Functional cognitive disorders (FCD) have become a subject of increasing clinical interest in recent years, in part because of their high prevalence amongst patients attending dedicated memory clinics. Empirical understanding of FCD based on observational studies is growing, suggesting a relationship to other functional neurological disorders (FND) based on shared phenomenology. However, understanding of FCD at the theoretical level has been lacking. One suggestion has been that FCD are disorders of metacognition, most usually of metamemory. In this article, a brief overview of these constructs is presented along with existing evidence for their impairment in FCD. Previous adaptations of theoretical models of FND to accommodate FCD are reviewed. A novel application to FCD of Nelson and Narens’ monitoring and control model of metamemory is then attempted, positing an improper setting of the monitoring function, with examples of ecological relevance. Formulation of FCD in light of a metacognitive model of anosognosia is also considered. Although lacking mechanistic and neuroanatomical sophistication, this metacognitive formulation of FCD may give pointers for future hypothesis-driven research and a pragmatic basis for management strategies. The danger of words, that:Le Malade imaginaire  of 1673] in that it pretends to explain by a learned circumlocution a condition which to date neither doctors nor patients understand”.“It has been suggested … that the word ‘functional’ should be used instead of ‘hysterical’. This … is an example of the fallacy of Molière’s physician [in the play More recent commentators have also opined that “functional” is “no more enlightening” than other options, although serviceable and “accommodating in theoretical terms”. have become a subject of increasing clinical and research interest in recent years . The “fuInterest in functional disorders has encompassed the domain of cognitive, as well as sensory and motor, function Empirically, the key clinical feature of FCD, as in other FND, is a discrepancy or internal inconsistency between subjective reports and objective measures, specifically in this instance of cognitive performance, most frequently memory performance. This is perhaps best encapsulated by the observation that patients are often able, during the history-taking component of clinical assessment, to remember what they claim to have forgotten and hence are able to give an account, often detailed, of these memory lapses . The conFCD may be viewed phenomenologically as the mirror image or antithesis of the situation encountered in some patients with Alzheimer’s disease who minimize, disclaim, or “deny” any memory defect, whilst their (often anguished) relatives give a very different account, and in whom objective cognitive testing confirms evidence of amnesia. This discrepancy, the reverse of FCD, is sometimes denoted as cognitive anosognosia  or anosodiaphoria (lack of concern over the deficit), which may take a number of forms .la maladie du petit papier) [An increasing number of observational studies of FCD have been published  . Perform papier)  is commo papier)  and long papier)  term wit papier)  (for exa papier) . VariousThe development of a consensus definition of FCD , superseBox 11. One or more symptoms of impaired cognitive function.a2. Clinical evidence of internal inconsistency. b3. Symptoms or deficit that are not better explained by another medical or mental disorder. c4. Symptoms or deficit that cause clinically significant distress or impairment in social, occupational, or other important areas of functioning or warrants medical evaluation.  a. Internal inconsistency indicates a worse performance self-reported compared to objective evidence, or inconsistency between situations, or at different time points .b. Patients may have comorbid medical or psychiatric disorders as well as FCD.c. A minimum of 6 months duration should be considered. SpecifierSpecify if: with/without a linked co-morbidity.The possible relationship to, or overlap with, other FND ,15 is ofEven with this empirical information, Drury’s admonition concerning the understanding of “functional” disorders may still stand, in that a theoretical explanation is lacking. One attempt to conceptualize FCD has posited that these may be disorders, indeed primary disorders, of metacognition, in particular of metamemory ,33. BefoThe term “metamemory” was first used by the developmental psychologist John Flavell (1971) to describe knowledge about one’s memory processes and contents . FlavellClearly metamemory, like memory per se, is a multidimensional, rather than a unidimensional construct, comprising many characteristics . VariousWhilst metacognitive errors are probably not uncommon in everyday life, such as overconfidence in one’s own abilities, this may seldom result in presentation to medical services with persistent and distressing subjective cognitive complaints, which might justifiably be termed metacognitive disorder. From a clinical standpoint, a number of clinician-administered performance scales have been developed and used on occasion to assess metamemory, including but not limited to the Metamemory in Adulthood (MIA) Questionnaire , the MemMetacognition, particularly metamemory, has been examined in the context of a number of neurological disorders , includiWhat empirical support exists for the possible conceptualization of FCD as disorders of metacognition, in particular of metamemory? Currently this evidence base is limited.Using subscales of the MIA, Metternich et al. found lower memory self-efficacy in patients diagnosed with functional memory disorder than in healthy controls despite no significant differences in objective cognitive performance .The Subjective Memory Complaint (SMC) Likert Scale , in whicThe possibility that the direction of causality runs from misdirected attention to metacognitive deficits, rather than metacognitive deficits being primary in FCD, has not been entirely discounted by the empirical data . An impoThe possible relationship of FCD to other functional neurological disorders (FND) suggests that looking at existing models and theoretical frameworks for FND might inform conceptions of FCD. Whilst many psychological theories for FND have been mooted (see  for a coThe integrative cognitive model (ICM) of psychogenic non-epileptic seizures (PNES), another FND, was developed by Brown and Reuber , buildinA hierarchical Bayesian model of functional motor and sensory symptoms was developed by Edwards et al.  based onAs part of their unifying theory linking deficits in attention, information processing, and vulnerability to distraction in FND, fibromyalgia, and chronic fatigue syndrome with the proposed cognitive abnormalities in FCD, Teodoro et al. proposed a mechanistic model for cognitive difficulties across the spectrum of FCD . ThereinDixon , p. 49) 9 4,28,55A significant theoretical development in the field of metamemory was Nelson and Narens’ (1990) distinction between monitoring and control processes . FollowiThis two-level formulation was also implicit in Flavell’s earlier characterization of metacognition as referring to “the active monitoring and consequent regulation and orchestration of these processes in relation to the cognitive objects or data on which they bear” As such, this metacognitive model is easily transposed to a theoretical model of the neuropsychological mechanisms of various forms of anosognosia that was proposed by Heilman  apparen.Heilman proposed that defects in the comparator or monitoring systems may result in clinical syndromes. For example, sensory (Wernicke-type) aphasia was conceptualized as a consequence of destruction  of the neural representations of words, such that monitoring of behavioural (speech) output could not occur because there were no intact neural representations. Destruction of a monitoring system was also postulated to be one of the mechanisms accounting for the syndrome of cortical blindness (Anton’s syndrome) in which patients deny their loss of vision, along with “false feedback” to the monitor. This latter might be from visual inputs mediated via subcortical visual pathways, or from visual imagery that is misinterpreted as coming through visual input, hence accounting for the visual hallucinations that may occur in Anton’s syndrome . Although not specifically addressing the cognitive anosognosia of Alzheimer’s disease, Heilman did suggest that denial of amnesia might also be a consequence of “false feedback” to a monitoring system through the retrieval of existing memories, even if they were incorrect .In all, Heilman suggested four potential mechanisms that might account for anosognosia: impaired monitor; absence of feedback; false feedback; and improper setting of the monitor .In light of Nelson and Narens’ model of metamemory  and HeilHow is the meta-level comparator for cognitive or memory functions set, the neural representations which determine memory self-efficacy? As suggested by Herzog, commonly held negative implicit theories about ageing and memory influence perceptions of memory functioning and act as the lens though which experiences of remembering and forgetting are filtered. Moreover, this expectation of impending cognitive decline may be greater in younger than in older adults . FurtherMemory lapses and slips are a frequent occurrence in everyday life ,63. MoniIn the interest of ecological validity, it may be worthwhile to consider this model of FCD as a primary disorder of metamemory in the context of two of the most familiar complaints voiced by patients presenting to memory clinics when they are invited by the clinician to “give some examples of how your memory lets you down”: forgetting the names of familiar people; and forgetting words or what they were going to say in conversation with others. The prevalence of these complaints is not simply age-related: a study using the Subjective Memory Complaints scale  found tLearning people’s names is an example of cross-modal, non-contextual, paired-associate learning. Hence, this is material about which, once acquisition has occurred, FOK judgments can be made . HoweverForgetting what one is going to say, often referred to as losing the thread of one’s conversation, is an example of the capacity limitations of the online working memory system, and hence may be a function of attentional rather than mnemonic mechanisms. The online nature of the monitoring and control processes in Nelson and Narens’ metamemory model may be of significance here. In addition, the intentional, feed forward, prospective nature of what one is going to say might lead to a mismatch with the output if the monitoring expectations are set too high or the focus of attention is misdirected. This might also be an example of the blocking phenomena encountered when switching from implicit to explicit processing, self-focused attention leading to a deterioration in performance as in other FND . Change The previous considerations regarding the proposed adaptation of Nelson and Narens’ metamemory model to FCD are compatible with other suggested formulations of metacognition, for example, the “8 pillars of metacognition” model in which the capacities of monitoring, regulation, and adaptation of cognitive mechanisms are central . More directly relevant to FCD is the Cognitive Awareness Model (CAM)  and its There are, of course, shortcomings to the proposed theoretical metacognitive formulation of FCD. Identical to the limitations of the ICM model, as acknowledged by its authors , the proClearly the proposed metamemory model of FCD has areas of overlap with the FND models when they are extrapolated to the cognitive domain , as mighAlthough the proposed FCD metamemory model is not hierarchical like the Bayesian model of functional motor and sensory symptoms , it doesAn inferential “Bayes optimal” hierarchical system, as envisaged for perception, decision making, and sensorimotor integration , posits The proposed FCD metamemory model may be too reductive, too simplistic, and hence not able to account for or to accommodate the possible heterogeneity of FCD . The freTractatus Logico-Philosophicus §4.31) as a useful heuristic. Herein “true” and “false” are not being used as per the Wittgensteinian reportable propositions, but merely to indicate functional status, normal or abnormal, without further specification of the nature of the dysfunction. This binary classification is used here for simplicity, as it is likely that these functions are continuous rather than categorical.The suggested metacognitive formulations of FCD and anosognosia might be summarized, in the spirit of Wittgenstein, by the construction of a (modified!) truth table  and memory performance . The key point is whether mismatch  or no mismatch is detected by the monitoring comparator function, with the resulting inferences , their Some attempts have previously been made to accommodate the conceptualization of FCD as primary disorders of metacognition, principally of metamemory, within existing models of FND. Herein, it has been shown that FCD might also be accommodated within the influential Nelson and Narens’ theoretical framework of metamemory. Specifically, it has been proposed, based on analogy with models of anosognosia, that improper setting of the monitoring or comparator function at the meta-level of the framework leads to a mismatch with the output from the object-level feedback, and with the clinical correlate of the subjective memory complaint, despite a relatively preserved objective memory function. Although this proposal of dysfunction within a metacognitive feedback loop lacks mechanistic precision, nevertheless this formulation may give pointers for future hypothesis-driven research in FCD and a pragmatic basis for management strategies. Aided by an operationalized diagnostic definition of FCD , researcAt the therapeutic level, the model has clear implications for management of FCD. To adopt a computing analogy, it envisages FCD as a disorder of memory software, in contrast to disorders of memory hardware such as Alzheimer’s disease and Korsakoff’s syndrome. Since the memory monitoring function is conceptualized to be dynamic, it should be susceptible to “recalibration” or “resetting”, as occurs physiologically. Methods to do this, which might be explored in randomized controlled trials, might include modalities such as cognitive behavioural therapy and computerized metacognitive training, or even regular meditation .It is to be hoped that with increasing attention and research, FCD will become better understood and not merely, as Drury may have feared, “a learned circumlocution”


Mitragyna speciosa Korth., Rubiaceae) is a plant native to Southeast Asia, where it has been used for centuries as a mild stimulant and as medicine for various ailments. More recently, as kratom has gained popularity in the West, United States federal agencies have raised concerns over its safety leading to criminalization in some states and cities. Some of these safety concerns have echoed across media and broad-based health websites and, in the absence of clinical trials to test kratom’s efficacy and safety, considerable confusion has arisen among healthcare providers. There is, however, a growing literature of peer-reviewed science that can inform healthcare providers so that they are better equipped to discuss kratom use with consumers and people considering kratom use within the context of their overall health and safety, while recognizing that neither kratom nor any of its constituent substances or metabolites have been approved as safe and effective for any disease. An especially important gap in safety-related science is the use of kratom in combination with physiologically active substances and medicines. With these caveats in mind we provide a comprehensive overview of the available science on kratom that has the potential to i clarity for healthcare providers and patients. We conclude by making recommendations for best practices in working with people who use kratom.Kratom ( Mitragyna speciosa Korth., Rubiaceae; also known as ketum) is made from the leaves of a tropical tree in the coffee family indigenous to Southeast (SE) Asia, where it has been used for centuries as medicine for various ailments, including hypertension, diarrhea, cough, and fever  has not issued guidance or regulatory standards on kratom regarding allowable product contents, alkaloid concentrations, packaging, labeling, or marketing of kratom products that is usually provided for dietary ingredients  normally required prior to scheduling decisions was performed by the FDA, and another by an independent agency (Pinney Associates). The former has been criticized by kratom researchers for omission of important scientific studies and pertinent data, as well as inappropriate use of a computer simulation model (PHASE) that provided data that the FDA used to deem kratom an “opioid” , linkingA balanced examination of what can be drawn from the existing literature directed to healthcare providers and clinicians is warranted. This is particularly true given that the study of kratom is in its infancy: there is only one published clinical trial of kratom’s effects in humans. There is, however, a growing body of observational literature that represents a higher level of evidence than case reports or forensic toxicologists’ and medical examiners’ reports. Here, we first review research on the pharmacology of kratom and then summarize the available observational science on human kratom use in order to provide the most nuanced, accurate, and comprehensive review of kratom’s potential benefits and risks possible at this early stage of kratom research. We acknowledge that information provided here will inevitably change as more data are collected on kratom and kratom use. Like all things in science, our understanding of this plant and its use is provisional. Here we provide the most up-to-date information in an accessible manner. Based on the review, we conclude with recommendations to health practitioners for conceptualizing kratom use and working with patients who use kratom.Of the dozens of alkaloids identified in kratom, mitragynine is the most prominent , time to reach cmax, tmax (1.26–4.50 h), and elimination half-life, t1/2, (3.85–9.43 h) indicated that mitragynine was highly variable in its absorption and/or metabolism. A study using traditionally prepared kratom tea and a hydroalcoholic kratom extract given orally to rats resulted in a cmax of 63.8 and 111.9 ng/ml and tmax of 1.3 and 3.1 h, respectively, while the t1/2 was not determined  have been conducted by United States researchers revealing that unlike SE Asia, where kratom appears to be predominantly consumed by males, almost half of United States consumers are female. Also, a majority of Western consumers are middle-aged, middle-income, Caucasian, and college-educated with private insurance. Most discovered kratom through the Internet or social media, about 25% from an acquaintance/friend, and a mere 3% from a healthcare provider. Only approximately 40% informed their healthcare providers about their use . GeneralA longstanding use for kratom in SE Asia is to increase productivity. In a survey of over a million kratom users in this region, a primary motive was to enhance physical performance . This man = 2,798; A substantial portion of kratom users report using the plant to improve mood or manage symptoms associated with a mental health diagnosis. In the largest scale survey in SE Asia, many revealed using kratom to “feel better” and “cope with problems” . In a WeWhile kratom’s longstanding medicinal use in SE Asia applies to a variety of ailments, alleviation of pain is among the most common. A study in which 562 kratom users were interviewed in Malaysia revealed pain relief as a main reason for consumption . ResultsThe value of substitution (replacing an undesirable substance with a less harmful one) is evidenced by cannabis as a successful substitute for alcohol, opioids, and cocaine  or treatA convenience study sample of 136 kratom users  in an area of Malaysia known for heavy kratom use revealed that 90% were using kratom as a substitute for opioids and 84% indicated that kratom helped with their opioid withdrawal symptoms . In anotIn the West, five United States.-based internet surveys of over 20,000 kratom users, as well as over 20,000 comments to the Drug Enforcement Administration (DEA), and a survey of more than 500 people in treatment for opioid use disorder, indicate that many are using kratom as an alternative to opioids . In one a thousand or more times that of kratom  conventional uses.drugs.com, that disseminate information regarding alternatives for pain management, including kratom . Finally, the observational literature indicates that people consistently report the utility of kratom for pain relief, and this is corroborated by the only clinical trial to examine kratom and analgesia in humans.The literature on dosing is consistent, but imprecise. In general, lower doses up to approximately 5 g of raw plant material are reported to exert stimulant effects and have been compared to caffeine. Doses between approximately 5 and 15 g are reported to lead to relaxation and analgesic effects. These higher doses may be necessary for successful opioid substitution. Side effects are more likely at higher doses. Limited data show that there is variability in terms of lowest and highest perceived dose as being ineffective or effective, and that feelings of discomfort may arise from higher doses . Although no dose or dosing range can be clinically recommended, but patients can be informed that some average doses are approximately 2.5 g . The development of kratom dependence, including tolerance and withdrawal symptoms upon cessation or reduction, is more likely at higher doses and with frequent, recurring use. For this reason, patients should be encouraged to use as little as needed for therapeutic effects. People who have decided to initiate kratom use should begin with a minute amount to test for adverse reactions before slowly increasing. It is important to convey that the potency of the plant can vary based on factors such as geographical source, the season, age of the sample, and post-harvest handling , as wellGenerally, the effects of kratom last for approximately five to 7 hours, with the strongest effect within two to 4 hours of ingestion, though aftereffects  can be felt as late as the following day . One shoUnwanted effects associated with kratom use have been systematically studied. Large scale surveys and other observational studies of tens of thousands of users reveal that a minority experience dose-dependent side effects that are mostly mild and self-resolve. The most common of these are constipation, nausea, vomiting, other stomach irritation, and drowsiness . Dizzinein vitro study revealed the possibility that kratom ingestion mixed with drugs that are P-gp substrates  could lead to clinically significant toxicity . Patients looking to decrease or discontinue kratom use can be assured that this is often done without medical intervention  and thatIn order to purchase kratom that is of consistent potency and is unadulterated, patients should be informed that vendors who use Good Manufacturing Practices (GMP) are identifiable. It is also potentially helpful to inform patients about whether they risk arrest for use of kratom in a particular jurisdiction see . Finally


Despite the efficacy of psychosocial interventions in minimizing psychosocial morbidity in breast cancer survivors (BCSs), intervention delivery across survivorship is limited by physical, organizational, and attitudinal barriers, which contribute to a mental health care treatment gap in cancer settings.The aim of this study is to develop iNNOV Breast Cancer (iNNOVBC), a guided, internet-delivered, individually tailored, acceptance and commitment therapy–influenced cognitive behavioral intervention program aiming to treat mild to moderate anxiety and depression in BCSs as well as to improve fatigue, insomnia, sexual dysfunction, and health-related quality of life in this group. This study also aims to evaluate the usefulness, usability, and preliminary feasibility of iNNOVBC.iNNOVBC was developed using a user-centered design approach involving its primary and secondary end users, that is, BCSs  and mental health professionals . We used mixed methods, namely in-depth semistructured interviews, laboratory-based usability tests, short-term field trials, and surveys, to assess iNNOVBC’s usefulness, usability, and preliminary feasibility among these target users. Descriptive statistics were used to characterize the study sample, evaluate performance data, and assess survey responses. Qualitative data were recorded, transcribed verbatim, and thematically analyzed.Overall, participants considered iNNOVBC highly useful, with most participants reporting on the pertinence of its scope, the digital format, the relevant content, and the appropriate features. However, various usability issues were identified, and participants suggested that the program should be refined by simplifying navigation paths, using a more dynamic color scheme, including more icons and images, displaying information in different formats and versions, and developing smartphone and tablet versions. In addition, participants suggested that tables should be converted into plain textboxes and data visualization dashboards should be included to facilitate the tracking of progress. The possibility of using iNNOVBC in a flexible manner, tailoring it according to BCSs’ changing needs and along the cancer care continuum, was another suggestion that was identified.The study results suggest that iNNOVBC is considered useful by both BCSs and mental health professionals, configuring a promising point-of-need solution to bridge the psychological supportive care gap experienced by BCSs across the survivorship trajectory. We believe that our results may be applicable to other similar programs. However, to fulfill their full supportive role, such programs should be comprehensive, highly usable, and tailorable and must adopt a flexible yet integrated structure capable of evolving in accordance with survivors’ changing needs and the cancer continuum. Since 2020, breast cancer has been the most diagnosed cancer worldwide and the leading cause of cancer mortality in women. In Portugal, as many as 7041 women are diagnosed per year with breast cancer, and in 2020, a total of 1864 women died owing to the condition . In PortIn spite of a positive prognosis, the survivorship trajectory is frequently characterized by difficulties associated with sequelae of cancer and its treatment and late physical and psychosocial effects that hinder BCSs’ health-related quality of life (HRQoL) . AnxietyIn the past decades, several interventions have been developed to minimize psychosocial morbidity in BCSs. Recent meta-analyses demonstrated the efficacy of such interventions in improving a range of psychosocial outcomes ,14. CognInternet interventions—self-help technology-enabled interventions that provide synchronous or asynchronous health-related and mental health–related assistance based on established psychotherapy models —provide The aim of this study is to report on the development, usefulness, usability, and preliminary feasibility of iNNOV Breast Cancer (iNNOVBC), a guided, internet-delivered, individually tailored, ACT-influenced CBT program developed to treat mild to moderate anxiety and depression in BCSs, as well as to improve fatigue, insomnia, sexual dysfunction, and HRQoL in this group. Besides informing iNNOVBC’s further development and refinement, the contribution of this paper resides in the description of mental health professionals’ (MHPs’) and BCSs’ perspectives on the use of digital technology to support cancer survivors and the design implications that arise from considering these.iNNOVBC  and 2 isiNNOVBC is composed of 10 treatment modules , namely,At the onset of the intervention, BCSs using the program should tailor their treatment with the support of their assigned therapist and according to their baseline assessment and preferences. Once they reach an agreement, the selected modules should be prescribed and made available weekly to the BCSs. Then, BCSs are prompted to complete the modules in approximately 1 week. Within 24 hours of module completion, the therapists assess the BCSs’ progress based on the reported outcomes and determine whether they should proceed to the next module. When a new module is made available, BCSs receive an email notifying them. If not, therapists should instruct them on what needs to be completed to be able to advance to the next module. Integrated 2-way communication features such as email, chat, SMS text messaging, and videoconference support the intervention. The program is delivered via iTerapi, a web-based treatment platform developed at Linköping University .Mixed methods , namely The study targeted BCSs and MHPs, who are iNNOVBC’s primary and secondary end users. Eligibility criteria for BCSs consisted of women, aged >18 years, with a history of histologically confirmed breast cancer, who had completed primary adjuvant treatment , and were capable of reading and writing in Portuguese. MHPs were registered psychologists or psychiatrists, capable of reading and writing in Portuguese. A nonprobabilistic sample of BCSs and MHPs was recruited following referrals from the researchers and professionals working at treatment centers in Porto  and via snowball sampling. Participants were purposively sampled for diversity in age, academic degree, and digital technology proficiency. A total of 28 MHPs and 16 BCSs were invited to participate in the study in person, via email, or by telephone. Of the invited individuals, 54% (15/28) of the MHPs and 88% (14/16) of the BCSs agreed to participate. Meaning saturation was used as a stopping criterion, which meant that new participants would not be enrolled once novel fieldwork insights stopped changing analysis significantly . Data coData were collected between November 2019 and February 2020 . Up to 2 to 3 interviewers or moderators  participated in data collection. The research protocol included an exploratory semistructured interview  for MHPs and 74 minutes for BCSs (range 39-106 minutes). Usability tests were completed on average in 20 minutes and followed by 28 minutes (range 10-46 minutes) of debriefing interviews. Interview recordings were transcribed verbatim (CMS and Ana Alves) in parallel to data collection, using oTranscribe  . UsabiliBackground questionnaires tailored to each target group collected clinical, sociodemographic, and internet-related characteristics. BCSs were inquired about age, gender, education level, marital status, occupation, professional status, distance between residence and treatment center, time since diagnosis, type of treatment performed, survivorship status, proficiency using digital technology, and experience in using digital mental health (DMH) programs. MHPs were inquired about age, gender, education level, marital status, occupation, professional status, work context, professional experience (in years), theoretical orientation, proficiency in using digital technology, and experience in using DMH programs.Semistructured interview guides  were devWe conducted usability tests and analyzed the performance and acceptance of the system. To assess performance, task analysis was conducted and the number of completed tasks, errors, and assistances were recorded in observation grids . AcceptaThe preliminary feasibility of the program was assessed via debriefing semistructured interviews and assessment questionnaire in iNNOVBC’s treatment modules . The parA combination of quantitative and qualitative methods was applied to assess iNNOVBC’s usefulness, usability, and perceived feasibility. Descriptive statistics, namely, counts, percentages, medians, and IQRs, were used to characterize the study sample, evaluate performance data, and assess preference data collected via the System Usability Scale and the treatment modules’ assessment questionnaire. No efficiency metrics were computed because the think-aloud method was applied. Microsoft Excel was used to compute quantitative variables. Qualitative data resulting from the interviews and BCSs’ written comments were transcribed verbatim and analyzed using the thematic analysis method of Braun and Clarke . First, The sample comprised 24 participants , includiThe subsample of MHPs was composed of 15% (2/13) psychiatrists and 85% (11/13) clinical psychologists. Most professionals were female , and their median age was 35 years . The median of MHPs’ professional experience was 11 years (IQR 11). Moreover, 92% (12/13) of professionals were active, and 30% (4/13) worked in psycho-oncology services. Approximately half of our sample  held a CBT orientation. Considering participants’ proficiency in using digital technology, most professionals  classified their skills as medium. Approximately half of professionals  reported previous experience in using DMH programs.iNNOVBC’s perceived usefulness was assessed during the interviews conducted before and after the usability tests and by surveying field trial participants on the usefulness and adequacy of the program’s modules. During the field trials, the content of the modules living with breast cancer and beyond , anxiety , relaxation , sleep , and fatigue  were appraised, with all being rated with 5 (out of 5) stars by BCSs evaluating it. Overall, participants found the program’s approach, content, and features as highly relevant and useful. BCSs classified the content of the modules as very useful  or extremely useful  and very adequate  or extremely adequate  in addressing their difficulties and needs. Only 13% (1/8) of the participants reported that the relaxation module was neither adequate nor inadequate to her needs. All survivors  reported that they would recommend the modules to a friend or family member going through the same condition.Considering the role iNNOVBC could play in BCSs supportive care, both survivors and professionals considered iNNOVBC could have a significant impact in supporting BCSs throughout the cancer continuum:There were a lot of doubts, fevers, discomforts, disquietudes...there still are...and if I had this type of resource, I could have used it instead of googling or looking into patient groups, for some kind of answer...Because you do feel the need to go to forums and ask, does anyone feel like this? What have you done? And if there were a platform like this, the type of support provided would be different, more credible and appropriate.BCS11Similar to BCS11, most participants valued the possibility of accessing “trustworthy” (BCS6) self-care information provided “anytime, anywhere” (BCS7) via iNNOVBC. The interviewed BCSs had searched on the web for information on treatments’ adverse events, practical strategies, and emotional challenges they were faced with, but their searches were lengthy and required them to assess the quality of information they were presented with. Both BCSs and MHPs considered that having “easy access to evidence-based ready to use psycho-educational content” (MHP10) could help survivors better manage their condition and problems.According to the participants, the survivorship trajectory is characterized by many biopsychosocial challenges that deeply impact survivors’ well-being. Several participants described the pervasive and long-lasting impact that treatment’s adverse events or sequelae had on their physical and mental health, underlining the importance of receiving accurate and comprehensive information about it. Effects such as alopecia, onycholysis, pain, menopausal symptoms, fatigue, cardiotoxicity, lymphedema, osteoporosis, infertility, and memory loss were often discussed by interviewees as key information points to address in a nuanced and dynamic manner. During the course of treatment, various survivors received flyers and booklets about treatments’ adverse effects, but most complained about their unappealing design and low intelligibility and focus on the active treatment stage, therefore failing to provide a continuous perspective on its management after treatment completion. The fact that iNNOVBC approached many of those themes “in a chronological way” (BCS1) was appreciated by various BCSs because it enabled them to prepare and cope with it in the long term.The impact of cancer and its treatments on survivors’ emotional health was another matter of concern. Both MHPs and BCSs underlined the importance of providing psychological support to BCSs throughout the cancer continuum, particularly during the transition from active treatment to follow-up care:Getting psychological support is very important at all stages...at the diagnosis, during treatment and after treatment...People are not aware of this, they tend to say “Ah, that’s over now!” and expect us to return to whom we used to be...But that’s not possible...you still need support. This feels almost like...a post-traumatic situation...and by saying that it’s almost like they’re taking away your legitimacy to feel the pain, so it can feel very isolating to cross that path.BCS2It’s an abrupt shift from being extremely cared for, from having that unconditional support during chemo to stopped being cared for...As soon as your hair starts to grow, everyone assumes that everything is fine. But it’s not. I will never be able to say again that I’m fine. I’m not healed, I’m full of fears, anxiety, and sorrow. So...it was extremely hard for me to deal with that because I felt abandoned...people had pulled the rug out from under me.BCS7Similar to BCS2 and BCS7, various participants discussed the experience of feeling in distress and unsupported after finishing the primary treatment. Problems such as “dealing with low mood” (BCS11), “feeling anxious all the time” (BCS2), “fearing that cancer had returned” (BCS8), or fear of “dying” (BCS9) were common, often impacting BCSs’ sleep and interpersonal relationships. Difficulties in adapting to a “scarred body image” (BCS5) were also prevalent in interviewees’ narratives and various participants reported on the profound impact it had on their self-esteem, sexuality, and intimate relationships:Losing my breast shook my self-esteem, it shook everything...it’s hard to live without it, I’m a woman. I...I’m incapable of being naked in front of my husband. I feel embarrassed...I’m not able to hug him anymore. I’m afraid he feels that it’s not my breast, that it isn’t real. I sleep...without the prosthesis, but I always try to sleep with my back to him and when I realize I’m facing him, I turn over right away...I’m afraid that if he sees me, he might lose his interest in me, that he stops desiring me. ...We still have sex but it’s not the same. I’m always afraid that he touches where he’s not supposed to...I do not lean against him...I avoid his touch. It’s difficult and...I know that there are women that deal with this well, but I...I do not.BCS9Similar to BCS9, various participants talked about not being able to adapt to their changed self, feeling like a fake version of themselves, incapable of restoring lost intimacies, and isolated by the “tabu cancer had become” (BCS2) in their inner circles. Coping with such problems was highly demanding, and many struggled to discuss such topics with friends, family, and professionals owing to their sensitive nature. Thus, many interviewees appreciated the “assertiveness of the themes” (BCS6) explored at iNNOVBC and the possibility of receiving professional support at a distance or without face-to-face contact:It’s important to have support but it’s uncomfortable to talk about these issues face-to-face...Maybe through this platform, it could be easier...I believe I could feel more comfortable to ask some questions if I knew this was anonymous, if I didn’t have to identify me...I believe it would be much easier to approach intimate topics via chat or e-mail than in-person.BCS3Participants such as BCS3 appreciated the fact that iNNOVBC allowed direct communication between MHPs and BCSs. Both professionals and survivors considered having chat, email, and videoconference communication alternatives to be helpful. By offering synchronous and asynchronous communication channels associated with different degrees of exposure, participants considered that iNNOVBC “could promote survivors’ self-disclosure” (MHP6) and facilitate the “timely discussion” (MHP4) of sensitive topics, ultimately, “benefiting the therapeutic process” (MHP12). They also saw advantages in the possibility of automatically sending psychoeducational content and scheduling and notifying BCSs about tasks and questionnaires to be completed along the implementation of the program:The functionalities are well thought and the fact that everything is integrated is awesome...this combines a modular treatment approach with videoconference and chat...it allows you to take notes...and the instruments are embedded...That’s awesome and exactly what I need in my practice!MHP5The fact that iNNOVBC combines evidence-based content with communication, monitoring, and documentation features was praised by various professionals. The interviewed MHPs considered that it could reduce the time and effort they need to invest in finding, preparing, and assessing materials, enabling them to work more efficiently. iNNOVBC was also considered useful to promote “continuity of the relationship established between the therapist and the client” (MHP7) beyond appointments. Most importantly, by doing so, iNNOVBC could configure a point-of-need service that could support BCSs along the survivorship trajectory. Nevertheless, it is important to say that iNNOVBC’s usefulness could be compromised by its “lack of intuitiveness” (MHP9).Both the quantitative and qualitative data collected during the usability tests and interviews identified design and functionality issues that could be improved to enable more effective and efficient use of iNNOVBC and increase users’ satisfaction with the program. In general, participants’ effectiveness, as measured by completion rates, was high in both groups , whereas other interviewees suggested that a tour providing an overview of the platform or adding labels and preview options to most used functionalities would suffice. Furthermore, the use of familiar and interactive design was also appointed as a strategy that could facilitate navigation:I found it a little monotonous, everything looked the same...and that confused me. Maybe using more colour and highlighting some parts...it would be easier to understand how the materials are organized....BCS6Similar to BCS6, various participants expected to find a more appealing and dynamic color scheme, as well as greater use of icons, images, and shortcuts. Despite the perceived adequacy of the content materials, the presentation of long text, sometimes displayed along various binders and features, was considered problematic. Various participants had to do a strenuous effort to screen through the available information and complete the usability test tasks. As a result, participants often became frustrated and some verbalized feeling discouraged to use the program:I find the anxiety module content very clear, easy to read and very interesting for anxiety sufferers...but the program, in terms of presentation, requires some improvements because sometimes the information displayed is too much.BCS2Not only from the therapists’ perspective but also from the patients' there are things that should be simplified so that they do not experience the same frustration I felt because they would give up on using the program...Instead of making it easier, I am afraid they would have to press so many buttons, that they would not understand what is expected from them, and they would give up...ending up not sending anything.MHP3Corroborating MHP3, various participants mentioned that simplifications to the provided materials should be performed. Participants suggested organizing the information more concisely, in accordance with single themes, providing hyperlinks to additional information whenever necessary. Participant BCSs also underlined the importance of simplifying the exercise worksheets owing to difficulties in handling tables , suggesting that information should be entered using plain textboxes:It should have an option to enter the date and then the system would label it as register 1, 2, 3, etc...automatically. This shouldn't be a table, it should be a simple field to complete and then the psychologists would see the table. If it's important to the patient to see the progress, a different graphical approach should be used...considering that there are a lot of items to be filled in the platform, I believe having a summary, and overview...that helped me realize my progress...maybe presented as a graph, not only in writing...and something beautiful to see...would make me feel, you know?...Wow, I managed to get here today...As children have at school, the green, yellow, and red stars...Maybe I’m being childish...but for those who are at this stage...Positive reinforcement is needed....BCS11Similar to BCS11, the MHPs participating in the study also recommended the integration of data visualization dashboards into the program. Professionals considered the inclusion of a “simple dashboard providing digested information about specific scores, or cut-offs being exceeded or any tasks or questionnaires pending” (MHP7) would facilitate the handling of the program and BCSs’ treatment progress follow-up. The inclusion of gamification principles was also mentioned as interesting by a few MHPs, owing to its potential of promoting engagement to treatment in BCSs.utilizadores, treatment modules/módulos de tratamento, and worksheets/Fichas de trabalho) and a perceived lack of integration between some sections of the platform was also a matter of concern. Various participants struggled to grasp iNNOVBC’s affordances because the designations used were unfamiliar to them. Moreover, various participants verbalized difficulties in learning and remembering how to navigate from the user hub or the treatment modules section to the conversations section and vice versa. During this process, errors were recurrent, and many participants opted for a trial and error or a go to landing page strategy to complete the proposed tasks. These difficulties hindered not only participants’ effectiveness and efficiency but also their satisfaction with the program:The use of unfamiliar terminology , and between alternative versions of the same material  was considered important to make the program more inclusive and engaging:Audios and videos...If the person doesn’t want to read or has a lot of difficulties in understanding, that could help...and, the way I see it, this shouldn’t be an obligation, but an app that is available to help me and to be used according to my needs. For example, the relaxation...I am working on my sleep isn’t it, controlling my sleep and then I could access the other menus like...Now I am going to relax for a while, and then have the exercise 1, 2 and 3 and...ok, today I’m going to use this one....BCS8Maybe I like having more control...But I believe it’s important to me to be able to decide which module a specific patient should be working with in a particular week...Depending on what I think that makes more sense to the person at that specific time...or to be the client herself deciding what makes more sense...I believe that for this to be accepted in the future, professionals must have the possibility of adding information or questionnaires themselves. I think that’s important, to make them feel this is a valuable tool and not to reject it.MHP13à la cart platform or self-care toolbox, where different content and strategies could be prescribed simultaneously or used as needed. This was also clear from the participants’ behavior during the usability tests, where sometimes errors were committed because participants assumed that modules  could be used interchangeably and not sequentially. This discrepancy between the program’s original concept and how participants appropriated the program or intended to use it was emphasized during the field trials, impacting participants’ perception of iNNOVBC’s feasibility.Similar to MHP13, various participants mentioned the intention to use the program as an Many participants reported that integrating iNNOVBC into their routine, as prescribed, would be feasible but challenging. MHPs worried about the implementation of the program at their workplaces owing to interoperability as well as practical and attitudinal limitations, whereas BCSs anticipated difficulties in “finding the time to fit the program into the day-to-day life” (BCS1):Considering the hustle of professional life, I believe it wouldn’t be easy for me to comply with everything that is asked...to enter the site and make daily registrations because I would have to be available to complete several steps and to pay close attention to it. Nowadays, people want simple, fast, and short tasks...and as is, I am not sure I would be able to do it straightforwardly.BCS6It is important to me to have some flexibility...I don’t want to make this another chore that I have to do. I think it would make me even more stressed because I would be worried about complying...I don’t want it to be another obligation.BCS3As mentioned by BCS3 and BCS6, various interviewees underlined the role that flexibility, accessibility, and ease of use could play in iNNOVBC’s uptake. During the field trials, various participants used iNNOVBC on their smartphones, owing to its portability and usability. A participant who was retired justified that she did not “use computers in a long time, being more acquainted with mobile devices” (BCS4). Another participant who was on sick leave mentioned not using computers regularly, because she did not usually carry it with her anymore and some “movements, like pulling the plug or pressing the mouse buttons, still hurt due to hormonal treatment” (BCS9). Another working participant revealed being receptive to use the web version of the program but showed some resistance in spending additional hours in front of the computer while at home (BCS10). However, as iNNOVBC runs on a responsive web-based platform, some materials did not perfectly adapt to their mobile devices and some exercises such as the relaxation audios were interrupted by notifications, thereby compromising the delivery of the intervention. Thus, some participants reported it would “be easier to have it in app format” (BCS11), suggesting that this is a more convenient and accessible format for BCSs.Another important aspect discussed by BCSs as possibly facilitating adherence to the program concerned having a direct communication channel with psychologists:Having a psychologist on the other side of the screen is particularly important...Sometimes you need to listen to someone assertive to be able to keep going...If this were like an online helpline like SNS24  but for psychological issues, I would use it often. If I saw it was reliable and that it helped me, I believe I would use it several times, because I missed that support.BCS7Having timely feedback on what to expect or about what is considered normal and not having to wait for the next appointment could be very important to better manage the emotional impact of cancer, making me interested in using this.BCS10The possibility of posing doubts; discussing difficulties associated with the treatment, follow-up, and discharge processes; and receiving professional feedback from psychologists was valued by most BCSs. Interestingly, survivors seemed to conceptualize iNNOVBC not necessarily as a structured psychotherapeutic approach but as an on-demand tangible supportive tool that could provide them with access to tailored content and psychological support timely delivered according to the specific moment of the survivorship trajectory they were at. According to participants, both information and supportive care needs change significantly along the survivorship continuum and having access to such a tool could secure them that they were “still being taken care of” (BCS1) during the follow-up stage.However, to fulfill its full supportive role, besides performing some simplifications to the program, most participants considered that some sort of training should be provided to both MHPs and BCSs. Participants considered that having access to training material in graphical, written, or video format would facilitate the use of the program. In addition, some MHPs mentioned that considering the novelty of the programs’ approach, the provision of training sessions and on-job training would be advisable not only to present the platform but also to introduce therapists to the program’s rationale and components:It is important to know more about the program, how it was created and that it really works. It would provide us with more confidence in using the program if we knew we would not be wasting our clients’ time and money.MHP9I believe training should be an extended version of what we have done here today [usability test], with practical situations and instructions, so we can clarify our doubts...like a workshop session...and then having someone there to help us during the first weeks....MHP12The positive impact of having dedicated professionals, conceivably digital navigators, supporting the implementation of the program was also discussed by BCSs. Some participants considered it would be important to have an appointed professional to introduce them to iNNOVBC’s content, structure, and features, at their cancer centers. Such support could help them in overcoming usability issues and attitudinal barriers toward the program and, ultimately, facilitating adoption:After being admitted or having a first appointment with the doctor, he could say “now you are going to meet a colleague of mine, that will show you how to use a tool that can help you deal with your situation” and then the designated colleague, that has to be an appealing person, possibly a psychologist to better know how to convey the information to the person, would explain the purpose of the program, show how the program works and even trial it with the patient...in the beginning, they might think “this is boring”, but If people are properly introduced [to the program], later, when they are feeling more anxious, they might remember “Ah, I have that app that can help me 24/7” and they would value the support that is provided in here.BCS8iNNOVBC was regarded as part of a comprehensive portfolio of services to be provided by cancer centers to BCSs, to which they would have to be informed about, introduced to, and properly referred to, to be able to use it at its full potential. Similar to BCS8, some MHPs thought that oncologists could play a significant role in facilitating iNNOVBC dissemination and uptake in cancer settings. As physicians “are the ones orchestrating treatment” (MHP5), they were viewed by participants as important gatekeepers of programs such as iNNOVBC. However, some MHPs mentioned that oncologists could not necessarily be “receptive to prescribe it, due to their biomedical approach...and lack of involvement in the delivery of psychosocial interventions” (MHP2). Thus, for iNNOVBC to become part of survivors’ “adjuvant supportive care” (MHP1) and for it to be properly integrated into clinical settings, some MHPs considered that training should be extended to other professional groups, such as nurses, physicians, and managers working within oncology. To be successfully implemented, iNNOVBC would have to be recognized as a valuable service to be provided by the several actors playing in the cancer setting.In this study, iNNOVBC—a guided, internet-delivered, individually tailored, ACT-influenced CBT intervention aiming at treating mild to moderate anxiety and depression as well as improving fatigue, insomnia, sexual dysfunction, and HRQoL in BCSs—was developed with a user-centered design approach  and explOverall, participants considered iNNOVBC highly useful, with most interviewees reporting on the pertinence of its scope, digital format, content, and features. Consistent with the literature , particiAnother important aspect contributing to participants’ perception of the usefulness of iNNOVBC concerned the multifeatured and integrated nature of the program. Participants appreciated the fact that iNNOVBC combined psychoeducation, communication, documentation, and automatized scheduling and notification features, allowing a more efficient and comprehensive assessment and follow-up of BCSs. Furthermore, the possibility of MHPs and BCSs to communicate synchronously and asynchronously  through the platform, as well as in accordance with different degrees of personal exposure, was valued by various participants. Some participants mentioned that using chat or email could facilitate self-disclosure in BCSs and promote the timely discussion of sensitive topics often avoided, thus having a positive impact on the established therapeutic alliance and process. Nevertheless, few studies have addressed chat-based internet interventions targeting cancer survivors. Previous research has focused on chat groups for patients with prostate cancer  or adoleDespite participants’ perceived usefulness of iNNOVBC, both BCSs and MHPs identified aspects hindering their experience while using the program and changes to be performed to achieve better effectiveness, efficiency, and satisfaction with iNNOVBC. These included refining the program’s aesthetics by using a minimalist and recognizable design; improving interaction design by making the navigation within the program more consistent and constrained; decreasing the cognitive overload experienced by participants by using terminology tailored to each context of use and balancing the amount of information displayed; increasing the feedback provided to users, so that they are continuously informed about the impact of their work within the program; and diversifying the media used for intervention delivery by developing smartphone and tablet versions of the program. These findings echo many of the limitations and development requirements gathered in previous research aimed at developing digital programs for supporting cancer survivors ,65,68-73In particular, BCSs and MHPs participating in this study requested the simplification of navigation paths, suggesting that the use of an opening dashboard would facilitate the understanding and handling of iNNOVBC. Adding labels and preview options to the most used functionalities was also considered important to increase the discoverability of the program. Likewise, the use of a more dynamic color scheme and greater use of icons, images, and shortcuts were appointed as necessary to facilitate the recognition of the program’s affordances and facilitate its use. Previous research has yielded comparable results ,65,69-71my progress page to display didactic content and tools that had been completed and chart anxiety scores to facilitate tracking of progress. Nevertheless, and according to Kuijpers et al [Moreover, participants underlined the importance of balancing and diversifying the information that is displayed at each given time, as well as simplifying data entry tools. According to participants, information should be grouped more concisely , delivered using various media , and displayed in different formats  and versions  and should allow entering data using plain textboxes instead of tables to make the program more inclusive and easier to use. Complementarily, the integration of data visualization dashboards providing digested information on completed or to-be-completed tasks and questionnaires, its scores, and cutoff points being exceeded or achieved was appointed by interviewees as relevant. Participants anticipated that such a strategy could facilitate the handling of the program and the assessment of BCSs’ treatment progress, promoting their engagement with iNNOVBC. Previous research corroborate these findings -73. In ars et al , althougThe option to tailor iNNOVBC along the cancer continuum was a salient development requirement identified during this study. Being conceived as an individually tailored program, iNNOVBC permits some degree of tailoring, namely, in what concerns the treatment modules. However, participants considered further layout and content customization should be allowed so that the program could adapt to the idiosyncrasies of each of the survivorship trajectory stages. Participants considered that comprehensive support should be provided along this continuum, not compartmentalizing survivors’ needs but shaping and transforming the program according to its evolution. Similar to a rhapsody, iNNOVBC should adopt “an episodic yet integrated, free-flowing structure, featuring a range of highly contrasted moods, colour, and tonality” , to be uà la cart platform or self-care toolbox, where different content and strategies could be prescribed simultaneously or used as needed, and not in a prescriptive manner, evidence suggests that the implementation of structured approaches, theoretically grounded and validated to specific contexts of use, best serves survivors [However, such an understanding of the program contrasts with its original concept and theoretical grounding. Although participant survivors mentioned the intention to use the program as an urvivors ,14. Thisurvivors  as potenurvivors  not onlyurvivors . The resThis study presents various strengths and limitations. Strengths of this study include the adoption of a user-centered design approach combining mixed methods  that were used to explore the usefulness, usability, and preliminary feasibility of iNNOVBC in a comprehensive manner. Furthermore, the study was conducted by an interdisciplinary team and involved iNNOVBC’s primary and secondary end users, that is, BCSs and MHPs, benefiting from complementary input by these stakeholders. In addition, participants have been purposefully sampled for diversity in age, academic degree, and digital technology proficiency. Limitations include a small sample size and minimal diversity in participants’ educational level and experience in using DMH programs. Moreover, participant BCSs were younger in the current sample than the general Portuguese BCS population , and parThe results of this study hold important implications for the further development and implementation of programs such as iNNOVBC. First, DMH programs targeting cancer survivors could benefit from the early involvement of its primary, secondary, and tertiary end users in the development process. By involving survivors, health care professionals, and managers in codevelopment activities , interventions could be designed to address stakeholders’ real needs and development could better align with their practices and contexts, thereby increasing the odds of successful implementation. Second, involving interdisciplinary teams in the development process is key to ensure that comprehensive solutions are developed and design caveats are timely anticipated, identified, and refined, thus not compromising the usefulness, usability, and feasibility of such programs. Third, DMH interventions must be conceived as supportive point-of-need services capable of adjuvating and extending cancer care delivery. Programs must adopt a flexible yet integrated structure capable of being continuously tailored to end users’ changing needs, evolving along the cancer continuum. In this context, transdiagnostic programs might be particularly useful in fulfilling this requirement. Finally, implementation research must be conducted to determine the effectiveness of developed programs and identify service delivery bottlenecks  to which fast-track solutions  must be developed and tested.This study explored the usefulness, usability, and preliminary feasibility of iNNOVBC, and its results suggest that DMH programs, such as iNNOVBC, are considered useful by both BCSs and MHPs, thus configuring a promising point-of-need solution to bridge the supportive care gap experienced by BCSs across the survivorship trajectory. However, to fulfill its full supportive role, such programs must be comprehensive, highly usable, and tailorable and adopt a flexible yet integrated structure capable of evolving in accordance with survivors’ changing needs along the cancer continuum.


Controlled vocabularies are fundamental resources for information extraction from clinical texts using natural language processing (NLP). Standard language resources available in the healthcare domain such as the UMLS metathesaurus or SNOMED CT are widely used for this purpose, but with limitations such as lexical ambiguity of clinical terms. However, most of them are unambiguous within text limited to a given clinical specialty. This is one rationale besides others to classify clinical text by the clinical specialty to which they belong.This paper addresses this limitation by proposing and applying a method that automatically extracts Spanish medical terms classified and weighted per sub-domain, using Spanish MEDLINE titles and abstracts as input. The hypothesis is biomedical NLP tasks benefit from collections of domain terms that are specific to clinical subdomains. We use PubMed queries that generate sub-domain specific corpora from Spanish titles and abstracts, from which token n-grams are collected and metrics of relevance, discriminatory power, and broadness per sub-domain are computed. The generated term set, called Spanish core vocabulary about clinical specialties (SCOVACLIS), was made available to the scientific community and used in a text classification problem obtaining improvements of 6 percentage points in the F-measure compared to the baseline using Multilayer Perceptron, thus demonstrating the hypothesis that a specialized term set improves NLP tasks.The creation and validation of SCOVACLIS support the hypothesis that specific term sets reduce the level of ambiguity when compared to a specialty-independent and broad-scope vocabulary. Information extracted from clinical narratives has been used for a wide range of biomedical applications –4, and nMost of these studies rely on controlled vocabularies (CVs) in different flavors, known as dictionaries, lexicons, terminologies and ontologies. They arBiomedical CVs have known drawbacks: some of them have a broad scope , but lack the granularity required by particular clinical specialties or services. Others are restricted to a specific semantic category like diseases or drugs. Even those that provide good conceptual coverage of a domain, often lack sufficient lexical coverage, in particular for languages other than English. In fact, some studies have found out that semantic features recognized using CVs in clinical narratives are useless for some classification problems, probably because they are too broad . BecauseThe predominance of the English language in biomedical publications is reflected by the fact that many CVs are restricted to English, whereas others have only partial translations to other languages. The Unified Medical Language System UMLS , 26 has Considering the availability of terminologies suited to cover a given clinical specialty in a certain natural language, a way to effectively apply NLP and ML technology to clinical narratives is to extend the scope of specialized language resources that are openly available for international and multilingual communities. Such resources are expected to accelerate the development and use of NLP and ML technology in the clinical domain, and to reduce the complexity of NLP tasks that deal with the severe problem of semantic  ambiguity, particularly in tasks like concept extraction , co-refeThis study scrutinizes the aforementioned problem from a Spanish language perspective. With its several dialects and varieties, Spanish is an official language in about 20 countries and is spoken by around half a billion people. Our source for Spanish is content from the literature database PubMed, for which we have proposed a method for automated harvesting medical term sets that are highly specific for a clinical specialty. Clinical specialties are subdivisions of the field of health care, such as represented by institutional divisions in health facilities, by fields of clinical research, and by undergraduate and post-graduate medical curricula. Instances of specialties are neurology, pathology, radiology, surgery and internal medicine, among many others, with sub-specialties like nephrology, diabetology, etc. There is no world-wide standard of clinical specialties, which explains high variations regarding subdivision of and overlaps between specialties.The focus of this study is the development of a method for extracting lexical content from PubMed records, tagged by clinical specialties, and the creation of lists of terms that are specific for each specialty. The rationale is not to produce vocabularies that replace existing controlled terminologies but to support the production of specialized term sets, mainly for text classification purposes.An additional contribution of this paper is to customize existing CVs to clinical specialties. This is the reason why we created SCOVACLIS .1Clinical sublanguage aspects have been addressed in many studies. Some of them identified differences in lexical and semantic patterns used within clinical specialties and types of clinical authors , 31, sucAn early example is a method proposed by Bernhardt et al. , which iIn order to identify redundant information across specialties and clinical settings, Zhang et al.  automatiFinally, some studies , 34 applHarvesting vocabulary from biomedical literature has been subject to many studies in biomedical NLP research. In an early review, Krauthammer and Nenadic  distinguA method for extracting terms in a molecular biology context was described by Takeuchi and Collier . The extFor languages other than English, Marciniak and Mykowiecka  harvesteFinally, Sandoval et al.  created viz. the construction of sets of terms that are maximally specific to clinical specialties. Such term sets can be useful for document classification, but also for adding new content to existing CVs. Our technique can be applied to any language as long as the related PubMed records include enough titles and links to abstracts in the original language. Subsequently, we will suggest a refinement for the term identification task, for which different statistical measures will be proposed in order to improve the selection of candidate terms. These measures are based on the importance of each term in each specialty and its importance in the overall corpus. Finally, this list of terms is used as an extra feature in a multi-label classifier.In this paper, we focus on the use of NLP techniques and tools for harvesting Spanish vocabulary from PubMed for a specific goal, frequent in and specific for a clinical specialty, thus resulting in a maximally characteristic term set for each clinical specialty. The balance between term frequency discriminative power then would result, e.g., for clinical oncology, in the selection of the important and frequent terms “carcinoma” and “tumor”, but also of less frequent, but highly specific terms like “leucemia mielomonocítica” or “dermatofibrosarcoma”. The main phases of this method are depicted in Fig. The method was designed to extract terms that are both The first phase of our method is the acquisition of domain corpora classified by clinical specialty cf. "" sectionThe second phase cf. "" sectionThe last phase, term consolidation cf. "" sectionn). L refers to the number of specialties per hierarchical level. Out of 129 specialties, 45 belonged to the first level (L1) and 65 belonged to the second level (L2) of the hierarchy.Figure For defining the set of clinical specialties, the method starts extracting the branch of the MeSH thesaurus under “Disciplines and occupations” > “Health Occupations” > “Medicine” (Step 1).Most subcategories obtained under this branch are clinical and paraclinical specialties, but others on education, research, epidemiology, or public health, were considered out of scope because they do not produce routine, non-research, textual content in health care scenarios (Step 2). Examples are “aerospace medicine”, and immunochemistry . Another category considered as non-specialties, such as “clinical medicine”—an umbrella term for all clinical specialties, but in fact, it is orthogonal within the taxonomy, including “precision medicine” and “evidence-based-medicine” - none of them being clinical specialties that would produce a distinct kind of textual data and therefore be relevant for specific vocabulary generation. So, this branch was excluded as well.Subcategory selection was the only step done manually, given the resources available, the inherent complexity of subdividing clinical specialties, the idiosyncratic nature of the division of the medical realm and the apparent lack of principled modeling of the specialty subtree in MeSH.S and is, therefore, relevant for term extraction if it fulfills one of the following conditions:S.The affiliation of the first author corresponds to an institution or department associated with S.The article was written for a publication in the area of S.The article was categorized using keywords relevant to S.The article was indexed with MeSH terms relevant to The rationale behind these criteria is that the articles that contain specialty-relevant terms are rarely ever indexed with a MeSH term from the clinical specialty subtree. E.g., “RF-New Recombinant Vaccine for the Prevention of Herpes Zoster” is an article relevant for dermatology, but it is not annotated with the MeSH term “Dermatology”. This is also obvious when counting only 20,000 articles indexed with the MeSH term “cardiology”, opposed to 830,000 ones with the word “heart” in title or abstract. Following our goal, we exclusively analyzed Spanish content; a mandatory condition is that the PubMed record contains at least a Spanish title.Out of this specialty selection, we generated the queries for retrieving specialty-specific PubMed content (Step 3), under the assumption that a text belongs to a clinical specialty Our query generators Step 3) performed PubMed queries using Biopython  for extr performeMedicina General for the MeSH ID D058006.In order to expand our query further, we added for each of these terms  Spanish MeSH translations retrieved from the UMLS Metathesaurus, marked as MSHSPA. E.g., the MeSH term “General Practice” is expanded by Despite the possibility to obtain more related terms like synonyms and term variants for describing a specialty, we decided to restrict ourselves to a limited set of cue terms that optimally delineate the scope of a clinical specialty. This strategy should maintain a high precision regarding the goal of our study, i.e. harvesting specific terms. It also allows easy reproduction of the query generation by using the UMLS Metathesaurus only. An example of the automatically generated query that selects dermatology content is the following:Has Spanish(SPA) as document language (LA).Contains “dermatology” or “dermatología” in at least one of the following fields: translated journal title (TA), title or abstract translated to English (TIAB), corporate author (CN), secondary source (SI), as keyword set by the author (OT), in some affiliation (AD), in MeSH Terms (MH:noexp) or MeSH Subheadings (SH:noexp).Finally, we include the terms “See Also”, in this case “Skin Diseases”, in the query to search for them in the MeSH terms [MH].2Since many sub-specialties share the terminology preferences of the specialty from which they are derived, our method integrates terminology extracted from more fine-grained specialties to entries belonging to a higher level in the specialty hierarchy (Step 4).The following PubMed query demonstrates our interest in retrieving Spanish content from dermatology by selecting the following fields and values in the PubMed record:Harvesting important terms that are highly specific for a specialty requires a considerable amount of text. The number of required texts may vary according to the diversity of terms for each specialty; however, a minimum amount of texts is desirable. For this reason, the process removes all second-level specialties with less than 1000 Spanish titles (Step 5) and then maintains only one specialty when it has duplicates, which means that it belongs to more than one MeSH subtree (Step 6). This happened with“Gynecology”, belonged to both the MeSH subtree “Reproductive Medicine” and “Specialties, Surgical”. The final step 7 eliminates specialties in the first level that have not yet achieved a significant amount of content.From the final set of titles and abstracts per specialty, those with “case reports” as publication type were retained to be used as evaluation benchmark (i.e. test data set). The reason was that case reports seem to use a language that is closer to clinical narratives. Case reports typically document interesting observations on individual patients, e.g., new syndromes, particular and unusual evolution of diseases (often orphan diseases), complications of common treatments as well as beneficial or adverse effects of common or unusual therapies .Once we obtained a collection of Spanish titles and abstracts per specialty, all texts were then submitted to a process that extracts possibly relevant terms.n between 1 and 3. E.g., from “Manejo práctico de inmunosupresores en dermatología”, the unigrams extracted are: Manejo, práctico, de, inmunosupresores, en, dermatología. The bigrams extracted are: Manejo práctico, practico de, de inmunosupresores,inmunosupresores en, en dermatología. The trigrams are: Manejo práctico de, practico de inmunosupresores, de inmunosupresores en, inmunosupresores en dermatología. We decided not to include n-grams for Term candidates were word n-grams with Unigrams included in a Spanish stopword list, punctuation marks and digits.Bigrams that include at least one stopword or punctuation marks.Trigrams that include at least two stopwords or punctuation marks or whose last position is a stop word.N-grams that include a country, region or nationality name.N-grams containing dates or years.Finally, all n-grams were normalised to singular nouns, e.g. from “hematomas” to “hematoma”. During this phase, we also extracted the acronyms and their expansions organized by clinical specialty. The new acronym resource is composed of 619 classified acronyms, and the method that we employed to built it is explained in detail in [The first step was to split each text into sentences, the established sentence boundary being “.”, “;”, “?”. “!”. As expected, many n-grams were not terms in a strict sense, such as those beginning or ending with articles and prepositions  have a well-defined application, such as text classification [fication  or queryfication , 49. SinIn this last step, we applied a term weighting strategy that characterizes the n-grams that belong to a clinical specialty and then filters n-grams below a threshold, we refer to them as stop n-grams. The term weighting and filtering strategies consider the following restrictions: Term global measure (TGM) a corpus measure, which quantifies the concentration of a term along with all specialties.Local precision measure (LPM) a specialty-level measure, which represents the specificity of a term for a specialty. Accordingly, high LPM values characterize terms that never or rarely occur in texts belonging to other specialties.Local relevance measure (LRM) it represents the capacity of a term to describe the specialty. Terms with high values are those with high frequency in the specialty, compared to other terms in the specialty, and compared to the frequency in other specialties.The three measures contribute to addressing the “TF = 1 challenge” restriction because the relevance of a term is not computed by text, but by the specialty. In addition, the ability to distinguish the importance of the same term for different specialties and the corpus as a whole deals with the “multi-class texts” restriction.Taking into account the aforementioned restrictions, the weighting strategy considered the following three measures:celoteioma” for oncology), and (2) terms that are not only very frequent in text of the specialty, but also in other texts . Although unspecific they are relevant for the specialty. The differences between these measures contribute to deal with the “multipurpose vocabulary” restriction  infrequent ones with a high predictive power  measure and the algorithm presented in 1.The last step filters the stop n-grams using the thresholdSD and a maximum value lower than a thresholdMAX, it is considered a stop n-gram. We selected the threshold of 47 specialties as it allows us to identify n-grams that are in more than 90% of the available specialties. This, combined with the analysis of importance metrics, allowed us to identify empty n-gram that should not be covered in the resource.The hypothesis behind the algorithm is that an n-gram is irrelevant if its importance in all specialties where it appears is similar and if there is no specialty where its importance is considerably high. The input of the algorithm is the collection of frequent n-grams, i.e., n-grams appearing in more than 47 specialties. Using this collection, the algorithm detects the stop-n-gram candidates by evaluating the standard deviation of its LRM and the maximum value of its LRM across all specialties where the N-gram appears. When an n-gram has a standard deviation lower than a The proposed method was applied to create a set of Spanish terms called SCOVACLIS. For the validation of our initial hypothesis, this resource was used to address a text classification problem.The following sections present the analysis of the method and the results of a text classifier using SCOVACLIS. The text classification experiments were made using the complete SCOVACLIS resource and a reduced version containing only the terms that are also found in SNOMED CT.The first phase consisted of the acquisition of a corpus, consisting of Spanish titles and abstracts belonging to 51 clinical specialties. Figure The consolidation step yielded 635,699 n-grams. The most frequent ones across the specialties are presented in Table As expected, some specialties overlap. Figure In order to test the hypothesis that NLP tasks benefit from more specific terminologies, such as SCOVACLIS, we assessed how much a text classification task can be improved by using the new vocabulary.We propose a multi-label classification. In this classification, the goal was to classify case reports, extracted from PubMed, by one or more clinical specialties to which they belong. To create the gold standard, a PubMed query with publication type “Case report” and language “Spanish” retrieved 54,881 PubMed records with Spanish titles, of which 714 also had a Spanish abstract. Our classification uses both titles and abstracts, counting on average 11.28 and 163.23 tokens, respectively.We used 75% of the case reports for training  and the rest for blind testing . Our available repository contains more information about the distribution of labels for each partition (train and test) created for this evaluation.In addition, taking into account SNOMED CT as a reference terminology in Spanish, we have performed two experiments, (1) using the complete SCOVACLIS and, (2) filtering SCOVACLIS with terms covered by SNOMED CT.Because a PubMed record can be related to one or more clinical specialties, the experiment involved multiple labels per case report (title and abstract). Labels are binary variables that indicate class  membership. This scenario implies greater difficulty due to the computational cost of model generation and querying, as well as the presence of unbalanced labels. In ML, the first step towards training a classifier is text pre-processing, where feature extraction and vectorization take place.Random Forest [m Forest  In our eK-nearest Neighbors [eighbors  The numbDecision Tree [ion Tree  Similar Multilayer Perceptron (MLP) [on (MLP)  a multilWe tested different parameters to adjust the classifiers to the problem n is the number of n-gramss is the specialtyThe results obtained by the different combinations of classifiers and word representation are shown in Table To validate the usefulness of SCOVACLIS, we added features as extra information to each text, using a vector with size 51 according to the number of clinical specialties. The value of each feature is a score calculated following Eq. In the KNN, Decision Tree and MLP classifiers the use of the term set as a feature improved the baseline (TF-IDF). The 10% increase using the MLP method stands out, achieving 64.9% using TF-IDF with the created collection  and performed the same pre-processing as for our term set "" sectionFor this experiment, SCOVACLIS was reduced for each clinical specialty, taking into account only those terms that were included in SNOMED CT. The average number of terms covered by SNOMED CT in all specialties was 28.16%. E.g., dermatology has been reduced from 46,000 terms to around 12,000 and cardiology from 110,000 to around 20,000 terms. With this resource we repeat the classification experiments and applied them to the test data set.We analyzed the characteristics of the terms that were not covered by SNOMED CT in order to recognize possible noise terms in our term set  and with the reduced term set restricted to terms occurring in SNOMED CT (SNOMED CT filter columns). The latter, reduced term set does not improve the original classification. Particularly, when taking into account the F1 measure, we obtained a reduction between 4 and 18 points. This means that the terms included in SCOVACLIS improve the recognition of the specialties, even though they are not canonical or curated terms.Finally, Table Considering that the datasets used for training and testing were not balanced regarding the specialty, this section analyzes the classification error versus the distribution of the class by dividing the F1 results into ranges: 0 to 25%, 25% to 50%, 50% to 75% and 75% and above. 18 specialties with an average of 356 texts for training, obtained an F1 value of less than 25%. nine specialties , obtained an F1 between 25 and 50%, with an average of 2049 texts for training and 688 for testing. Specialties such as pathology and obstetrics and 13 others had an F1 between 50 and 75%, with an average of 2635 training texts. Finally, the specialties that reported the best results  were nine, with oncology and cardiology among them, having on average, 5915 titles/abstracts to train the system. In the first range , there were six specialties with F1 = 0; they contained less than 30 training titles/abstracts and less than seven titles/abstracts for testing, among them were forensic medicine, general practice and allergy, and immunology.This analysis allows the conclusion that, as expected, the more texts the system has for learning, the better it classifies. Our multi-label approach makes the task more problematic as demonstrated by the following misclassifications examples:Example #1.Text: Infiltración pleural en la recaída de un mieloma múltiple.Translation: Pleural infiltration in multiple myeloma relapse.True specialties: cardiology, hematology, medical oncology, pathology and preventive medicine.Predicted specialties: cardiology, hematology, medical oncology and pathology.Example #2.Text: Osteoartropatía hipertrófica en adenocarcinoma de pulmón.Translation: Hypertrophic osteoarthropathy in lung adenocarcinoma.True specialties: medical oncology, pulmonary medicine and rheumatology.Predicted specialties: medical oncology.Example #3.Text: Derivación gástrica en Y de Roux como procedimiento de urgencia para resolver la fuga en un SADI-S.Translation: Roux-en-Y gastric bypass as an emergency procedure for resolving SADI-S leak.True specialties: bariatric medicine and general surgery.Predicted specialties: bariatric medicine, general surgery and gastroenterology.We highlight the difficulty that our classifier has to detect specialties considered transversal  such as pathology, internal medicine or general surgery  is the first accomplishment of this research. The results obtained allow us to recommend this method for obtaining specialized clinical term sets in any language sufficiently represented in PubMed titles and abstracts. Our approach proved useful for recognizing frequent, infrequent, and equally relevant terms that are characteristic of given clinical specialties. The completeness of the term sets obtained by our method is directly related to the volume and richness of the texts obtained for each specialty. It was not surprising that broad, overarching specialties such as general practice or preventive medicine contained less specific terms. and, consequently, underperformed in text classification. Our goal is not to replace existing controlled terminologies, but to support the production of specialized term sets tailored to tasks that require terms with high predictive value, as they occur in clinical or research texts, regardless of naming conventions used for the building of CVs. In contradistinction to these intensively curated resources, the emphasis of our method is on producing term sets in a fully automatic manner, which may include non-standard terms, e.g. with custom abbreviations or frequent spelling variants. This, however, does not exclude at all the potential of our method to provide useful input to terminology developers who maintain and extend clinical terminologies, particularly interface terminologies [The application of this method to a nologies , which fnologies , are in nologies  or use nnologies A resource named SCOVACLIS is the second accomplishment of our research. It allows us to enrich the set of resources available for NLP in Spanish. Creation and validation of SCOVACLIS support the hypothesis that a term set classified by clinical specialties might reduce the level of ambiguity when compared to a specialty-independent, broad-scope vocabulary. Disambiguation, particularly of short forms, is a known bottleneck in clinical text processing.Regarding the validation of SCOVACLIS, its use for improving the features in a multi-class classification approach using a Multilayer Perceptron classifier achieved an increase in 6 percentage points in the F1-measure compared to the baseline. This shows its usefulness to improve contextual knowledge about medical texts and thus better solve NLP problems such as named entity recognition and classification. Also, SCOVACLIS demonstrated an increased text classification performance, compared to the use of curated terms such as the ones included in SNOMED CT, currently the largest source of Spanish clinical terminology. Sotelsek and Villena  obtain sImplementing this method and producing the language resource was not straightforward; were several challenges had to be addressed. Also for the creation of SCOVACLIS, the inevitable restriction to the terminology used in titles and abstracts of research papers is a known limitation, because of its difference from the jargon found in clinical documents, which are known to be hastily written and marred with typos and cryptic short forms. To what extent SCOVACLIS is a useful resource for handling clinical documents still has to be investigated. For future work, we plan to expand our term set and use comprehensive reports.We also had to find criteria to decide which clinical specialties to use; our solution, mainly based on the MeSH occupation hierarchy enriched by other features extracted from PubMed metadata, is more complex than it would have been with clinical texts, whose provenance  would have been trivial to ascertain. In contradistinction, an easily accessible source of biomedical texts is the literature database MEDLINE, with PubMed as a free search engine. From more than 26 million records approx. 2.2 million are about non-English publications, including about 330,000 Spanish entries for which a Spanish title and sometimes a Spanish abstract is available. By using the publication type “case reports” for evaluation, we have extracted a publication genre that is supposed to be closer to clinical language than other, purely scientific papers.Thanks to the existence of freely available query interfaces to PubMed and MeSH, the process of obtaining relevant texts for each specialty was executed. The fact that the universe of publications linked to a medical specialty in MEDLINE is much larger than the set of articles indexed by an occupation-specific MeSH term, led us to enrich the search method by incorporating new elements that allow us to increase the recall of the query.In contrast to related works , the extEven though we used the Spanish titles and abstracts to create the term set, we found a limitation because only 4592 PubMed records were linked to an automatically accessible abstract in Spanish. Thus, most of the texts under scrutiny consisted of titles only. The use of Spanish full texts could be a solution, with about 64,000 Spanish full text sources being freely accessible from PubMed. This, however, would require considerable manual effort.For future work, we plan to explore word embeddings and train some to use them in traditional ML  or neuraThe research hypothesis chosen and tested in this paper was that SCOVACLIS improves classification of medical texts. That SCOVACLIS might also be useful for other NLP tasks is only being discussed, but this could be a subject of future research, given its usefulness for text classification. That our task is fully automated does not exclude human judgements in the evaluation process. MEDLINE is annotated by human experts; our gold standard is largely grounded on these annotations, which we can consider of good quality.The following objectives were pursued with this study: first, to elaborate a method for extracting non-English content from PubMed records; second, to tag these extracts by clinical specialty; and third, to generate characteristic term lists for each clinical specialty.Selection of clinical specialties to be evaluated.Generation of a PubMed extract (titles and abstracts) labeled by clinical specialties.Extraction of word n-grams.Normalization of word n-grams.Generation of metrics that support the selections of the relevant terms in each clinical specialty.Identification of stop n-grams.The resource obtained by applying this method to Spanish titles and abstracts, named SCOVACLIS, was evaluated in a multi-label classification task. The results have shown that our resource improved the baseline (without SCOVACLIS). We obtained an F-measure of 65.2% using an MLP network, 77.5% in precision and 57.7% in recall using TF-IDF representation, and SCOVACLIS without stop n-grams as features.The method for the automatic extraction of medical terms involves the following steps: Finally, the creation and validation of SCOVACLIS support the hypothesis that specific term sets classified by clinical specialty might reduce the level of ambiguity when compared to a specialty-independent and broad-scope vocabulary.