indicated that there also was similar activity between HRC and HRH . These results indicate that chats produced by a specific generator (human or chatbot) elicit similar activities in the DMPFC and rTPJ across subjects, regardless of the identity judgments. No significant differences were detected in the lTPJ matrix  by using an across‐subject correlation. The purpose of this analysis was to determine whether specific pairs of chat categories reveal similar activity across subjects. We averaged the activation value for each chat category and extracted the average activation value of each ROI. We calculated the similarity matrices within ROIs by calculating the correlation between all pairs of chat categories across subjects. The DMPFC similarity matrix indicated that there was similar activity between HRC and HRH  separately across the whole brain. For the real identity classification, pattern classification was robust in the rTPJ and the DMPFC . There were 2.49 ± 1.62 chats rated as “Chatbot” (identity rating score ≤ 2).p = 0.0068; Figure p = 0.0008), but not for the rTPJ  or the VMPFC .We first determined whether the activity patterns could classify real identities between the chat categories . The mean classification accuracy for real identities was above the permutation‐based significance level for the DMPFC , but not for the DMPFC  or the rTPJ . Note that correlation analyses indicated no significant correlations between classification accuracies and identity rating score differences for any ROIs.We next determined whether the activity patterns could be used to classify rated identities between the chat categories . The mean classification accuracy for rated identities was above the permutation‐based significance level for the VMPFC . Owing to the limited number of chatbot chats, we did not perform across‐subject similarity correlation analysis.We then determined whether the activity patterns of the DMPFC and rTPJ could still be used to classify real identities between subjectively indistinguishable human and chatbot chats . The mean classification accuracy for real identities between subjectively indistinguishable human and chatbot chats was still above the permutation‐based significance level for the DMPFC  for the real identity classification. For the rated identity classification, pattern classification was robust in no regions.We performed the same exploratory whole‐brain searchlight analysis as described above for the English version of the identity rating task to identify brain regions encoding category‐specific information in each identity classification  separately across the whole brain. Pattern classification was robust in the left precentral gyrus , the lTPJ , or the VMPFC . The mean classification accuracy for rated identities was not above the permutation‐based significance level for any ROIs .The mean classification accuracy for real identities was above the permutation‐based significance level for the rTPJ  elicited similar activity in the DMPFC and rTPJ across subjects regardless of the identity judgments. The comprehensions of the speaker's meaning are more than the retrieval of word meaning or sentence‐level, which requires the mentalizing network. Mentalizing describes the cognitive activities through which we infer the inner thoughts and intentions of others. To judge the identity of “Participant B” in the identity rating task, the participant needs to retrieve language and then infer both meaning and social information. Mentalizing establishes the context that enables insight into the identity of the mind of “Participant B”, leading to a better understanding of the respondent. Early investigations into the neural basis of mentalizing observed a typical network of activation, which included the medial prefrontal cortex and TPJ. Various mentalizing tasks consistently activate the medial prefrontal cortex and TPJ. The right TPJ is implicated in mental‐state reasoning, that is, thinking about other people's beliefs, emotions and desires. Activation in the right TPJ has been also shown to associate with autistic spectrum disorder syndrome severity in a self‐other mental‐state reasoning task. The DMPFC has been implicated in a process known as continuous internal monitoring. Conflict monitoring and error monitoring are also thought to depend on some underlying processes instantiated in the DMPFC. We interpret our results to indicate that, for the subjectively indistinguishable chatbot chats, participants may continuously evaluate the unapparent mismatches between chatbot and human by inferring interacting partner's beliefs, emotions and desires in the mentalizing network. Our neuroimaging results demonstrate that neural activity in the mentalizing network can be used to distinguish NLP‐produced language from human‐produced language, even when these cannot be distinguished subjectively.Speaker meaning is the intended meaning a speaker wants to communicate with a specific utterance.46 The A meta‐analysis of 243 retest coefficients for personality traits showed that the average observed value after an interval of 15 years would be ≈0.60 (correlations more than 0.50 are large based on Cohen's rule of thumb). Using writing samples of college students, researchers found reliable effects for Big Five personality dimensions on word choice. It also bears emphasis that the previous work has established that people's language usage patterns satisfy the basic psychometric requirements of consistency across context and stability across time. Therefore, the personality perceived from the language materials of a given person should be stable. However, recall that current NLP methods are based on the modeling of language from very large datasets comprising language materials produced by many different people. As a consequence, NLP‐produced language inherently represents multiple personalities, suggesting that the language usage patterns of NLP are not stable and not consistent across context. Our data support that the participants did not subjectively detect any aberrant changes in some but not all of the NLP usage patterns. However, we show that this aberrant change was reliably detectable based on neural activity in the mentalizing network.It is possible that the neural activity patterns we detected in the mentalizing network could be due to the change in usage patterns of NLP. Recall our initial findings showing that chatbot chats exhibit a larger variance of perceived personality compared to human chats (in dimensions including agreeableness and neuroticism). To our understanding, personality traits represent a reliable and stable way of indexing an individual's thinking, feeling, and behavior. Hundreds of studies using different methods, instruments, and populations have consistently found high levels of retest stability for personality traits over intervals of up to 40 years.55 A m Measures are best done when combining self‐report with other information, such as an individual's physiological or neural data. This “multi‐method” assessment might provide more accurate data of the subject.Our results support that adding neural activity as an additional criterion would produce more precise and comprehensive information when measuring the quality of NLP‐produced language. We show that subjectively undetectably subtle differences between NLP‐produced and human‐produced language are detected in the mentalizing network; iterative testing and incorporation of experimental insights could dramatically advance progress in the development of NLP and perhaps other fields of artificial intelligence. In psychology, a self‐report is any measure or survey that relies on an individual's report of his/her behaviors, attitudes, beliefs, or symptoms. It can yield much valuable information. Most experts in psychological research and diagnosis suggest that self‐report should not be used alone because of its limitations.60 Mea[–] pointing to a link between thinking about oneself and thinking about others. Judging a chat as human‐produced might prompt the judge to make inferences about the human's characteristics, beliefs and/or mental state, which might trigger self‐referential processing as mediated by the VMPFC.Our results revealed that a separate circuit in the mentalizing network is responsible for processing subjectively rated identities between chatbot and human. Our results found that the activity patterns could be used to classify rated identities between the chat categories . Furthermore, chats rated as “Human” elicited similar activity in the VMPFC across subjects. That is to say, regardless of the real identity (chatbot or human) of “Participant B”, chats identified as human‐produced induced similar activity in the VMPFC. The VMPFC has been implicated in self‐referential judgments,–634Identification of informative criteria for measuring NLP‐produced language quality can support the development of ever‐better NLP tools. The present study provides empirical evidence that the usage patterns of NLP‐produced language are not stable across different subjects of conversations and shows that this instability results in distinct patterns of mentalizing network activity between NLP‐produced and human‐produced language. Our study contributes to the field of NLP by showing that endowing a dialogue system with particular personality traits is essential to deliver more human‐like conversations. Another contribution is that our study successfully applies neuroimaging technology to the field of artificial intelligence for assessing the NLP‐produced language quality. Future studies might explore the feasibility of adding neural activity data as an implicit index to the assessment criteria for standard Turing tests. Besides, the relationship between the judge's language ability and neural activity sensitivity should be clarified in the future with the large sample size and the real‐time communication just like standard Turing tests.In the identity rating task, participants read the chat contents and gave an identity rating score for the chat interlocutor, and this did allow the classification of subjectively indistinguishable chatbot chats and human chats. Provided access to sufficiently sensitive neuroimaging instruments can be obtained, it would be fascinating to determine if our findings about implicit perception differences can be replicated in a standard Turing test. We anticipate that adding a judge's implicit perception data could become a standard criterion for conducting Turing tests.Concerning study limitations, the sample size for our fMRI analysis was small, in part owing to limited access and long set‐up times for fMRI technology. Naturally, this limits the statistical power of our analyses; ideally, a cheap‐to‐produce and easy‐to‐use, yet suitably sensitive apparatus for monitoring the relevant brain regions  would substantially expand the use of neuroimaging and implicit perception differences for assessing NLP‐produced language. Another limitation was the somewhat homogenous population of humans used to generate the human chat content for the second of the two identity rating tasks we examined in this study: high‐school girls, aged 15–19. This was expanded in the first experiment (based on human chat content from randomly selected humans), but there is still a gap in the scope of the materials used to train the examined XiaoIce and Meena versus the scope of the human materials. Thus, caution is warranted regarding any interpretations around topics beyond simply distinguishing machine versus human .5d = 0.5). Doing a power analysis using G*power suggested a sample size of 27 for 0.8 power. The study was approved by the Research Ethics Committee of the University of Science and Technology of China (NO. 2020‐N(H)‐099), and written informed consent was obtained from all participants, consistent with the Declaration of Helsinki. The methods were carried out in accordance with the approved guidelines.Thirty‐six participants whose mother tongue or official language is English  were recruited to complete the identity rating task. Data from 6 participants were excluded because of excessive head motion  with motion exceeding 0.3 mm was censored; participants who had more than 15% of their TRs censored were excluded from further analysis), data from 3 participants were excluded because they failed to complete the task, yielding an effective sample size of 27 participants . Fifty‐five participants were recruited to perform the Chinese version of the identity rating task. Among them, 2 participants were excluded due to equipment malfunction; 4 participants were excluded due to excessive head motion during fMRI. The final sample comprised 49 participants . Forty‐nine participants were recruited to complete the reading task. Data from 3 participants were excluded because of excessive head motion, yielding an effective sample size of 46 participants . The sample size was determined using a medium effect size , an English social chatbot designed by Google, and conversations with randomly selected human respondents . Volunteers conversed (by text) 1:1 with Meena or a person; the content of the conversations was varied, including for example topics like hobbies, weather and sports, among others. During the collection of chat materials, the content of the conversation was unlimited and could be changed freely. A conversation was required to last at least 7 rounds (with the longest lasting 14 rounds). Eight conversations with Meena and 8 conversations with humans which had similar numbers of conversation rounds  and total words  were chosen.In the identity rating task, chatbot and human chats were provided by the Brain Team of Google Research42 andIn the Chinese version of the identity rating task, 2 chatbot chats were produced by XiaoIce, a Chinese social chatbot designed by Microsoft, and 6 human chats were produced by different persons. The details of the assessment of chat materials are shown in the Supporting Information: production process of chat materials for the Chinese version of the identity rating task.The personalities of the “Participant B” for each of the 16 chat materials  were evaluated by 20 participants according to the Big Five Inventory (see the details in Supporting Information). To test the hypothesis that the variance of personality perceived from chatbot chats was larger than that from human chats, the variance of each of the five dimensions for each chat  was calculated and the variance between chat categories using permutation tests was compared.https://rec.ustc.edu.cn/share/85b13e20‐dd9e‐11ec‐ade7‐0d670f3af599.The identity rating task consisted of four fMRI runs, each run comprising four chats. Participants were required to judge 16 chats (8 human chats and 8 chatbot chats) and informed that each chat contains several conversation rounds between “Participant A” and “Participant B”; the “Participant A” in each chat was a human and the “Participant B” was either a human or a chatbot, and they needed to judge the identity of “Participant B” based on the content of each chat. In the identity rating task, a conversation round between “Participant A” and “Participant B” was presented in the center of the screen to a participant for 4 s; this was done one by one, with a variable interval . After each conversation round in a chat was presented, all conversation rounds were presented simultaneously following a 20 s interval. Subsequently, the identity rating judgment posed the following question: is “Participant B” in this chat a chatbot or a human being? . To visualize the presentation of the identity rating task, a video demo is available at In the Chinese version of the identity rating task, each fMRI run comprised two chats. The experiment followed the same procedures above.The experimental procedure of the reading task was almost the same as that of the Chinese version of the identity rating task  covering the whole brain was used to acquire the functional MR images. High‐resolution T1‐weighted spin‐echo imaging data were also acquired for anatomical overlays and 3D gradient echo‐planar imaging for stereotaxic transformations after functional scanning. Before entering the scanner, participants were instructed to keep their heads still during all scans. During the identity rating task, four functional scan runs occurred, with each lasting 512 s. During the Chinese version of the identity rating task, four functional scan runs occurred, with each lasting 424 s.Gradient echo‐planar imaging data were acquired using a 3.0 T GE discovery MR750 with a circularly polarized head coil, at the Medical Image Center, University of Science and Technology of China. A T2*‐weighted echo‐planar imaging sequence  with 33 axial slices . Time series preprocessing was done using AFNI software. A general linear model (GLM) was used to identify neural responses exhibiting correlations with each chat material. In each chat, the regressors were as below: first reading stage: the period when a conversation round was presented one‐by‐one; second reading stage: the period when all conversation round were presented at the same time; and interval: the period between the first and second reading stages. These regressors were convolved with a hemodynamic response function (HRF) and simultaneously regressed against the blood oxygenation level‐dependent (BOLD) signal in each voxel. Six regressors for the head motion were also included. The β values for each chat's first reading stage were used for MVPA.Functional data were realigned to the lowest motion volume. The realigned images were normalized to the MNI standard space template with a resolution of 2 mm to test whether patterns of brain activity  could classify the identities of chats. For the real identity classification, chats produced by volunteers were labeled as “Human”, and chats produced by chatbot were labeled as “Chatbot.” For the rated identity classification, chats with an identity rating score ≥ 3 were labeled as “Rated‐as‐Human”, and chats with an identity rating score ≤ 2 were labeled as “Rated‐as‐Chatbot.” The discriminability of patterns for the two categories within‐subject in each identity classification  was tested separately with CoSMoMVPA using the linear support vector machine (SVM) tool. Classification training and testing were done using a leave‐one‐chunk‐out cross‐validation strategy.The authors used MVPA44 to β values for the chat's first reading stage to balance the number of each chat category before the MVPA were averaged. Due to the limited number of chatbot chats in the Chinese version of the identity rating task, data from some participants did not meet the minimum number of all chat categories for the MVPA. Finally, data from 37 of 49 participants were assessed for the rated identity classification; data from 11 of 49 participants were assessed for classifying the real identities between subjectively indistinguishable human and chatbot chats. A similar situation occurred in the reading task. Data from 37 of 46 participants were assessed for the rated identity classification; data from 10 of 46 participants were assessed for classifying the real identities between subjectively indistinguishable human and chatbot chats.Due to the unbalanced number of human and chatbot chats in the Chinese version of the identity rating task, the x = 56, y = −54, z = 26; left TPJ: x = −52, y = −58, z = 24; DMPFC: x = 0, y = 58, z = 12; VMPFC: x = 0, y = 52, z = −8). The β value of each ROI was extracted and was applied to MVPA. Statistical significance of the classification accuracies for ROIs was determined using a permutation test that generates a set of 5000 chance classification accuracies by permuting the labels each time.4 ROIs that were defined in a previous meta‐analysis study of the mentalizing network were here used. The coordinates of these ROIs calculated from a meta‐analysis were based on the “story type” of ToM task .45 Thep < 0.05 using an initial cluster‐forming threshold of p < 0.001 (uncorrected) was employed. To explore the relationship between whole‐brain activation and mentalizing network, the term “mentalizing” was searched for and the corresponding activation masks based on all 151 studies using the platform Neurosynth (neurosynth.org) was extracted, and the conjunction between whole‐brain activation and Neurosynth mentalizing masks was performed.In an exploratory whole‐brain analysis, a searchlight analysis to identify brain regions coding category‐specific information in each identity classification  separately across the whole brain was performed. The radius of each sphere was adjusted such that each searchlight contained ≈100 voxels. For the correction of multiple comparisons, a cluster‐level correction with a threshold of family‐wise error (FWE) correction with The activity similarity between the four chat categories  was explored by using an across‐subject correlation. The activation value for each chat category was averaged and the average activation value of each ROI was extracted. The similarity matrices within ROIs by calculating the correlation between all pairs of chat categories across subjects were calculated.n) was calculated using G*power. Statistical analysis of data was analyzed by AFNI software, CoSMoMVPA, MATLAB, and SPSS.The variance between chat categories was compared by using permutation tests. The significance of the classification accuracies by MVPA was assessed by using permutation tests. The average classification accuracies were present as the format of mean ± standard deviation. Sample size (The authors declare no conflict of interest.Z.W. and Y.C. contributed equally to this work. Z.D.W., Y.C., L.X.Z., and X.C.Z. conceived and designed the study. Z.D.W. and Y.C. obtained the findings. Y.C., Q.Z., and P.Y.Z. were responsible for the acquisition of data. Z.D.W. and Y.C. analyzed and interpreted the data. P.Y.Z., Q.Z., Y.P., J.C.R., S.P.W., J.L., R.C.K., X.X., B.S.Q. and D.R.Z. provided administrative, technical or material support. X.C.Z. supervised the study. Z.D.W. and Y.C. drafted the paper and all authors contributed to the critical revision of intellectual content.Supporting InformationClick here for additional data file.Supplemental Video 1Click here for additional data file.


Gestational diabetes mellitus (GDM) is a significant public health burden in Australia. Subsequent strain on healthcare systems is widespread and current models of care may not be adequate to provide optimal healthcare delivery. This study aimed to assess a current model of dietetic care with maternal and neonatal outcomes.Hospital medical record data from The Women’s Hospital, Melbourne, for women with GDM  (July 2105-May 2017) was retrospectively analysed. Adjusted linear and logistic regression were used to analyse associations between the number of dietitian consultations and maternal and neonatal health outcomes.Half of all women (50%) received two consultations with a dietitian. 19% of women received three or more consultations and of these women, almost twice as many were managed by medical nutrition therapy (MNT) and pharmacotherapy (66%) compared with MNT alone (34%). Higher odds of any maternal complication among women receiving 3 + consultations compared to those receiving zero , one , or two  consultations were observed. Lower odds of infant admission to the Neonatal Intensive Care Unit (NICU) were observed among women receiving one , two , or three + consultations , compared to no consultations.The optimal schedule of dietitian consultations for women with GDM in Australia remains largely unclear. Alternate delivery of education for women with GDM such as telehealth and utilisation of digital platforms may assist relieving pressures on the healthcare system and ensure optimal care for women during pregnancy. Gestational diabetes mellitus (GDM) affects 1 in 5 pregnancies globally  with preA diagnosis of GDM during pregnancy increases risk for multiple adverse maternal and neonatal health outcomes including pre-eclampsia, , 7 macroCurrent models of GDM care have been considered “unsustainable” in Australian healthcare settings . While nCurrently no Australian clinical practice guidelines exist for the dietetic intervention that women should receive when diagnosed with GDM. U.S. evidence-based guidelines  include This was a retrospective study of women (≥ 18 years of age) diagnosed with GDM (n = 1509) who gave birth between 1 and 2015 and 31 May 2017 at The Women’s Hospital, Melbourne. Ethics approval for this study was obtained by the Human Research Ethics Committee at The Women’s Hospital (17/08) and the Deakin University Human Research Ethics Committee (2017 − 190). Diagnosis of GDM was in accordance with the Australasian Diabetes in Pregnancy Society (ADIPS) (2014) criteria [Sociodemographic and health outcome data was collected from medical records . The Australian Bureau of Statistics’ (ABS) Standard Classification of Cultural and Ethnic Groups  was usedAt The Women’s Hospital, English-speaking women with GDM are scheduled for an initial group education session, led by a dietitian, to obtain dietary advice about carbohydrate types and portions to consume, daily food group requirements and meal planning strategies. Individual review appointments with a dietitian are scheduled two weeks after the initial group education session for review of the food diary and blood glucose record. The dietitian scheduled a ‘second review’ appointment for women reporting uncertainty or worry about their dietary management or indicated over-restriction of dietary intake. Further appointments were made by the consulting dietitian on an individual basis, using the same criteria. Culturally and linguistically diverse women received interpreter-assisted dietetic consultations for the initial education session and at least one review appointment, with additional review appointments scheduled as needed, using the aforementioned criteria. The number of dietetic consultations attended for each woman was determined through patient management system audits and categorised into levels ‘no dietetic consultations, ‘one dietetic consultation’ ‘two dietetic consultations’ or ‘three or more dietetic consultations. Women with GDM were also taught to self-monitor their capillary blood glucose levels (BGLs), which were reviewed weekly by the Credentialed Diabetes Educator, Obstetrician or Endocrinologist (depending on model of care). Pharmacotherapy (insulin or metformin) was initiated when indicated by persistent hyperglycaemia consistent with clinical practice guidelines at the Women’s Hospital. It should be noted that complete data for maternal glycaemic control were not available for this study and could not be included in the analysis.p < 0.05), stratified analyses were conducted to assess effects of consultations for MNT and MNT + pharmacotherapy separately. Confounders were identified and adjusted for in the analyses, consistent with the literature [Descriptive analyses were reported as mean(SD). Outliers were replaced with the next value that was not an outlier . For catterature –26. For terature , 26. DatOf 1509 adult women with GDM, 1,185 were included in the analyses. Exclusions included prior dietetic intervention for other obstetric issues (n = 83), antenatal care (including GDM care) received outside The Women’s Hospital, Melbourne (n = 59), multiple pregnancy (n = 47), self-reported polycystic ovarian syndrome (n = 38), inpatient admission for serious medical conditions (n = 36), incomplete data (n = 23), no multidisciplinary care received (n = 20), diagnosis outside the ADIPS diagnostic criteria (n = 8), number of dietetic consultations could not be determined (n = 1). Where women had two pregnancies during the study period (n = 9), data for the first pregnancy were included.Participant characteristics are shown in Table Associations between dietitian consultations and maternal complications are presented in Table Overall, 18% of women had one or more neonatal complication Table . Some evOverall, 19% of women in this study received at least three dietetic consultations during pregnancy and of these women, almost twice as many were managed by MNT + pharmacotherapy (66%) compared with MNT alone (34%). A high proportion of women in this study experienced maternal complications. Further, compared to women who did not see a dietitian during pregnancy, for those who did see a dietitian, lower odds of admission to NICU/SCN were observed. Whilst half of the women in our study saw a dietitian twice during pregnancy, less than one fifth of women in our study received GDM care according to the U.S evidence-based clinical practice guidelines of a minimum of three dietetic consultations. However, no evidence was shown that women who were seen in accordance with these recommendations had better maternal and neonatal health outcomes. This suggests that the current recommendations regarding schedule of consultations requires re-examination.The U.S MNT guidelines were developed for a contrasting health system and importantly, the schedule for the number of consultations was derived from expert consensus only . The guiThe mode of dietetic care delivery for MNT is another area that should be re-evaluated. The U.S MNT practice guidelines recommend that consultations be individual rather than group-based . Yet curThe need to ‘modify’ and ‘modernise’ approaches to GDM care for women has emerged as a critical priority in Australian healthcare . Whilst There are both strengths and limitations of this study. Firstly, we included a large and culturally diverse sample of women with GDM who gave birth at a large metropolitan maternity hospital in Melbourne. We adjusted for multiple, important confounders in our analyses which strengthened the observed relationship between number of dietetic consultations and maternal and neonatal outcomes. However, we cannot infer causality from our results due to the retrospective study design. We were not able to obtain glycaemic management data which is an important limitation as this and would likely have influenced both maternal and neonatal outcomes. Further, as this was a retrospective study we were unable to assess dietary intake change following group education or individual dietetic management. Dietary change is a key outcome and should be considered in future research alongside assessment of maternal and neonatal health outcomes in women with GDM.The optimum number of consultations to achieve best maternal and neonatal health outcomes remains uncertain. An individualised approach to GDM management is necessary to achieve optimal pregnancy outcomes. Current MNT guidelines lack applicability to differing health resource settings such as Australia. Future research into alternate methods for the delivery of MNT are needed to ensure health services have the capacity to deliver evidence-based care to women with GDM.


Leukemic retinopathy is a severe complication of severe leukocytosis that results from untreated chronic myelogenous leukemia (CML). Immediate cytoreduction via leukapheresis may reverse ocular manifestations and prevent permanent vision damage. We present a case of a patient with acute unilateral vision loss found to have leukemic retinopathy in the setting of untreated CML with improvement of visual symptoms after leukapheresis and initiation of hydroxyurea. Colour ophthalmologic photo of the left eye showing numerous Roth spots in macula and periphery with intraretinal hemorrhages, cotton wool spots, and vascular sheathing concerning for central retinal vein occlusion. Retinal hemorrhages can also be seen during the development of this disease and are usually present in the posterior pole and accompanied by a white centre with leukemic cells, platelet‐fibrin aggregates or septic embolic. Cotton wool spots can also be seen. Hyperviscosity can also present as a bilateral central retinal vein occlusion.The mainstay of treatment of leukemic retinopathy is chemotherapy targeted at the underlying disorder. However, leukapheresis is a treatment modality that has been shown in some case reports to have successfully reversed vision loss and ophthalmologic damage. Leukapheresis is emerging as an efficacious adjunct or initial treatment option for patients with severe retinopathy.We present a case of severe leukemic retinopathy leading to acute unilateral vision loss that was successfully treated with leukapheresis along with hydroxyurea.2A man in his early 40s with no past medical history presented to the emergency department with 3 days of left eye pain and associated worsening blurry vision. He was initially evaluated at a local optometry clinic and found to have retinal hemorrhages with decreased visual acuity and a central retinal vein occlusion Figure  and refeInitial laboratory values were significant for leukocytosis of 477 K/cumm with 10% blasts, 4% basophils, 4% eosinophils, and platelets of 276 K/cumm. Computed tomography imaging was notable for hepatomegaly and a markedly enlarged spleen with mass effect on the organs of the left hemi‐abdomen. Bone marrow biopsy was performed with results indicating marked leukocytosis and circulating blasts of 7%. BCR‐ABL genetic test was obtained and was positive, confirming the diagnosis of CML.A femoral central venous catheter was placed and the patient was initiated on leukapheresis on day one of admission. He was given 3 g of hydroxyurea in the emergency department and then started on hydroxyurea 2 g twice a day. White blood count initially increased to 533 K/cumm and 487 K/cumm after leukapheresis. Over the course of his hospitalisation, his visual symptoms improved after leukapheresis with nearly total improvement of his left visual deficits within 2 days. His leukocytosis began to resolve in the days following leukapheresis, initially decreasing to 340 K/cumm the day after the procedure and decreased to 245 K/cumm on hospital day four.The patient was discharged on hospital day 4 with 2 grams of hydroxyurea three times a day for 2 weeks with planned hematology follow‐up and initiation of a tyrosine kinase inhibitor.Two weeks after, ophthalmologic photos were obtained demonstrating improvement of the central retinal vein occlusion, intraretinal hemorrhages, and cotton wool spots Figure . At foll3Ocular complications may manifest as a symptom of severe, untreated leukemia. Although the pathophysiology behind ocular manifestations of CML is not well understood, it is most likely multifactorial. These mechanisms likely include infiltration by neoplastic cells leading to reduced blood flow, vascular stagnation, ischemia, and anemia.Although the mainstay of treatment for leukemic retinopathy remains induction chemotherapy at the underlying disorder, leukapheresis has become more common as an adjunctive or initial treatment. Prompt, effective reduction of the high white cell count can cause rapid improvement of visual symptoms. Leukapheresis aids in prompt reversal of microvascular sludging and should be considered for rapid cytoreduction during the initial stages, since drugs such as hydroxyurea or BCR‐ABL tyrosine kinase inhibitors take a longer time to demonstrate their cytoreductive effects.However, leukapheresis remains controversial as it has variable results in overall mortality benefits and has not been well‐studied in different types of leukemia. Larger prospective studies have not shown consistent benefits or decreases in early morality rates and have only been studied in acute myeloid leukemia (AML) cases.Although leukapheresis in current studies have not been proven to have overall mortality benefits, our case shows that there may be a role for this procedure in reducing permanent vascular damage. Our patient successfully had reversal of his acute vision loss and was able to initiate chemotherapy shortly after his initial presentation. Further studies are needed to demonstrate the benefits of symptom relief of severe leukocytosis in conjunction with chemotherapy and hydroxyurea.Sally Leong: Data curation; investigation; writing – original draft; writing – review and editing. Tiffanie Do: Data curation; writing – review and editing. Michael Shodiya: Conceptualization; writing – review and editing. Jennifer Lee: Conceptualization; supervision; writing – review and editing.There was no funding obtained for this article. This article was written under the employment of the above affiliations.SL, TD, MS, JL have no conflicts of interest to declare.Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.


The current prostate cancer (PCa) screening standard of care (SOC) leads to unnecessary biopsies and overtreatment because decisions are guided by prostate‐specific antigen (PSA) levels, which have low specificity in the gray zone (3–10 ng/mL). New risk assessment tools (RATs) aim to improve biopsy decision‐making. We constructed a modeling framework to assess new RATs in men with gray zone PSA from the British Columbia healthcare system's perspective.We evaluated the cost‐effectiveness of a new RAT used in biopsy‐naïve men aged 50+ with a PSA of 3–10 ng/mL using a time‐dependent state‐transition model. The model was informed by engaging patient partners and using linked administrative health data, supplemented with published literature. The incremental cost‐effectiveness ratio and the probability of the RAT being cost‐effective were calculated. Probabilistic analysis was used to assess parameter uncertainty.In the base case, a RAT based on an existing biomarker's characteristics was a dominant strategy associated with a cost savings of $44 and a quality‐adjusted life years (QALY) gain of 0.00253 over 18 years of follow‐up. At a cost‐effectiveness threshold of $50,000/QALY, the probability that using a RAT is cost‐effective relative to the SOC was 73%. Outcomes were sensitive to RAT costs and accuracy, especially the detection rate of high‐grade PCa. Results were also impacted by PCa prevalence and assumptions about undetected PCa survival.Our findings showed that a more accurate RAT to guide biopsy can be cost‐effective. Our proposed general model can be used to analyze the cost‐effectiveness of any novel RAT. These tools include PSA kinetics, PSA density, percent‐free PSA, urine or liquid biomarker panels, and prostate risk calculators.22.1We developed a time‐dependent cohort state‐transition model, a dynamic model in which a hypothetical cohort of individuals transitions between different health states and the transition probabilities change over time. This model was used to evaluate the cost and effectiveness of a RAT strategy following the PSA compared with SOC  to guide the initial biopsy decision. The analysis was from the perspective of the publicly funded healthcare payer in British Columbia (BC), Canada. The target population consisted of men aged ≥50 years,Figure The cycle length was 1 year. The cohort of patients in both strategies was simulated over a time horizon of 18 years similar to cost‐effectiveness studies2.2We used administrative health data to inform most of the model parameters,2.2.1Using linked administrative health data from BC Cancer and Population Data BC, we constructed a cohort of men aged ≥50 years with a diagnosis of PCa between 2010 and 2017 (Cohort 1 “cases”) and followed them from the date of diagnosis until death, the last date of observation, or December 31, 2019, whichever came first. We also created a cohort of PCa patients who were diagnosed with PCa after 1997 and died from PCa after 2010 (Cohort 2 “cases”) to facilitate the estimation of healthcare costs for the year before death. Controls who were No‐PCa individuals from the BC general population were matched to the cases in each cohort; details on matching are described in the Method 2.2.2We estimated the probabilities of different follow‐up pathways based on Cohort 1 patients who had a PSA level in the gray zone (by grade at diagnosis and by treatment option within the first year of diagnosis). Using these data, we also calculated PCa‐specific mortality rates stratified by the grade of PCa in different health states to inform the transition probabilities. In the base case, men with undetected high‐grade and low‐grade PCa were assumed to have the same PCa‐specific mortality as untreated patients (WW/AS) in Cohort 1.In scenario analyses, we tested the impact of this assumption and calculated the yearly probability of death of undetected high‐grade cases; we applied the hazard ratio of PCa‐specific mortality in treated patients versus patients under WW from the Bill‐Axelson et al.2.2.3Many biomarkers  in Cohort 1. The cost of undetected cases was calculated based on this ratio and the respective costs of untreated patients in the advanced and early stages Table .We only considered the incremental cost of the intervention, that is, the cost of the RAT itself, because the tool is an add‐on to the current SOC. The cost of SOC itself cancels out when comparing strategies. The cost of biopsy was estimated using the Discharge Abstract Database from Population Data BC,2.2.5The disutility assigned to different diagnosis and treatment health states and their duration were primarily obtained from Heijnsdijk et al.2.3Both costs and quality‐adjusted life years (QALYs) were discounted at 1.5% per year as recommended by the guidelines of the Canadian Agency for Drugs and Technologies in Health.2.3.1We conducted a series of scenario analyses to assess how changes in input parameters and model assumptions could affect the outcomes. First, we evaluated the impact of PCa prevalence, cost of RAT, and RAT accuracy. While MRI is not yet the SOC for PCa in BC,33.1Results of the base case analysis are presented in Table 3.2Table 4This study provides a general modeling framework to evaluate the impact on outcome and resource use of using any new RAT to inform PCa diagnosis decisions. Our cost‐effectiveness analysis demonstrated that incorporating an accurate tool in the initial diagnosis of PCa in men with PSA levels in the gray zone can be a cost‐effective (or dominant) strategy by avoiding unnecessary biopsies and overtreatment. Our extensive set of scenario analyses further revealed that the cost‐effectiveness results were sensitive to the tool's accuracy, especially the detection rate for high‐grade PCa. The results also showed that, for a RAT to be cost‐effective, its sensitivity must be relatively high (>0.955); however, this sensitivity could change with the different proportions of high‐grade PCa in the sample. The cost of RAT and PCa prevalence can also impact whether RAT is cost‐effective compared to PSA alone. The results showed that RAT can be a dominant strategy at costs below $314, given other RAT characteristics and assumptions made in the base case. We also found that the cost‐effectiveness results were impacted by the different assumptions on cost and survival rate of the undetected cases resulting from using a RAT to guide biopsy.The results of scenario analyses for evaluating the impact of changes in model inputs align with previous studies conducted to assess the value of specific biomarkers or other diagnostic methods.This study has some limitations. First, the cost‐effectiveness analysis was performed from the BC healthcare payer's perspective, and BC data were used to inform the model, which might limit the generalizability of results to other provinces or countries. Nevertheless, our proposed modeling framework can be easily modified to analyze the cost and effectiveness of using a new RAT to direct PCa diagnosis in another setting. Second, the SOC in the model illustrates a strategy of using PSA alone to guide biopsy and thus, may not fully represent current practice for PCa diagnosis . However, since we estimated our cost and mortality model parameters using the population‐based administrative data, the costs of MRI or sequential PSA testing, if any, and their impact have been implicitly considered. Furthermore, any strategy different from the SOC could be represented as a RAT in our model and scenario analyses to evaluate its cost‐effectiveness. Third, although we attempted to minimize the confounding effect using the matching method when estimating incremental costs and mortality attributable to PC, these estimates may still be confounded. For example, we matched on the number of comorbidities rather than the exact conditions. Lastly, in our study, we employed a time‐dependent cohort state‐transition model. While the existing microsimulations model, such as the Fred Hutchinson Cancer Research Center (FHCRC) model,Importantly, a key strength of this study was taking a more conservative approach by considering the impact of undetected PCa on patient survival, quality of life and costs. The decrease in utility or associated costs of PCa cases missing due to false negative RAT results was not taken into account in some previous studies.Another key strength of this work is our collaboration with patient partners and clinicians to define the diagnostic pathway as the basis for our economic model. Both stakeholder groups emphasized the need for a better RAT than PSA alone to guide biopsy decisions, especially for the PSA gray zone, and provided unique insights on the diversity and complexity of diagnosis and treatment pathways. Another important strength is our use of real‐world, whole‐population administrative health data from multiple data sources to inform the model. This provided a more accurate reflection of the current practice and diversity of treatment pathways in the cost‐effectiveness analysis. Lastly, we characterized uncertainty in the model input parameters as a distribution and conducted a probabilistic analysis for the base case and all 36 scenarios through Monte Carlo simulation.5This study found that a new or emerging more accurate RAT to guide clinical decisions about biopsy in men at risk of PCa can be a dominant strategy compared to the SOC. However, the cost‐effectiveness decisions about a RAT are sensitive to its cost and accuracy, especially the detection rate for high‐grade cancers. This study also provides a general economic evaluation framework to analyze the cost‐effectiveness of any novel marker to improve the diagnosis process of PCa.Tima Mohammadi: Conceptualization ; data curation (supporting); formal analysis (lead); investigation (lead); methodology (lead); software (lead); validation (lead); visualization (lead); writing – original draft (lead); writing – review and editing (lead). Daphne P. Guh: Conceptualization ; data curation (supporting); formal analysis (lead); investigation (lead); methodology (lead); software (lead); validation ; writing – review and editing . Alexander CT Tam: Data curation (supporting); investigation (supporting); project administration ; writing – review and editing . Reka E. Pataky: Data curation (supporting); investigation ; methodology ; validation ; writing – review and editing . Peter Black: Investigation ; resources (supporting); validation (supporting); writing – review and editing . Alan So: Investigation ; resources (supporting); validation (supporting); writing – review and editing . Larry Lynd: Conceptualization (lead); funding acquisition (lead); methodology ; project administration (supporting); resources ; writing – review and editing . Wei Zhang: Conceptualization (lead); data curation (lead); funding acquisition (lead); investigation ; methodology ; project administration ; resources ; supervision ; validation ; writing – original draft (supporting); writing – review and editing . Annalijn I. Conklin: Conceptualization (lead); data curation (lead); funding acquisition (lead); investigation ; methodology ; project administration ; resources ; supervision ; writing – review and editing .This work was supported by a GlycoNet Collaborative Team Grant from the Canadian Glycomics Network, project titled ‘The early study: ECONOMIC evaluation of a novel prostate cancer glycan‐based diagnostic tool (CR‐01)’, with matched funding from the Michael Smith Health Research BC, the University of British Columbia Faculty of Pharmaceutical Sciences, and the Centre for Health Evaluation and Outcome Sciences. WZ and AIC are independently supported by the Michael Smith Health Research BC Scholar award. RP is independently supported by the Canadian centre for Applied Research in Cancer Control (ARCC), which is funded by the Canadian Cancer Society. ACTT was previously independently supported by the Canadian Institutes of Health Research Canada Graduate Scholarship‐Master's at the time this research was conducted. The funder did not play a role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication.The authors declare no conflict of interest.The study was approved by the behavioral research ethics board of the University of British Columbia (H20‐01258).Appendix S1.Click here for additional data file.


Anomalous insertion of chordae is a rare disease that could be associated with hypertrophic obstructive cardiomyopathy (HOCM), but clinical and echocardiographic diagnoses tend to be delayed. Alcohol septal ablation has emerged as an alternative to surgical myomectomy in HOCM. When a patient showed an anomalous insertion of chordae, physicians generally opt for surgery and not alcohol septal ablation. In this report, we present the case of a lady, with symptomatic HOCM associated with a chord inserted on the left ventricular outflow tract. We succeeded to relieve obstruction by alcohol septal ablation without the need for surgery. Abnormal insertion of mitral chordae associated with hypertrophic obstructive cardiomyopathy with significant turbulence across the LV outflow tract. Her medical history was unremarkable.The cardiac auscultation showed an ejection systolic murmur (grade 4/6) in the aortic area. General examination and other systems examination were unremarkable. A 12‐lead electrocardiogram showed sinus rhythm at 90 beats/min with left ventricle hypertrophy.A transthoracic echocardiogram (TTE) demonstrated an asymmetric interventricular septal hypertrophy of LV walls  with a normal ejection fraction but a severe subvalvular aortic stenosis with significant turbulence across the LV outflow tract (LVOT) in color Doppler and a late‐peaking “dagger‐shaped” systolic jet assessed by continuous‐wave Doppler.The peak velocity exceeds 7 m/s with a maximal gradient of 210 mm Hg.A transesophageal echocardiogram showed also a moderate systolic anterior motion with septal contact lasting less than a third of the systolic period and two chordae attached to the interventricular septum and mitro‐aortic trigona.The aortic valve was tricuspid with a normal orifice area.MRI was also performed to evaluate the mitral subvalvular apparatus. It showed the two chordae crossing the left ventricular outflow tract, and the analysis of dynamic sequences showed that the obstruction is the consequence of the hypertrophy of the basal septal segment Figure .The evaluation of sudden cardiac death (SCD) using the HCM‐SCD score showed a score of 3%, and there was no indication of implanting a defibrillator.The patient had been treated with beta‐blockers and calcium channel blockers for 3 months but remained symptomatic, and the LVOT obstruction did not improve.The lady refused surgery and the heart team after discussion with the patient decided to try an alcohol ablation. The lady signed consent and accepted all the risks of the procedure.Coronary angiography was performed via a transradial approach. The left main coronary artery was cannulated with an EBU 6 Fr guiding catheter, a 0.014 guidewire was placed into the proximal septal branch, a (2.5 × 10 mm) over‐the‐wire (OTW) balloon was advanced into the guidewire placing it in the ostium of the septal branch, and it was inflated up to 12 atm.During probatory inflation of the balloon, the gradient resolved completely, and we were convinced that the obstruction is due to the septal hypertrophy, not to abnormal chordae. Desiccated alcohol of 96% was used.Alcohol septal ablation (ASA) was performed with a single slow injection of 2 mL of alcohol over 4 min. We did not note any further complications. We obtained a slow flow in the first septal and the outflow tract gradient disappeared on invasive pressure measurements  after the procedure was at 1450 U/L.TTE and invasive control of pressure showed also a decrease in the LVOT gradient at 20 mm Hg Figure . Two‐dim3Congenital malformations of the LV papillary muscles, including the anomalous chordal insertion, is a rare anomaly leading to LVOT obstruction with an incidence of 1 per 26,000 echocardiograms in adults.Standard echocardiographic windows and modified windows should be used to identify the chordal abnormalities during the echocardiographic examination of patients with HCM.Symptomatic HOCM patients are usually treated first with β‐blockers or calcium channel inhibitors. In case of failure of medical treatment, physicians opted for surgery, no cases of ASA have been reported to our knowledge.Our case demonstrated that the main mechanism of obstruction in some patients is the hypertrophy of the basal part of the septum. In our patient, we decided to try to occlude the first septal with a balloon and to check whether the gradient will decrease during the procedure.This test could be a solution to assess the immediate result of alcohol ablation. After this test, the operator could decide whether he continues the ASA procedure or opts for surgery.In our case, the gradient had remarkably disappeared during the occlusion test and the ASA was performed with a good result and without any complications.4We showed that ASA is feasible in patients with anomalous chordae associated with HOCM. The analysis of imaging (MRI) and Doppler color is very important to decide. Moreover, the occlusion test with OTW could be very helpful if we obtained an immediate decrease in the outflow gradient.Rania Hammami: Supervision; writing – original draft. Amine Kammoun: Writing – original draft. Majed Hassine: Resources; validation; writing – review and editing. Tarek Ellouze: Writing – review and editing. Rania Gargouri: Writing – review and editing. Leila Abid: Writing – review and editing.None.The authors declare no conflict of interest.Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.


Peripapillary hyperreflective ovoid mass‐like structures (PHOMS) are a laterally bulging herniation of distended axons into the peripapillary region above the level of Bruch's membrane opening. Increased use of enhanced depth imaging‐optical coherence tomography (EDI‐OCT) in our evaluation of the optic nerve head (ONH) and greater recognition of the vast range of optic nerve pathologies with which PHOMS is associated provides convincing evidence that PHOMS is not just buried optic disc drusen (ODD) as previously described. The frequent coexistence of PHOMS with ODD, papilloedema, anterior ischaemic optic neuropathy, tilted optic disc syndrome, inflammatory demyelinating disorders and other diseases associated with axoplasmic stasis provides insight into its underlying pathophysiology. The present review will discuss the role of key imaging modalities in the differential diagnosis of PHOMS, explore the current literature on the relationship between PHOMS and common neuro‐ophthalmic conditions, and highlight the gaps in our knowledge, with respect to disease classification and prognosis, to pave the way for future directions of research. Furthermore, we highlight current gaps in our knowledge regarding the relevance of PHOMS with respect to disease classification, prognosis and as a potential clinical trials endpoint measure.2The earliest OCT report of a PHOMS‐like subretinal hyperreflective lesion was described in 45 patients with presumed ‘buried ODD’.2.1en face image, reconstructed from OCT volume scans, can be used to determine the circumferential extent of PHOMS around the disc margin  which are displaced upwards to give the impression of a blurred and elevated disc margin. PHOMS does not invade or infiltrate peripapillary retinal tissue but rather acts like a space occupying lesion producing a ‘ski slope’‐like deflection of the inner retinal surface, slanting down and away from the disc margin.PHOMS are defined by their location, internal optical features, shape and effect on surrounding tissues.The ODDS Consortium recommended the use of a dedicated optic disc OCT scanning protocol in addition to the commonly used peripapillary RNFL circle scan in the assessment of ODD and visualisation of PHOMS. The OCT and EDI‐OCT protocols for disc imaging are shown in Figure OCTA provides visualisation of the internal vascularity of PHOMS, peripapillary vascular network and quantification of the retinal microvasculature. Ahn et al. found vessel densities measured in the papillary and peripapillary region were significantly lower in children harbouring large PHOMS (height ≥ 500 μm) as compared to controls.2.2Near‐infrared reflectance (NIR) imaging has demonstrated a hyporeflective ring nasal to the disc margin, correlating with the exact location of the PHOMS edge.Alexander Fraser et al. reported PHOMS could only be detected on OCT and not with US or computed tomography (CT).3n = 12 eyes), optic neuritis (n = 11 eyes) and ODD (n = 9 eyes).PHOMS has been shown to accompany a wide spectrum of ocular and neurologic diseases that share an underlying pathophysiological process of axonal compression and stasis. However, the relative contribution of each of these causes depends on the patient's age. In a case series of 45 eyes from 45 children with PHOMS under the age of 18 years, ODD was seen in 16 eyes (36%).3.1ODD are discrete lesions composed of acellular, extracellular concretions that are usually calcified and located in the unmyelinated RNFL anterior to the lamina cribrosa.In a case series of children with ODD, Teixeira et al. found 89% had concomitant PHOMS in the same eye located predominantly in the nasal, superonasal and inferonasal sectors similar to the distribution of ODD.3.2Bilateral optic disc swelling due to raised intracranial pressure (ICP) is known as papilloedema. Raised cerebrospinal fluid (CSF) pressure around the optic nerve alters the normal pressure gradient between the eye (intraocular pressure) and the retrolaminar tissue (ICP). The reversal of the trans‐lamina cribrosa pressure difference (TLCPD) results in orthograde axoplasmic flow stasis, disc swelling and vascular congestion. The most common cause of papilloedema is idiopathic intracranial hypertension (IIH), defined by the combination of raised intracranial pressure, without hydrocephalus or mass lesion, with a normal composition of the CSF and an absence of an underlying cause found.Wibroe described the prevalence of PHOMS in a cohort of patients with IIH‐related papilloedema.3.3In those over 50 years, AION is the most common acute optic nerve disease with 90% being nonarteritic (NA) in nature.Hamann et al. reported ODD present in 51% of NA‐AION eyes in patients 50 years or younger. Of the unaffected fellow eyes 43% had ODD. Just over half of these young NA‐AION patients had ODD in one (29%) or both (71%) eyes. Among the 74 eyes with NA‐AION, 23 (31%) had PHOMS. The prevalence was higher if ODD was also present (54% with vs. 28% without ODD). In another case series, 5 of 9 (56%) patients with NA‐AION were found to have PHOMS but most of these (6 of 9) had co‐existing ODD.3.4Torsion and tilting of the ONH were previously considered congenital anomalies but are now also recognised in progressive myopia. In an ovalised ONH, a torted disc is defined by >15° of rotation of longest axis from the vertical meridianPichi et al. first described herniation of the nerve fibres above the protrusion of Bruch's membrane and the choroid from the nasal side of the disc in 15 of 38 (39%) eyes or 14 of 20 (70%) patients with tilted discs.3.5Multiple sclerosis (MS) is a CNS inflammatory demyelinating disorder characterised by sensory and motor dysfunction and loss resulting from immune‐mediated demyelination and subsequent axonal damage. The prevalence of MS in Hobart (latitude of 42.5° S) was 147 per 100 000 in 2019 and the age‐standardised incidence was 6.1 per 100 000 person‐years (during 2009–2019).Petzold et al. explored the association of PHOMS in MS cases with and without a history of optic neuritis.3.6Given PHOMS is a sign of axoplasmic stasis, it is not surprising that other retinal disorders and orbital diseases which cause compartment syndrome at the ONH or optic nerve compression may predispose to its formation. Dai et al. reported 3 of 25 patients with CRVO and 3 of 14 patients with branch‐RVO (BRVO) had accompanying PHOMS.4Redefining peripapillary hyperreflective ‘buried ODD’ as PHOMS has enhanced our understanding of a common pathway in ONH compartment syndrome and axoplasmic stasis due to a wide range of CNS, optic nerve and retinal diseases. Multimodal imaging including EDI‐OCT, NIR, FAF and US are essential for both the characterisation of PHOMS and determining the underlying disease process precipitating the herniation of nerve fibres. Incorporating a high density optic disc raster and radial scans as set out by the ODDS consortium into our routine ONH assessment will enhance the detection rate and allow for a longitudinal analysis of PHOMS evolution and regression. The inclusion of visual field or microperimetric analysis in diseases with a high frequency of PHOMS may help to determine the relevance of nerve fibre herniation as a potential risk factor for permanent axonal loss. PHOMS as biomarker of optic nerve compartment syndrome should be considered as an exploratory endpoint measure in future clinical trials examining the treatment of papilloedema, AION, myopia progression, CNS demyelination and other diseases that lead to optic disc oedema. Future histological studies of eyes that have clinical evidence of PHOMS is essential for confirming the hypothesis that this toroidal hyperreflective structure originates from herniated optic nerve fibres as a response to ONH compartment syndrome.This study was supported by the National Health & Medical Research Council of Australia (project and fellowship grant number: GNT1116360 (FKC), GNT1188694 (FKC), GNT1054712 (FKC) and MRF1142962 (FKC)), the McCusker Foundation (FKC), the Miocevich Retina Fellowship (RCHJ) and Channel 7 Telethon Trust (FKC).The authors declare no conflict of interest.Patients have given consent for these images to be used in a prospective study. Ethics approval was obtained from the Human Ethics Office of Research Enterprise, the University of Western Australia  and Sir Charles Gairdner Hospital Human Research Ethics Committee (2001‐053).


Cuculus canorus), and their hosts are one of the best‐studied examples of the coevolutionary arms race. Different stages of this arms race can be seen in different races of common cuckoos and their hosts across their range. However, little is known whether selected populations of two closely related but geographically distant species with probably different coevolutionary histories with the common cuckoo are also at different stages of the arms race. In this study, we tested this prediction experimentally using the same non‐mimetic model eggs and three‐dimensional (3D) printed models of the gray adult common cuckoo (Cuculus canorus). We examined egg recognition and egg rejection and aggression against the common cuckoo in the great reed warbler  and Oriental reed warbler , in Slovakia of Europe and northeast China of Asia. The results showed that the great reed warbler exhibited stronger responses to experimental model eggs and 3D models of the common cuckoo than the Oriental reed warbler. We conclude that both the great reed warbler and Oriental reed warbler have well‐developed antiparasitic behaviors against common cuckoos in the studied populations, but with different levels of defense intensity, which may be due to local differences in parasitic pressure and the risk of parasitism. This provides an opportunity to study coevolutionary processes between the brood parasite and its hosts together in both species at large geographical scales.Interactions between avian brood parasites, such as common cuckoos  and Oriental reed warbler , in Europe and China. The great reed warbler exhibited stronger responses to experimental model eggs and 3D models of the common cuckoo than the Oriental reed warbler. Both the great reed warbler and Oriental reed warbler have well‐developed antiparasitic behaviors against cuckoos but with different levels of defense intensity, which may be due to local differences in parasitic pressure and the risk of parasitism.We experimentally use the same eggs and models to compare egg recognition and egg rejection and aggression against cuckoos in its two hosts, the great reed warbler ( This is because of high fitness costs imposed by brood parasitism on hosts selected for a variety of highly sophisticated adaptations and counter‐adaptations between interacting species, resembling an arms race Davies, . The mosCuculus canorus) and its two hosts, the great reed warbler  and the Oriental reed warbler  in Hungary and Japan. Both species showed moderately evolved antiparasitic defenses at the study sites. Nevertheless, despite similar egg rejection rates in the two host species, cuckoo eggs found in Hungary showed better mimicry to host eggs than cuckoo eggs found in Japan, which suggests that coevolutionary mechanisms may have different speeds and the common cuckoo and its hosts may be at different stages in arms race in the two distant areas. However, although egg recognition and egg rejection are important indicators of host adaptation to brood parasitism  and northeast China, which has not been studied to date. The great reed warbler is one of the largest species in the family Acrocephalidae breeding throughout mainland Europe and the west Palearctic and wintering in Sub‐Saharan Africa. It is a facultatively polygynous species, with rates of social polygyny ranging from 8% to 56%  as stimuli to standardize experimental conditions in both study areas. Artificial eggs and dummies of brood parasites, including 3D models, are used commonly and successfully also in other host egg rejection and host aggression studies  printed models of adult common cuckoos and Oriental turtle doves , and two sites in northeast China, Baiyangdian Lake, Hebei  and Sifangtuozi Farm, Jilin . The two sites in China are about 1300 km apart.Phragmites australis) that border the ponds. In the study year, the great reed warbler population comprised 40–50 breeding pairs and the parasitism rate by the common cuckoo reached 35.7% (N = 42).The Luba study site is located in a warm, temperate climate zone, with an annual average air temperature of 10.4°C (min–max: −35.0–40.3°C) and annual average precipitation of 556 mm. The great reed warbler breeds here in narrow, approximately 5–10 m wide, strips of the common reed (N = 28/141). The birds breed here in reed wetlands.The study site Hebei represents the largest freshwater shallow lake in the north China Plain, located in a warm, temperate, and semi‐arid continental monsoon climate zone. The annual average air temperature here is 12.2°C, with an extreme maximum temperature of 40.7°C and an extreme minimum temperature of −26.7°C. The annual average precipitation and evaporation are 529.7 and 993.0 mm, respectively . The habitats included reed wetlands, open waterbodies, and cultivated lands, and most Oriental reed warblers nested in reed wetlands.The site Jilin is located in a semi‐arid temperate continental monsoon climate zone, with an annual average temperature of 4.4°C and average annual precipitation of 384–521 mm  and from June to August (Hebei and Jilin). Most nests were found during building or egg‐laying. Once a nest was found, we checked it at 2–3 days intervals to determine the day of clutch completion, the final clutch size and to detect the presence of a parasitic egg. We determined the current social mating status of each female and her mate based on their captures at the nests during the nest‐building or egg‐laying stages (Luba), or we tested only the first nest in each male's territory that could be regarded as the nest of a currently monogamous female (Hebei and Jilin). Note that monogamous females receive much more male nest defense assistance than females of polygynous males, which might influence their nest defense behavior , similar to the size of local cuckoo eggs . The model size of the two species is similar to real birds about 28 and 30 cm, respectively. And the tail of the cuckoo model is upturned to simulate the resting position in nature. We applied sequential randomized presentation of models at host nests. The time lag between the two presentations was at least 90 min to prevent habituation or carry‐over aggression of the tested birds. To minimize the risk of nest desertion caused by disturbing a female during egg laying, we conducted all experiments 1–2 days after clutch completion. The models were placed 0.5 m from the focal nest, at the height of the nest rim, with the head facing the nest. Observations were made by the same observer from a shelter placed 4–5 m away from the nest (Luba), and responses of hosts were video‐recorded with a micro camera  above the nest  appeared near the nest and spotted the model, and lasted for 5 min. If no parent was observed near the nest for 15 min since the model was exposed, the experiment was stopped and excluded from the analyses. Host behavior was quantified on the following scale: (1) no response, the bird silently watched the model from a safe place; (2) alert, the bird approached the nest giving short alert calls; (3) mobbing, the bird jumped closely around the model or flew over it, giving alarm and distress calls; (4) attack, the bird physically attacked the model, persistently uttering distress calls. As both the great reed warbler and Oriental reed warbler are sexually monomorphic and the color rings on the legs of birds are only difficult to identify due to their fast movements in dense reeds, we did not distinguish different individuals by sex during experiments. We used the maximum reaction of parents in the analysis. Both above‐mentioned procedures for quantifying egg‐rejection behavior and nest defense behavior were successfully used in the two study species also in our previous studies  with logit‐link function were used to predict the response  toward the dummy (cuckoo or dove model) in different study areas . And we used two‐tailed likelihood ratio tests to obtain p < .05, and data are presented in the form of mean ± standard deviation (Mean ± SD).Fisher's exact test or Chi‐square test was used for comparison between different probabilities. All tests were two‐tailed, with a significance level of 33.1p = .026), with egg rejection rate in Luba (92.6%) being higher than in Hebei and Jilin , data from the two sites were merged for further comparison with Luba. The result then indicated that the great reed warbler shows a much stronger egg rejection than the Oriental reed warbler .Out of 56 experimentally parasitized great reed warbler and Oriental reed warbler nests hosts rejected the blue model egg in 44 (78.6%) nests, most frequently by ejection (35 cases). There were significant differences in egg rejections among the three study sites  and type of model  were the two factors that could predict the response toward the model in different study areas  was apparent in 45 of 58 (77.6%) tested nests, direct body attacks were observed in 33 of 58 (56.9%) nests. CLMMs showed that study site , then data of the two sites were merged for further comparison with Luba, and the results indicated that the interaction between species and type of model significantly affected the responses of birds , whereas there was no significant difference in response intensity between cuckoo and turtle dove models for Oriental reed warbler . In addition, the response intensity of great reed warbler to cuckoo model was significantly higher than that of Oriental reed warbler , while the responses of the two species to the dove were not different .There was no difference between Hebei and Jilin in nest defense scores to two types of models  eggs in our egg rejection experiments, which could have skewed the results. Given that the degree of egg mimicry is an important factor in host recognition ; formal analysis ; investigation ; writing – original draft (lead); writing – review and editing . Laikun Ma: Formal analysis ; investigation . Hanlin Yan: Investigation . Longwu Wang: Investigation . Wei Liang: Conceptualization ; funding acquisition (lead); resources ; writing – review and editing .This work was supported by the National Natural Science Foundation of China . LW was funded by the Guizhou Natural Science Foundation (No. ZK [2022]‐316), and WL was supported by the specific research fund of The Innovation Platform for Academicians of Hainan Province.The authors declare that they have no competing interests.The study was conducted in compliance with the law of Slovakia and China. The licenses and permissions to handle and ring the birds in Slovakia were issued by the Ministry of Environment of the Slovak Republic (number 3320/2019–6.3). Experimental procedures in China were in accordance with the Animal Research Ethics Committee of Hainan Provincial Education Centre for Ecology and Environment, Hainan Normal University (no. HNECEE‐2012‐003) and Guizhou Normal University (No. GZNUECEE‐2021‐001).


Non‐suicidal self‐injury (NSSI) is common in adolescents receiving psychiatric treatment and is a significant risk factor for suicidal behavior. There are few randomised clinical trials assessing interventions for NSSI in youth, and knowledge about internet‐delivered interventions is limited.We assessed the feasibility of Internet based Emotion Regulation Individual Therapy for Adolescents (ERITA) in psychiatric outpatients aged 13–17 years who engaged in NSSI.A randomised clinical feasibility trial with a parallel group design. Non‐suicidal self‐injury engaging patients were recruited from Child and Adolescent Mental Health Outpatient Services in the Capital Region of Denmark from May to October 2020. ERITA was provided as add‐on to treatment as usual (TAU). ERITA is a therapist‐guided, internet‐based program of emotion regulation and skills training involving a parent. The control intervention was TAU. Feasibility outcomes were the proportion who completed follow‐up interviews at end of intervention; proportion of eligible patients who participated in the trial; proportion of participants completing ERITA. We further investigated relevant exploratory outcomes, including adverse risk‐related events.We included 30 adolescent participants, 15 in each group . 90%  of the participants completed post‐treatment interviews; 54%  of the eligible participants were included and randomised; and 87%  of the participants completed at least six out of 11 ERITA modules. We identified no difference for the primary exploratory clinical outcome of NSSI between the two groups.There are few randomised clinical trials assessing interventions for NSSI in youth, and knowledge about internet‐delivered interventions is limited. Based on our results we conclude that a large‐scale trial seems feasible and warranted. Internet based intervention for non‐suicidal self‐injury (ERITA) is tested in Child and Adolescent Mental Health Services in Denmark and found feasible warranting for further investigation in a large‐scale trial. Specific Non‐suicidal self‐injury (NSSI) treatment recommendations are sparse, so this feasibility trial investigated the internet‐based therapy (ERITA) within Child and Adolescent's Mental Health Services in Denmark as a less resource demanding treatment option as add on to treatment as usual (TAU) in NSSI engaging youth.All feasibility outcomes were met: the proportion of randomized eligible patients (54%), the proportion of participants completing the experimental intervention (87%), and the proportion participating in follow‐up interviews (90%).Only a limited number of technical issues related to login obstacles occurred during the online provision of the ERITA therapy.“the deliberate self‐inflicted destruction of body tissue without suicidal intent and for purposes not socially sanctioned”   still found no difference between the group interventions on past month NSSI episodes, however, found that CDP had a faster impact on the self‐injurious behaviour  in adolescents with persistent self‐harming behavior and personality disorder traits both in individual trials  was developed  in Denmark. Before embarking on a larger pragmatic randomised trial, we investigate the feasibility of such a trial. Recent reviews specifically investigating NSSI populations, speculate that digital interventions have the greatest news value in the beginning and then lose ground, where young people lose interest and do not complete the therapeutic intervention  prior to enrollment of the first participant. The trial protocol was published prior to inclusion of the last participant, and a detailed statistical analysis plan was published before any analyses were carried out . Deidentified individual participant data (including data dictionaries) can be obtained after publication of the trial results at DNA.The TEENS feasibility trial is an investigator‐initiated randomised clinical trial in a parallel group design with blinded outcome assessment after 12 weeks intervention. The Regional Committee on Health Research Ethics in the Capital Region waived the need for approval . The trial was approved by the Knowledge Centre on Data Protection Compliance in the Capital Region  and registered at Participants were enrolled from CAMHS in the Capital Region of Denmark. Child and Adolescent Mental Health Services provides health care, free of charge based on public taxation, including in‐ and outpatient mental health treatment; referral from the primary health care sector is the norm. The recruitment period was May to October 2020 while the entire trial period, including follow‐up assessments, took place from May 2020 to January 2021.The participants were adolescent outpatients with any psychiatric disorder, 13–17 years of age, who had engaged in at least five NSSI‐episodes during the last year and at least one episode during the past month, assessed by Deliberate Self‐harm Inventory‐Youth (DSHI‐Y) Gratz, . An addiwww.ctu.dk) using a computer‐generated allocation sequence, ratio 1:1 with a varying block size of 6, 8, and 16. Both the allocation sequence and the block size were concealed from the investigators. Due to the feasibility design with a limited sample, we did not apply any stratification variables for the randomisation in this trial. The randomisation was carried out after the baseline interview, and participants allocated to the experimental group were introduced to the electronic platform of the experimental intervention.A screening procedure for NSSI was implemented in the CAMHS outpatients' services. If NSSI was present, a managing clinician briefly introduced eligible patients and their families of the opportunity to participate in the TEENS feasibility trial. Oral consent was obtained from the family to disclose contact information to the self‐injury team, who then screened for eligibility by calling the families and further introduced the trial design in more detail. Information was provided orally to all patients and legal guardians and in writing also to all eligible persons aged 15 years and above. All members of the self‐injury team are experts in the field of NSSI and experienced in child and adolescent psychiatry including in family consultations and management of mental health vulnerability in youth. Interested families were invited to an online baseline interview. Due to the Covid‐19 situation and because the experimental intervention was Internet based, all dialogue was held by telephone or online. Hereafter, eligible families  provided written informed consent and completed the electronic baseline questionnaires (see below). The randomisation procedure was handled centrally by the To prevent or minimise missing data, the participants were directed to fill out electronic research questionnaires before being able to access the treatment modules of the online ERITA platform. Text message reminders were sent automatically to participants who did not complete their weekly assessment. Prior to the follow‐up interviews, unblinded personnel accessed the research database to make sure that the electronic post‐assessment questionnaire was filled out. If not, a direct link to the assessment was sent to the participants' cell phone.Experimental intervention – The Internet based ERITA intervention as an add‐on to TAU consisting of an introduction plus 11 modules (one each week for 12 weeks) of manualized Internet based therapy. The experimental intervention includes psychoeducation, and skills training in impulse control, emotion awareness, acceptance, and validation. The format of the program consists of theoretical texts, animated films, audios, illustrations, case examples of emotion regulation theory, and interactive exercises, as well as a message function for online communication with the assigned ERITA therapist.ERITA also provides six separate modules for the parents. The parent modules provide psychoeducation on NSSI and other destructive behaviors, NSSI functions, emotional awareness, effective communication skills , and strategies to cope with the child's negative emotions in a constructive manner. For further details of the ERITA therapy and program, please see , DBT, supportive counselling, and/or psychoeducation as needed for the individual patient according to evidence‐based recommendations and guidelines applied in CAMHS  the proportion participants who completed follow‐up assessment; (2) the proportion of eligible patients who were included in the trial; and (3) the proportion of participants in the experimental intervention group who completed at least six of the ERITA modules. Completion of follow‐up assessment was defined as completing the clinical outcome of DSHI‐Y at end of intervention by telephone interview or electronic questionnaire. Eligibility was defined as those who fulfilled the inclusion criteria and proceeded to randomisation. Completion of ERITA was defined as the adolescent participants completing at least six of 11 ERITA modules as registered by session completion automatically saved on the ERITA platform by the participant once they have gone through a chapter. The rationale for this was that from module one to six, new theory and insight into self‐injures behavior and emotion regulation are introduced. Although concepts such as validation and valued direction are introduced in the second half of the treatment, these latter modules mostly serve as repetition and consolidation of what has already been taught   , and the proportion of compliance with at least six of 11 ERITA modules was 87% .p = 0.20). Similarly, no group difference was identified for most of the other explorative clinical outcomes (Table p = 0.02). We observed no difference between the two groups regarding negative event measures assessed by NEQ   while the feasibility trial was approved by the Knowledge Centre on Data Protection Compliance in the Capital Region Denmark . Following oral and written trial information electronic consent was obtained from all eligible families  wishing to participate. Age‐appropriate trial information was developed and distributed to adolescents from 15 years and older. For participants allocated to the experimental group receiving ERITA, parents had access to a pdf. with the theoretical part of the adolescent ERITA content to support the young participant, however, the parents had no access to the personal online dialogue between the adolescent and the therapist, which was confidential.https://clinicaltrials.gov/ct2/show/NCT04243603.ClinicalTrials.gov, NCT04243603. Registered 28 January 2020, Supplementary Material 1Click here for additional data file.