In many countries inability to work fulltime is recognized as an important concept in work disability assessments. However, consensus is lacking regarding the concept and how it should be assessed. This study seeks to conceptualize and operationalize the concept of inability to work fulltime, and includes perspectives of both patients and physicians. Research questions involve identifying: 1. key elements, 2. measurable indicators, and 3. valid methods for assessing indicators of inability to work fulltime.We used a qualitative study with a thematic content analysis design to conceptualize inability to work fulltime, based on nineteen semi-structured interviews conducted among insurance and occupational health physicians, and representatives of patient organizations.Inability to work fulltime is conceptualized as a complex concept which is strongly individually determined and variable due to time and underlying disease. Key dimensions of inability to work fulltime included besides the disease itself, also personal factors like psychological and lifestyle factors, as well as environmental factors related to the work situation and social context. Fatigue, cognitive impairments, and restrictions in functioning in- and outside work were reported as important measurable indicators. A combined use of self-assessment, assessment interviews, and testing, and assessment in the actual (work) setting was identified for assessing these indicators.Taking into account the complex and variable nature of inability to work fulltime, we found it advisable to use multiple methods and multiple time points for the assessment. Results of this study provide starting points for further research on the operationalization of inability to work fulltime in a work disability context. As being able to work is vital for a person’s economic self-sufficiency and social standing, valid assessment is of great importance.Social security systems generally distinguish two main aims of work disability assessment: to decide about eligibility for disability benefits, and to determine what people are still able to do regarding work . IncludeIn many European countries, inability to work fulltime is recognized as an important concept in work disability assessments ; the conThe few existing studies that assess the hours a person is able to work demonstrate confusion regarding the meaning of the concept inability to work fulltime , 3. FirsConceptualization involves formulation of clear and concise definitions: identifying the key elements, using characteristics (non-measurable key elements) and dimensions (measurable key elements). Conceptualization is followed by operationalization: making an abstract concept measurable by describing its dimensions and translating these into measurable indicators . EffectiThis study seeks insight regarding conceptualization and operationalization of the concept of inability to work fulltime, based, among other things, on the perspectives of both patients and physicians. To assess the concept effectively, we also want to explore its dimensions and indicators. Our specific research questions are: 1) What are the key elements (characteristics and dimensions) of inability to work fulltime?; 2) What are measurable indicators of inability to work fulltime?; and 3) Which methods can be used to assess the measurable indicators of inability to work fulltime?For our study, we used qualitative interviews to explore the concept of inability to work fulltime. Qualitative research is useful for understanding complex issues, explaining people’s beliefs and behaviours, and identifying social or cultural norms . To evalDutch law required no ethical approval for this study, as participants were not subject to any intervention. All participants provided informed consent to record the interviews and publish the results, given that data were anonymized and untraceable to individuals. Participation in the study was voluntary, and participants received no incentive for participation.We explored the concept inability to work fulltime from the perspectives of both the patient and the physician in order to triangulate points of view from these two main stakeholders.We invited physicians in staff and/or management positions in insurance and occupational medicine and in both public and private disability insurance, preferably with practical experience and with adequate knowledge of work disability assessment at scientific or staff levels. For the patients’ perspective, we invited representatives, expert staff members of patient organizations in the Netherlands, to participate. Patient organizations provide information, offer fellow sufferers contact, promote interests, organize activities, and support groups of specific patients not only with healthcare issues but also regarding social and employment participation. A patient organization is often established for and by patients. We purposively sampled patient representatives to include the major disease groups related to work disability , and to examine their experiences with the (in)ability to work fulltime. The researchers invited physicians from their own professional networks, and contacted most patient representatives through the websites of their organizations, or their professional networks. The authors approached participants by email and telephone to describe their own role, as well as the aim and context of the study.Between January and September of 2014, we conducted semi-structured interviews using open-ended questions. We developed an interview guide with topics and open-ended questions to aid the interviewers and to ensure comparability of the interviews, thereby increasing reliability. We tested this script with three insurance physicians, recruited from the researcher’s own network. Based on these try-out interviews the interview guide was fine-tuned, using more open questions. We chose to interview physicians and patient representatives to acquire data on (the assessment of) inability to work fulltime from the perspective of the key participants in the disability assessment interview.more information about the research team members can be found under Acknowledgements]); one interview was conducted by the first author only (HJB). We conducted all interviews in the participants’ first language (Dutch), during single sessions of 45–90 min; all were audio-recorded. We made no additional field notes. We interviewed most participants at their own preferred locations, and two by telephone; no other persons were present during the interviews. We transcribed all interviews verbatim. We did not present transcriptions to the participants for their comments, but presented and discussed our interpretations of the data at professional meetings with researchers, professionals, and policymakers in the field of work and health.The final interview guide addressed the following major topics: 1) the concept of inability to work fulltime and its characteristics; 2) dimensions of inability to work fulltime; 3) indicators for measuring the dimensions of inability to work fulltime (signs and symptoms of the concept and its dimensions); and 4) methods to assess indicators of inability to work fulltime. Subtopics included: what is ‘normal ability to work fulltime’, or the maximum number of hours a person can work; disease specific aspects related to variability of inability to work fulltime; the best method to assess indicators of inability to work fulltime; and experience with assessing inability to work fulltime. To explore these topics more deeply, we asked further clarifying questions. Of the 19 interviews, 18 were conducted by two interviewers , translated into English by a professional translator, and discussed with all co-authors. To indicate the diversity of opinions while maintaining anonymity, we indicate quotes from physicians with Ph1-Ph10, and from patient representatives with Pa1-Pa9.In the final iteration, we formed a conceptualization based on emerging themes describing the key elements. We used these key elements to operationalize the concept into relevant characteristics, dimensions and measurable indicators, and inventory methods for assessing these indicators. Although the interview guide contained no questions regarding the International Classification of Functioning, Disability and Health (ICF) , we wereWe initially invited 33 persons (13 physicians and 20 patient representatives) for interviews, 19 of whom (ten physicians and nine representatives of patient organizations) agreed to participate. Reasons for refraining from participation varied: lack of time, illness, insufficient expertise, or the topic or interview did not fit with the scope of the organization.n = 3) Pa1–3, diseases of the nervous system (n = 3) Pa4–6, genitourinary system disorders (n = 1) Pa7, neoplasms (n = 1) Pa8, and diseases of the respiratory system (n = 1) Pa9). All subjects had received higher education, most at university level; six were female. All worked as project manager, (senior) staff member, or advisor.In our final group, seven out of ten physicians were insurance physicians: four working in public disability insurance (Ph1–4), and three working in private disability insurance (Ph5–7). Three participants were occupational health physicians (Ph8–10). Nine physicians were male, and five had obtained a PhD-degree. The nine staff members from patient organizations represented patients with five disabling chronic diseases , the measurable indicators, and the related assessment methods was intertwined. An overview of the terminology and main findings is presented in Table “What do you consider a normal work-time capacity?”: “that, of course, varies from person to person” Pa8). A physician stated: “the work capacity, that is different for each person” (Ph7). Additionally, two aspects were described characterizing the variable nature of inability to work fulltime: variability due to time, and variability due to the underlying disease.Most participants found inability to work fulltime a complex concept to operationalize. It describes the inability of a person to work normal working hours, i.e. not able to work a normal number of hours per day and per week. Important characteristics of inability to work fulltime are that it is strongly individually determined and is variable. One patient representative stated when asked; We are not machines. We are influenced by all sorts of things happening in and outside ourselves over time. That varies all the time” (Ph3). Another physician stated: “When you’re talking about work ability in terms of a social norm, I think it varies over time. Nowadays we expect other things from people than twenty years ago” (Ph1).Inability to work fulltime varies over time due to many different factors. As one physician stated: ““The physical capacities may decline somewhat over the years, but you can make up for that with things like increased skills” (Ph7).Both physicians and patient representatives mentioned that with age, people have a reduced capacity to bear physical and cognitive strain, need more recovery time, and are less resilient. However, physicians also described a learning curve over time, involving the development of more (cognitive) skills that may compensate for this reduced physical capacity; as one physician stated: Even some people with depression are able to work” (Ph1), and “We all know that a well-known feature of all kinds of depressive disorders is that they fluctuate” (Ph3).Participants mentioned that variation in severity and complaints, the effect of treatment and training, and personal and external factors may affect a person’s ability to work fulltime. The type of disease was often mentioned as a variable factor related to, and a potential indicator of, the impaired ability to perform working activities; examples were severe heart failure and chronic renal insufficiency. However, they stressed that not only having the disease (the diagnosis) itself causes inability to work fulltime, but also the course of the disease. Physicians remarked, ““Well, work ability varies with the clinical picture, the health condition, whether the condition is active, and whether there are treatment options now or in the future” (Ph2).Additionally, most participants mentioned treatment and rehabilitation as factors influencing the number of hours a person can work. For example, cancer treatments and time-consuming kidney dialyses were mentioned as significant barriers to being able to work fulltime. However, cancer rehabilitation, sports, cognitive training, and stepwise functional recovery were mentioned as factors that positively influence inability to work fulltime, regardless of the person’s diagnosis. A physician stated: “Some people just get hung up on it; others don’t” (Ph3). One patient representative stated: “Some people just want to achieve a higher ability to work because it has to do with certain personal life goals” (Pa9).Besides the type of disease, several personal factors were mentioned as key dimensions of the inability to work fulltime. Physicians reported further psychological factors, such as a person’s (in)ability to cope, as well as motivations and orientation in life, as important aspects that influence the number of hours a person can work. Patient representatives mentioned an improved lifestyle , positive orientation and goals in life, the choice to work self-employed, having self-confidence, and coping with the disease to be of influence. One physician said: The moment you create more possibilities at work, people have the ability to make a positive contribution to work, even at higher ages” (Ph9). A patient representative said, “All circumstances at work, and whether or not you are satisfied with them, play a very important role in your work capacity” (Pa2).As environmental factors, physicians mentioned work-related factors  and workplace factors . Patient representatives added organizational policies and practices, social support, job control and job fit, conflicts at work, discrimination, and re-organization as factors associated with the ability to work fulltime. One physician said, ““When you have big problems in your private life, you can be physically able to work, but your true ability to work and your productivity will be lower as long as these issues are not resolved” (Ph9). A patient representative said, “When you have a good partner, good support and feel well, you are better able to cope with your limitations” (Pa6).Regarding social factors, we found that workers’ social situations can impact the number of hours they are able to work. A person’s household, family obligations, family concerns, problems and worries, may negatively influence the ability to work a certain number of hours per day or per week. However, family support can also have a positive effect. A physician said, “What is expected of a worker is based on legal or social norms. Apparently, a Dutch fulltime employee is legally required to work 40 or 38 hours, depending on the labor agreement, or fewer hours, depending on the employment contract. But that doesn’t say anything about his physical ability” (Ph5). A patient representative said, “I think that most people are able to work between 30 to 40/50 hours (per week), but it strongly depends on where you come from and on your upbringing” (Pa3). Participants generally agreed that every person has his or her own maximum of hours that he/she can work, and stated that it is impossible to prescribe a universal maximum of working hours. A patient representative stated, “I think the maximum amount is very personal and very much dependent on the sort of work you do. I don’t think there is an upper limit that applies to everyone” (Pa8). Physicians stated that the maximal number of hours a person can work per day or per week may differ from person to person, ranging from 9 to 12 h per day and from 55 to 80 h per week. According to the physicians, the upper limit is influenced not only by health status, but also by personal factors , and environmental factors . Frequently exceeding one’s maximum may lead to long-term health complaints and negative health effects, indicating a need to recover from physical and mental work efforts for a shorter or longer period of time. A physician stated, “Research shows that people make more mistakes, get tired and have more problems concentrating if they work longer than nine consecutive hours without a break” (Ph9). A patient representative said, “In earlier days, and nowadays in some countries, people worked from sunrise to sunset, and then went to sleep. That’s exhausting, and that’s why these people didn’t get very old” (Pa3).Further, most participants stated that societal norms strongly influence what is generally considered to be normal. Both physicians and patient representatives considered fulltime working as normal, but the number of hours per day and per week may differ, depending on societal norms. These norms can be based on legal and collective arrangements between employers and employees regarding working conditions, on policies within companies, and on insights within social groups. A physician said, slow recovery”, “specific disease-related complaints like pain and dyspnea”) while those representing patients with mental disease mentioned more cognitive indicators .We found three relevant measurable indicators to assess inability to work fulltime: fatigue, cognitive impairments, and problems in functioning in- and outside work. Patient representatives of patients with somatic diseases mentioned more physical indicators , and “run into all kinds of barriers” . Physicians stated that these people “feel unable to work the whole day” (Ph8), that “they can’t accomplish anything anymore after six hours of work” (Ph8).Fatigue was reported as an important indicator of inability to work fulltime. Patient representatives stated that people with inability to work fulltime “can’t cope any longer” (with a full day’s work) (Ph5), that they “need more time to understand things” (Ph2). Participants also mentioned that people with inability to work fulltime have problems with cognitive and complex tasks, stating that they “forget” (Pa7), “make mistakes” , “have no overview” , and “have fewer problem-solving abilities” (Pa5). Some also mentioned emotional complaints as indicators of inability to work fulltime, such as “irritability” , “less able to cope with conflicts” (Pa4), and “mental decompensation” (Pa5).Physicians stated that people with inability to work fulltime Most participants reported that people who cannot work fulltime have problems with functioning both in- and outside work. They emphasized the importance of having sufficient time to recover from work, and balancing work with other activities like household tasks, self-care, and social activities.“doing less” (Ph6), “needing a power nap” (Ph9), “being unable to do anything in the evening hours after work” (Ph3), “not being able to get out of bed” (Ph7), “going to sleep during the day” , “[making] mistakes in their work” (Ph9), “function[ing] less well at work when they continue to work longer” (Ph2), “[being unable to] visit friends anymore in the evening” (Pa7), and “not [being] able to go out anymore or do sports” (Pa4).For example It is relatively easy to determine that someone is unable to work fulltime, but when it comes to assessing the level of inability to work fulltime we are just swimming” (Ph4).Quantifying the number of hours per day a person can work is seen as an enormous challenge. As one physician indicated, “After we explored how best to assess the indicators of inability to work fulltime four methods emerged: self-assessment, assessment interviews, functional testing , psychological tests and ergometry ), and assessment in the actual work setting. Although there was no consensus about a single best method, most participants found it insufficient to use only one instrument.people with certain disorders, like depression, may have trouble realizing their own limitations” (Pa1). Physicians also stated that a client’s own estimation of functional impairments, activity limitations, and participation restrictions may need to be complemented with additional information, such as that provided by a semi-structured assessment interview.Self-assessment methods alone were not regarded as a suitable measure. Patient representatives pointed out that “the simple conversation at the social security institute doesn’t work”. They declared that the assessment interview should also include “examples of functioning and daily activities, information from treating physicians, and checking for inconsistencies” (Ph5), as well as “recovery after exertion, the personality of the client, and the psychosocial situation” (Pa7), and could be supplemented with “speaking with people next to clients, like significant others, employers or mentors” (Pa3), and gathering “information about what happened before, in the first two years of sick leave” (Pa4).Although most physicians considered an assessment interview to be an important method, especially in combination with other methods, patient representatives found such interviews invalid. They considered the method too simplistic; as one patient representative (Pa3) stated, “Testing with neuropsychological assessment and ergometry (exertion-tests and VO2max-determination) contributes to the assessment of inability to work fulltime, but is not the final answer” (Ph6); this applies especially to certain disorders or conditions like traumatic brain injury, and heart and lung diseases.Most participants (both physicians and patient representatives) mentioned the value of clinical tests, separately or in combination with other methods, as methods for assessing indicators of inability to work fulltime, such as fatigue and cognitive problems, and not just inability to work fulltime in itself. As a physician explained, “Observe if someone makes mistakes or takes rest during trial placement” (Pa5). Participants indicated a need for repeated observations and long-term follow-up, suggesting periods from six weeks to three months.Both physicians and patient representatives regarded trial placements and observation at work as appropriate ways to discover the extent of a person’s capacity to work. This trial and error setting makes it possible to test and observe indicators of inability to work fulltime. As a patient representative stated, “In this study we aimed to conceptualize and operationalize the concept inability to work fulltime by interviewing physicians and patient representatives and analyzing their answers. Our results show that inability to work fulltime describes the inability to work normal working hours and is considered a complex concept to operationalize, as it is strongly individually determined and variable. The underlying disease and changes in the situation over time make the concept variable. Moreover, we found that key dimensions of inability to work fulltime included not only the disease itself, but also personal factors like lifestyle and psychological components, as well as environmental factors related to the work situation and conceptions regarding what constitutes a ‘normal’ number of working hours. Fatigue, cognitive impairments, and restrictions in functioning in- and outside work were reported as important measurable indicators of inability to work fulltime. To assess this inability, participants regarded assessment interviews, testing, and evaluation in the actual work setting as the most suitable methods for measuring indicators, and expressed a preference for their combined use. They also mentioned the importance of repeated assessment, given the longitudinal and variable nature of inability to work fulltime. Self-assessment methods alone were not considered suitable. In all, the results of this study provide insight into the key elements (characteristics and dimensions) of inability to work fulltime, some important measurable indicators, and methods that can be used for assessment. Our results thus contribute to more evidence-based work disability assessments.Our findings indicate that the inability of workers to work fulltime, due to disabling chronic health conditions and/or other causes, should be treated as a complex set of personal and environmental factors, and is variable. This aligns with the conclusions of other research in this area, that the inability to work fulltime has a complex character. This underlines the complexities of work disability assessments in general , 14. MeaOperationalization of the concept inability to work fulltime revealed a broad perspective involving the disease, personal factors, and environmental factors, and emphasized the importance of the context of the individual. In this context, his/her career is significantly influenced by societal norms, cultural aspects, and policies regarding accepted norms for working fulltime , 17. AltThe reported measurable indicators of inability to work fulltime can be used as signals to assess the number of hours a person is able to work. They are crucial starting points to help assessors to unravel the question of reduced ability to work fulltime. However, some indicators are not necessarily only preconditions of an inability to work fulltime, as they can also be described as generic and frequently occurring expressions of disease. For example, although fatigue can be caused by a disease or treatment, and be a reason to stop working or reduce tasks, it can also be a response to working too many hours or having too great a workload. Our results are in line with the Dutch guideline  which meSeveral validated self-report instruments are available to measure the reported indicators, such as questionnaires on fatigue or energy deficits , 21, paiFurther research is needed to evaluate the measurement properties of the different assessment methods and their combinations.To our knowledge, this is the first study to follow a multi-perspective approach to conceptualize and operationalize the concept inability to work fulltime as part of disability assessment. It is promising both physicians and patient representatives made similar observations. In addition, the study included a wide variety of physicians and patient representatives, thereby providing broader insights into the characteristics, dimensions, indicators and methods of assessing inability to work fulltime.This study also has some limitations. First of all, the study included only representatives of patient organizations. Although some of them are patients themselves, it is their job to lobby for the interests of their organizations; including a wider variety of patients might have produced different data. Further, the physicians were more often male, and representatives of patient organizations were more often female, but we expect that this did not influence our study results, as congruent findings were found from both perspectives. A second limitation may be some educational bias, as our participants had all received higher education; we may thus have missed relevant responses from people with less education regarding inability to work fulltime. This may reduce the generalizability of our study findings. Finally, our interviews took place in 2014; nevertheless, we are convinced that our data are still valid, as the practice of assessment of inability to work fulltime has not changed since that time.Although our exploratory work cannot deliver a totally clear definition and operationalization of inability to work fulltime, it clearly indicates areas worthy of future research and practice. The complex nature of inability to work fulltime requires comprehensive assessment methods, combining subjective and objective measures, to allow for a grasp of the multiple indicators related to the concept. This conclusion corresponds with findings in previous research on measuring complex concepts , 13, 14,Inability to work fulltime is considered a complex concept to operationalize. It is strongly individually determined and variable, and depends not only on disease and personal factors, but also on environmental factors. We found three important measurable indicators: fatigue, cognitive impairments, and restrictions in functioning in- and outside work. To assess inability to work fulltime, participants mentioned assessment interviews, testing, and assessment in the actual work setting as the most suitable methods, and expressed a preference for the use of combined methods; they regarded self-assessment methods alone as inadequate. Taking into account the complexity of inability to work fulltime, and its possible variation, we would thus recommend using multiple methods, and at multiple time points. The results of this study provide starting points for further research on the operationalization of inability to work fulltime in the work disability context, and contribute to more credible work disability assessments.


Management of brain metastases is challenging, both because of the historically guarded prognosis and evolving, more efficacious treatment paradigms for metastatic cancer. This perspective addresses several of the important difficult questions that practitioners treating patients with brain tumors face in the clinic. Successfully answering these questions requires knowledge of the clinical evidence, thoughtful discussion of the patient’s goals of care and collaboration in a multi-disciplinary setting. As the articles in this special issue illustrate, the management of brain metastases has changed and continues to evolve. Advances in radiation therapy, surgery and, particularly, systemic treatment of metastatic cancer have improved prognosis and increased longevity, making the preservation of neurocognition and quality of life all the more important in patients with brain metastases. The choice of treatment for brain metastases – including early and timely access to palliative care – has become more complex and complicated. At the same time, the consequences of making the optimum management choice carry higher stakes for both the patient and practitioner. While there is no single correct approach, clearly the “best” decisions will come through attentiveness to the patient’s goals of care and the input of multiple disciplines.In this article, we share our perspective on some of the most common and important questions we encounter in the clinical management of brain metastases. The astute reader will notice that many of the “answers” to these questions, raise more questions than provide answers, and that there is no “magic eight ball” that provides a simple answer. However, a collegial effort on the part of the “village” - medical oncologists, radiation oncologists, surgeons, palliative care specialists, navigators and nurses - centered on addressing the patient’s needs and based on evidence, will provide the best care and superior outcome for the patient presenting with brain metastases.Patients often present with large brain metastases that are producing or at impending risk of causing symptomatic mass effect on brain parenchyma, critical adjacent organs and the ventricular system. These patients are typically considered for surgical resection – particularly in the case of one or two brain lesions – for rapid relief and/or prevention of mass effect and obstructive hydrocephalus. Radiation therapy is usually administered in combination following surgical resection of a brain metastasis, as either whole-brain radiation therapy  (WBRT) oClinicalTrials.gov Identifier: NCT04114981.)However, even for modest-sized brain metastases, the resection cavity and resulting target volume for irradiation is often in excess of 3 cm , requiriPre-operative SRS is a potentially attractive alternative to post-operative SRS, as the target in the pre-operative setting is smaller and more regular with a more competent blood supply, presumably providing better oxygenation and, thus, increased radiosensitivity , 8. MoreIf the patient is not surgical candidate, the treatment of large brain metastases with radiation therapy alone is an option. The need to balance toxicity with efficacy of treatment suggests that these patients may be best served by HF-SRS, as discussed above, rather than WBRT with its increased risk of neurocognitive deficits and prolonged recovery time or single-fraction SRS with greater risk of adverse-radiation effects at efficacious doses. Omitting resection in surgical candidates is more contentious. Some retrospective studies have shown substantially poorer local control for lesions exceeding 2cm diameter treated with single-fraction radiosurgery alone versus resection and radiosurgery , likely which should include appropriate targeted and immunotherapy agents – the optimal answer to the above question can best be achieved in a multi-disciplinary setting. Obviously, one needs to consider the patient’s suitability for surgery and radiosurgery, the size, location, aggregate volume and number of lesions and the patient’s performance status, disease burden and goals of care. In addition, the timing of and interaction with systemic treatments must be considered, as well as the appropriateness of any intervention in patients with poor prognosis and performance status  and multiple studies have shown that WBRT causes significant neurocognitive deterioration versus SRS alone –18. Consclinical appropriateness of doing so. By intent, SRS delivers a minimal dose of ionizing radiation to non-target tissue, permitting untreated sub-clinical metastases to develop into visible lesions at later date. Consequently, multiple studies show that the incidence of development of new brain metastases is far higher without than with WBRT (However, the technical capability to radiosurgerize 30 brain lesions should not be equated with the ith WBRT , 24, 25.ith WBRT ]. Finallif the patient has prospects of benefitting from treatment. As the QUARTZ study showed (In response to the above question, when the patient has a high density of brain metastases, WBRT should be considered and may be the most appropriate option y showed , patienty showed , 28. 518Given that memantine alone offers only partial neuroprotection and that substantial changes in non-hippocampal areas of the brain are observed post HA-WBRT , there iThe above discussion reflects the Author’s radiocentric experience in treating brain metastases. However, the prospect of deferring and potentially completely avoiding any radiotherapy to brain metastases is being entertained, as discussed elsewhere in this issue. For example, in non-small cell lung cancer metastatic to the brain, targeted agents with improved blood-brain barrier penetration, such as osimertinib, can effectively treat small brain metastases without brain irradiation , 30. HowAs I have gotten older, this question has changed from “… if I were your mother [or father]?” to “… if I were your sister [or brother]?” Many of my colleagues would say it be more appropriate to ask “… if I were your daughter [or son]?” I now recognize that this question opens the door to an opportunity to frame the patient’s goals of care and to engage in a meaningful dialogue with the patient and their family. In a busy clinic, one’s inclination is to give the rote answer, “I treat everyone equally. I am not your relative and it would not be appropriate for me to answer that question”, moving on to a discussion of risks, benefits, side effects and logistics. However, by taking just a few more minutes at this critical point, a provider can truly help the patient chose an option best aligned with their goals of care.and I understood how these options fit with their goals”. Then, either I or the patient/family member will briefly recap the patient’s goals and discuss how the management options fit with those goals. Throughout this dialogue, it is essential to repeat, acknowledge, clarify and rephrase what the patient is telling you, making liberal use of phrases, such as, “Let me make sure I’ve got this right. You want to…”If I have developed rapport with the patient, my first response is often, “well you don’t know how I feel about my mother [or father], so you may want to be careful about any answer I would give you”. This comment is surprisingly well received in most cases and is far more effective than a brief lecture on shared decision-making. Then, I typically follow-up with, “I would start by making sure I explained the different treatments to them [my parent] – as I’ve done with you – and by making sure that they Effective multi-disciplinary management of these patients requires that all team members share the summary of these discussions with one another, with a low threshold for referral to another specialty, as needed. In particular, one must be attentive to a need for improved symptom management and home health care, areas where a Palliative Care provider can offer exceptional support to the patient and their family.Yes. Safe and effective SRS of brain metastases requires more than a radiosurgery capable piece of equipment. Paraphrasing the guidelines for radiosurgery proposed by Barnett et al. , the key• A multidisciplinary team consisting of a neurosurgeon, radiation oncologist and radiation physicist, all trained in radiosurgery, in general, and the specific equipment, as well as a team of dedicated radiation therapists• Sophisticated treatment planning based on high-resolution, high-fidelity imaging that yields highly conformal, precise and accurate dose delivery to the target with minimal irradiation of normal tissues• A linear accelerator, particle therapy unit or radioactive isotope device, capable of delivering photon or particle radiation to a remote target with better than 1 mm accuracy and precision• A combination of patient immobilization and on-machine image guidance that ensures that the target is localized with sub-mm/sub-degree accuracy in translational/rotational accuracy• Robust, written and rigorous quality assurance procedures for every element of the process that ensures that every element of the system is correct during each and every procedureIf these requirements cannot be met locally, an alternative approach should be considered, including referral to a radiosurgery center, use of conventional radiotherapy and/or systemic treatment with proven efficacy in treating brain metastases, as appropriate.Thoughtfully addressing the above questions with patients and their families in a multidisciplinary setting is a critical element in the treatment of brain metastases. Formulating and communicating evidence-based, specialty-agnostic recommendations with careful attention to the patient’s needs and goals of care provides the patient with the basis to make optimal, personalized decisions on their care.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.The author confirms being the sole contributor of this work and has approved it for publication.JK has research funding from Varian Medical Systems and the BioMimetix SBIR, receives consultant fees from Monteris and is the co-owner of ClearSight RT, LLC.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


There has been growing concern over the use of electronic cigarettes (e-cigarettes) in recent years. Although advocated as an aid to smoking cessation, there is increasing evidence of harm not just to the respiratory system, but to all other organs in the body. To give a clearer picture on how e‑cigarettes can affect our health, we gathered an overview of the literature on the various health effects of e‑cigarettes and categorized them into how they specifically affect organ systems.E‑cigarette exposure has produced a range of stress and inflammatory reactions in the pulmonary system, including shortness of breath, coughing, wheezing, bronchial and pulmonary irritations, and impaired pulmonary function. In the oral and gastrointestinal system, gingival inflammation, sore throat, nausea, vomiting, and diarrhea have been reported. Increased tachycardia and blood pressure were reported reactions in the cardiovascular system. In the neurological system headaches, irritability, anxiety, dependence and insomnia were observed. Other effects included ocular irritation, contact dermatitis, acute renal insufficiency, toxicity and potential carcinogenicity. Nevertheless, studies have found improvements in time-based memory and nicotine withdrawal associated with the cessation of conventional cigarette smoking and switching to e‑cigarette use. Also, toxic and carcinogenic metabolites were reportedly lower in e‑cigarette smokers than in conventional cigarette smokers.A growing number of studies are showing the adverse effects caused by e‑cigarettes on all human organ systems. Further research on the chemical components, the diverse flavors, and the long-term effects on active and passive users are needed to clarify the implications of e‑cigarette use on individual and public health. Electronic nicotine delivery systems, known commonly as electronic cigarettes or e‑cigarettes, are hand-held battery-powered devices simulating the structural, behavioral and arguably physiological aspects of traditional smoking . In eachWith the evolution of e‑cigarettes into the third and fourth generations as well as the growing prevalence of their use, there has understandably been increasing concern on their health effects –6. This According to Public Health England, e‑cigarettes were reported to be 95% less hazardous than tobacco cigarettes . ApparenE‑cigarettes were commercially available in Europe and in the USA as of 2006, with reported use increasing dramatically over recent years; nevertheless, global use seems to remain low . E‑cigarThe use of e‑cigarettes is also increasing among adults . PrevaleTo give a clearer picture on how e‑cigarettes can affect our health, we gathered an overview of growing evidence in the literature on the various health effects of e‑cigarettes and categorized them into how they specifically affect organ systems. PubMed and Google Scholar were selected as primary databases, from which the search terms electronic cigarettes, electronic nicotine delivery systems, health effects, review and public health were entered. Searches were limited to literature in the English language and those that were published from January 2015 to November 2019.Table E‑cigarette exposure produces a range of stress and inflammatory reactions in the areas of the body in which it comes in first line of contact: the mouth, the nasal passage, the trachea, the bronchial system, and the lungs. Exposure to the main component of e‑cigarette liquid, propylene glycol, has incited airway irritation (similar to ocular irritation) airway obstruction and an increased severity of dyspnea among individuals who did not previously have the condition , 26. DepE‑cigarette use has also been reported to potentially induce chronic obstructive pulmonary disease . EffectsThere are studies on the oral health effects of e‑cigarettes suggesting that e‑cigarette aerosols can cause harm to oral health by inducing gingival inflammation: however, there is limited evidence to show that switching from conventional cigarettes to e‑cigarettes improves periodontal disease in smokers .The most common gastrointestinal symptoms associated with vaping were epigastric pain, nausea and vomiting, followed by diarrhea and hemorrhage, which Gaur et al. attributed to the trace metals copper and chromium in the aerosol if exposed to high levels , 27. FurAn increase in heart rate and blood pressure due to e‑cigarette use has been reported , 20; howStudies have found improvements in time-based memory and nicotine withdrawal associated with the cessation of conventional cigarette smoking and switching to e‑cigarette use . It was Although toxic and carcinogenic metabolites were reportedly lower in e‑cigarette smokers than in conventional cigarette smokers, a few e‑cigarette users were found to have higher than expected levels of urinary metabolites of lung carcinogen and tobacco-specific nitrosamine . While tThere have been cases of nicotine poisoning in children and an infant through accidental ingestion of the e‑cigarette refill fluids. These children experienced sudden onsets of vomiting, and in one case tachycardia, grunting respiration and truncal ataxia were reported . All patFrom the gathered evidence, e‑cigarette exposure has produced a range of adverse reactions affecting all of the major organ systems. Most of them have been associated with the respiratory system, where a range of adverse effects from throat and mouth irritations to stress and inflammatory reactions, severe respiratory obstruction and even death has occurred. In the gastrointestinal system, e‑cigarette aerosols have been found to cause gingival inflammation and periodontal diseases, nausea, vomiting, diarrhea and abdominal pain. In the cardiovascular system, increased heart rate and blood pressure has been frequently reported, although more serious cardiovascular conditions were rare. E‑cigarette use has also been found to create headaches, jitteriness, anxiety and irritability, and the nicotine variants may have long-term negative effects on memory function. E‑cigarette liquids and aerosols have been found to be skin irritants, have toxic components that are poisonous when accidentally ingested, or may have DNA damaging and carcinogenic effects in concentrated doses.Despite the growing evidence there are limitations to consider. Firstly, much of the data come from case reports or cases series. Although some of the known toxic effects of the constituents found in e‑cigarettes were evident in biological models, they may not have the exact effects on humans . In someIn the European Union (EU), there have been substantial differences between the laws, regulations and administrative provisions on the manufacture, presentation and sale of e‑cigarettes in member countries since 2014. Furthermore, there is no EU-wide regulatory framework guaranteeing their safety and quality . The recLikewise, the FDA  has requE‑cigarettes are similarly regulated in 68 countries using existing tobacco legislation, new policies or amendments to legislations. But this could be challenging, as e‑cigarette manufacturers are using sales and marketing tactics along with the far-reaching potential of the Internet to stay ahead of these regulations . On the While e‑cigarettes have been reported to have the potential to reduce harm caused by conventional cigarettes with users being mainly cigarette smokers wanting to quit, a recent meta-analysis concluded that e‑cigarettes reduced the probability of quitting , 44, 45.Similarly, it is problematic that the popularity of e‑cigarettes among youth and adult non-smokers is increasing through aggressive marketing, attractive flavorings and perceptions of reduced risk. Since they have been reported to serve as a gateway to conventional cigarette smoking, e‑cigarettes can hardly be a tool to improve public health value , 45.According to a report from the European Regulatory Science on Tobacco (EUREST) consortium, the wide variety of chemical components and flavor additives warrant further investigation . It asseBased on the existing evidence, no firm conclusion as yet can be drawn regarding the safety of electronic cigarette (e‑cigarette) use, but a growing number of studies are showing the adverse effects it causes in the respiratory system, the gastrointestinal system, the cardiovascular system, the neurological and cognitive system, the urogenital system, the hematopoietic system, and on the skin. As described in the background, e‑cigarettes have been improving smoking cessation. Nonetheless the evidence is scarce, and as the health effects of continued e‑cigarette use are unknown and underresearched, e‑cigarettes should only be used under close medical supervision. Yet, as e‑cigarettes are relatively novel, sensational and freely available on the Internet, the likelihood of young people starting with them and then moving on to combustible cigarettes is high. E‑cigarettes are regulated to various extents around the world, but their safety and quality is not guaranteed. Given the gathered evidence, the use of e‑cigarettes as a public health tool is questionable.


Sisom OI paper prototype was launched by seeking the perspectives of end users, including children with OI and their clinicians.Children with osteogenesis imperfecta (OI) experience a diversity of symptoms that expose them to difficult physical, mental, and social challenges. Sisom  is an interactive assessment and communication tool designed to help children aged 6-12 years with chronic conditions express their symptoms. Recently, the co-design of the Sisom OI paper prototype.The aim of this study is to describe the experiences that children with OI were prompted to share with researchers during the co-design of the Sisom OI paper prototype. The themes and subthemes identified from the data sources were generated using qualitative description.A secondary analysis of qualitative data was conducted at a university-affiliated, pediatric, orthopedic hospital. The data sources consisted of interview transcripts, drawings, field notes, and observations derived from interviewing 12 children with OI who participated in the co-design of the Relating to Others, described the balance between feeling different versus feeling similar to other children. The subthemes were Common OI Experience, Feeling Different, and Feeling Just Like Others. The second, Relating to Their Condition, described children’s positive and negative interactions with their own condition and health care. The subthemes were Understanding Their Condition, Special Relationship with the Hospital, and Difficult Treatments and Procedures. The third, Reflecting on Capabilities, described children’s recognition of their strengths and limitations. The subthemes were Perceiving Limitations, Overcoming Isolation, and Celebrating Strengths.Three themes were identified. The first, This co-design process provided children with OI the space to not only contribute to the development of the end product but also eloquently describe their experiences. These findings, based on the descriptions given by the children themselves, offer us a unique understanding of what it means to grow up with OI. Osteogenesis imperfecta (OI), otherwise known as brittle bones disease, is the most common inherited chronic bone disorder -4. The pConvention on the Rights of the Child, which states that every child has the right to express themselves and be heard by others in matters that affect their well-being . Those who were more expert related their own experience to how others might feel:One child advocated for the creation of Sometimes people are, are so like, you don’t know what you want, but that happens to me sometimes and sometimes people will cry because of that. Like me.P4, 8 years old, type IV OIChildren were asked by Sisom if they felt different than other children . They alSecond, they reflected that their differences led others to stare at them, “the gaze of others” , which they acutely sensed, and caused their worries about feeling different to amplify. One child described how people gawked at her when she went out to the restaurant: “It’s that I often get stared at, at the restaurant, and I find that unpleasant” . Other children described strangers directly asking them questions about their bodies and having to explain their condition to others. For some, this was frustrating. In contrast, 1 participant did not let these types of questions hold her back from sharing knowledge with others about her condition:I just tell them to “Be careful! Because I could get hurt more easily than you.” I remember that there was someone that told me at Burger King: “Why are you more fragile than others?” I just explained to him that “Well, I have an illness, so my bones are more fragile and that if I fall it could break me...” and he was like “Ah...” Because [...] he kind of bumped into me.P11, 11 years old, type IV OIThird, they reflected that their differences led others to treat them differently. One child described how others were afraid to break her bones and that she was ostracized on a daily basis:I feel very lonely. No one wants to play with me because of my illness.P8, 7 years old, type I OIOther children expressed that people’s perceptions of the hardships of living with OI were overexaggerated. One child recounted the story of a stranger who wanted to give her a hug because she felt pity for her . Another child reflected on how he felt when his mother was overprotective of him:That’s annoying! I hate that. Be careful! You might get hurt.P7, 9 years old, type III OIHowever, 2 children viewed being different as positive, stating:Everybody’s differentP4, 8 years old, type IV OIBeing different from other kids is a good thing. Like, for example, I think that because I’m in a wheelchair, I can do things that other kids can’t do, and that, that part’s a good thing.P5, 10 years old, type IV OISisom OI paper prototype; however, OI was sometimes left out of the conversation altogether by the participants. For instance, when 1 child was asked what makes them feel different from other children, they commented on their age. When asked if there was anything else, they stated, “That’s it” . Every interview included children laughing, playing, and sharing, just as any other child would.All children demonstrated that they were more similar to others than they were different. The children shared their desires, wishes, and preferences just as any other child would. The goal was to engage children in the co-design of the They shared things about themselves that they found special, such as their likes: “We all love unicorns!” ; their dreams: “I want to be a vet.” ; and their hobbies:I am a HUGE Harry Potter fan! I am at the 5th book.P7, 9 years old, type III OIOI kid:One child, by having people get to know her, showed others that she was more than just an They just don’t know me yet. So like, [...] if a friend was there, then they wouldn’t look at me like that, cause they’d know that it’s my, I have a condition...P5, 10 years old, type IV OIAbout Me in which children could share what was unique about them. This child also emphasized that the avatar they create of themselves within Sisom OI be as realistic as possible. This view was shared by all participants: “You would like [...] that it looks the most like you...”  so that “You could see yourself...Through a computer technological program” . Many of the children had fun creating their avatars and customizing them:This child suggested the creation of a Sisom island called Ya, I like the color on that one!P9, 6 years old, type III OII’d like to put some shoes I like to wear. I got light up shoes but I’m not wearing them now...P10, 9 years old, type VI OIMany of the children reflected how they were the same as everyone else by normalizing their symptoms, stating:Everyone’s gonna feel like that, right?P7, 9 years old, type III OIIt’s pretty much [like that for] everyone.P3, 11 years old, type IV OIThey often described how they felt the same way others felt and shared many of the same experiences. Similarly, when 1 child was asked about her nightmares, she answered:I have more nightmares about like clowns and animals and stuff...That’s what scares me. Not really surgeries.P11, 11 years old, type IV OIThe same participant explained how she adapts her situation to be able to participate in events just like any other child. For instance, she takes her wheelchair out to go “trick-or-treating” to make the most of it:For example, Halloween, I would never do that with my walker! I would never be able! [...] By the time I get there wouldn’t be any candy left!P11, 11 years old, type IV OIRelating to Their Condition, children described their positive and negative interactions with their own condition and the health care system , discomfort , and surgical scars . One child got up on a chair to show from what height she might need to fall to break a bone . Another child, when approached about how he felt about his appearance, stated:The problem with OI is not how you look, it’s like, how you feel...is there any pain? Stuff like that! Not how you look! This is actually...That’s what makes sense to me.P4, 8 years old, type IV OIChildren with OI reported spending significant amounts of time in the hospital. As put positively by 1 child, “Sometimes I say the hospital and I are friends cause OI kids, we go to hospital a lot, for check-ups and stuff” . Children described many long and boring days in the hospital. One child expressed:...Some patients with surgeries, they like...I don’t know they like, get bored, in the, sitting in the room in a bed all day long.P4, 8 years old, type IV OIAnother child described the dread of staying overnight:Mostly I am scared of having pain when I turn,...I am scared of spending a bad night after my surgery [...] It’s cause you never know [...] if you’ll sleep, if you won’t sleep...P11, 11 years old, type IV OIChildren also missed their home, family, and friends. One child expressed not liking her treatments at the hospital because of “The fact that I’m far away from my sisters” . Another child described missing home during a long stay after her spinal surgery:We stayed there for a like a long time. Like one week, and I got sooo homesick. I missed like the city, the hustle and bustle, I missed my friends.P5, 10 years old, type IV OIIt was also common for children to travel from great distances to receive treatment, as it was for one child, whose mother had to stay home, in another province:Whenever I call mom I start to cry [...] She can’t come here cause she has to work.P6, 6 years old, type I OIThe hospital became somewhat of a home for many of these children who had formed a special relationship with the space and staff. For example, 1 child described his experience in the playroom:Back when we had surgery, here, we always loved to go to the playroom [...] The volunteers, I actually like the volunteers, like I made a friend [and...] we made a made-up movie together.P4, 8 years old, type IV OIThis special relationship also extended to the physicians, in whom the children placed a lot of trust to help them get better. One child described her fear of dying during surgery and that she placed trust in her physicians to help her through:I trust doctors...cause they want to help me feel better. [...] Surgeons, yeah.P5, 10 years old, type IV OIChildren described having to undergo countless unpleasant and painful procedures. When asked about medications, almost all the children expressed that they tasted horrible:Blerrrk! ...sometimes when I eat medicine, my taste buds are screaming at me like “WHY ARE YOU EATING THIS?”P5, 10 years old, type IV OIAnother common and dreadful experience was having to undergo surgery. One child enumerated 3 different reasons for requiring surgery because of OI, including coxa vara repair, scoliosis repair, and rerodding. She described her experience with surgeries:I have a lot of surgeries, when you have surgeries and you fall asleep for the first time, it’s like very difficult, cause I see a lot of nightmares.P5, 10 years old, type IV OIIt was something that she had a lot of experience with and to which she was now getting accustomed. This was similar to another child who showed off the many scars from a number of different surgeries . Another child emphasized how often he had surgeries:Sometimes like, if I get hurt and I hear my leg crack [...]. They go in, and then, if I didn’t have a rod in, they put a rod in, and that’s how they do it...I did this MANY times.P10, 9 years old, type VI OIChildren not only expressed that they felt discomfort during hospital procedures but also shared their pride in having gotten used to certain painful procedures. One child described being “Brave for everything” and doing a “Good job” by not crying during painful procedures, which she described as “another unhappy task” . Another child justified his painful experiences with their purpose:IVsintravenous accesses] are, they’re good. But like, so like you could have medicine...But, then again IVs do hurt a bit. But, they’re good so... because everybody excludes me. [...] I like playing outside even though I have this condition, because I have many friends at school.P7, 9 years old, type III OIAll children expressed a desire to do something they were physically incapable of because of a fear of getting hurt. For some children, this activity was eating. Some described not being able to eat tasty foods that were “Like, let’s say, sticky things...and things that are too hard”  and “like [...] bars, for example, I can no longer have them...”  because of an orthodontic mouthpiece they were required to wear for their OI. One child explained that OI prevented her from playing with her friends:Like for example...there, like, in my school yard, there’s like a big slide [...] where you climb up high, it’s like twisty. [...] so whenever I see them, my friends, they’re going down the slide, they’re having so much fun, it’s like, I can’t do it.P5, 10 years old, type IV OIAnother explained that his OI led to fractures that required him to wear a cast for healing. During this period, he was not able to play sports with his friends . This sentiment was echoed by another child who drew a picture to show how it felt to be excluded because of an injury:Like, if he’s looking at his cast, and his friends are outside playing street hockey...He’s in his room [...] It affects you to watch your friends play and you have to stay inside doing nothing.P11, 11 years old, type IV OIChildren also expressed how their perceived limitations may affect their future endeavors. One child expressed her desire to be a good dancer but that this was difficult because of the way her OI affected her bones. She reflected:Well, cause, I...I just wanna be a good dancer, and like, I wanna have strong bones...Sisom OI. She explained how a person with OI may want to become a police officer but would have to settle for working in the office answering phones instead of being out in the field.Another child stated that it would be important to include the question “Are you afraid that your handicap will prevent you from doing what you really want in life?”  in Some children also reflected on what their lives might have been like without OI. One recounted her daydreams and how she would “Go to any place [...] hang out with [her] friends alone, [...] help [her] mom a lot, [...and] go around [...] to places with [her] dad” . She reflected on needing help for some activities for which she was dependent on others. She also asserted her independence for other tasks. Most of the other children reported a similar balance.Ideas of feeling left out were expressed by all children. When prompted by Sisom “Do you ever feel left out?” children answered:A lot, because, because no one, almost no one, wants to be with me because of my disease.P8, 7 years old, type I OISometimes, [...] cause sometimes kids, they don’t wanna play with you, or, because of your condition they don’t wanna talk to you...P5, 10 years old, type IV OIThey overcame these feelings by finding independent activities and excelling in other areas, escaping through imagination, having good friends, and thinking positively.First, the children asserted their independence in several areas such as reading and journaling and taking time for themselves to be alone: “I want to write something on here!” . One child described how she turned to nature when her sister did not want to play with her: “So I just go outside and sit behind one of my trees” . Another child described how while she was dependent on others in some areas, she was determined to find ways to maintain her independence:When I’m at school, I have an aid, but she doesn’t go in the bathroom with me, she just holds the door in case I fall [...] I do my things, and I leave. She doesn’t come in with me, I do it all by myself.P11, 11 years old, type IV OISecond, building and maintaining strong friendships helped children overcome the feeling of being left out. One child referred to her pets when she reflected that “at least I have friends” . Another explained that good friends made feelings of exclusion tolerable:I do not like playing outside [alone] because everybody excludes me. [...] I like playing outside even though I have this condition, because I have many friends at school.P7, 9 years old, type III OIOne child reflected how she did not feel bad when her friends played without her at recess but always appreciated the time that they spent with her:They climb the spider webs, and all those things, and me, I couldn’t do them, so I stayed sitting at the table with my friends and we talked...Sometimes they left and they came back...To have fun a bit [...] I wasn’t going to prevent them from doing everything and say: “No you stay with me because I can’t do it” [Laughs].P11, 11 years old, type IV OIThird, they used their imagination to escape to different worlds by making up “a game like BOOM” , having an “imaginary friend” , imagining a “candy world, [...] a land full of candy and unicorns” , and “daydream[ing] about [the] future [...] working with animals” . Positive thinking was implicit in the attitudes of all children. One child embraced this philosophy when she explicitly stated:As a person, you always have to think positive. Cause if you think about the negative, then you’ll see life in a bad way. But life is not as bad as you think.P5, 10 years old, type IV OIAll the children experienced feelings of otherness, exclusion, and physical limitations, but they also celebrated their strengths and asserted their independence in various ways. Children were excited about their mobility improvements:I am quickly learning how to walk.P8, 7 years old, type I OI[running], that’s the next step.P7, 9 years old, type III OISome expressed confidence and pride in their current mobility status:I’m an expert driver with my wheelchair!P4, 8 years old, type IV OIYou know, I go really fast in my wheelchair.P3, 11 years old, type IV OIThis confidence allowed them to attend special events and show off their skills. One child participated in special Paralympic tournaments: “I won [...] I got three gold medals” . She also played soccer at her specialized school, where she felt comfortable being herself.Another child also played soccer and hockey with his friends . These adapted environments were important contributors in reinforcing feelings of inclusion and value.The children also celebrated their academic accomplishments. They highlighted how well they do in school: “I’m one of the best readers in my class!” . The children described their accomplishments with pride and confidence. One child explained how she was able to excel even in an accelerated program:I am in the intensive stream [...] So I do my sixth grade in six months...[Actually] five months! [...] So I have to go quickly! It’s like I’ve become a model!P11, 11 years old, type IV OIFinally, children with OI seemed to truly look out for one another. Their involvement in this study reflected kinship. Many participants understood the research implications for other children with OI. They highlighted the importance of including “everybody’s ideas, everybody’s advice”  and hoped:that kids will love it! Cause, we need to express it in a way that the public will love it [...] So we can make money and we can help this disease!P4, 8 years old, type IV OIThis kinship was further exemplified by one child who was very implicated in fundraising for OI. She made it a point to encourage other children with OI to keep their heads high:From my point of view, OI kids, they don’t think that they’re [...] awesome. [...] But you are awesome. I sometimes tell OI kids that, cause like, most of the ones that I know, they’re like young, like five or six, [...] So I tell them that: “You are awesome, cause you went through so much, and you’re so little!”P5, 10 years old, type IV OINot only did she celebrate her own strengths, but she also encouraged others to find their strengths and celebrate them.authentically listen and bring to light what children with OI shared when approached as experts in their condition was made possible by conducting a secondary analysis of qualitative data sources collected for the co-design of the Sisom OI paper prototype [Relating to Others, described the balance between feeling different versus feeling similar to other children. The subthemes were Common OI Experience, Feeling Different, and Feeling Just Like Others. The second, Relating to Their Condition, described children’s positive and negative interactions with their own condition and the health care system. The subthemes were Understanding Their Condition, Special Relationship with the Hospital, and Difficult Treatments and Procedures. The third, Reflecting on Capabilities, described children’s recognition of their strengths and limitations. The subthemes were Perceiving Limitations, Overcoming Isolation, and Celebrating Strengths.Efforts to rototype . This strototype ,27. ThroRelating to Others, children described a balance between feeling different and feeling similar to other children. They also expressed a concern about the perception of others. This has previously been described in other studies of children with OI [Children with OI had a unique way of maintaining balance in their lives. This was demonstrated through all three of the themes. First, in  with OI ,38. An i with OI . Another with OI ,40.Relating to Their Condition, children described a balance between the positive and negative aspects of living with OI. Children’s depth of understanding and moral awareness can range from rich sophistication to simplistic matter-of-factness [getting used to painful procedures was something that children with OI have expressed in other studies [getting used to pain was expressed by the children as a proud adaptation to a difficult aspect of living with OI. Another way that children overcame the negative aspects of being hospitalized was by reflecting on the positive relationships they had developed with clinicians and volunteers, which other children have reported [Second, in factness . Childrefactness . Indeed,factness ,38. Tolereported ,41. It hReflecting on Capabilities, children described a balance between perceiving their limitations and celebrating their strengths. Feeling left out because of the fear of fractures or physical limitations was a major element of this theme and has been explored in other studies [taking life in stride and using their positive outlook to overcome feeling different and feeling left out and making the best of every day [Finally, in  studies ,38,42. D studies ,42. Our  studies . Childreplace into a child’s space [Sisom OI is yet to be developed, tested, or integrated into practice. Therefore, these study findings offer only preliminary insight into the types of discussions that may unfold from the future use of Sisom OI in practice. As OI remains a rare disease with few clinicians encountering a child with OI over the course of their career, there may be some reluctance to use Sisom. Offering training and delineating potential responses to children’s expressed concerns may help integrate this novel, interactive, computerized tool into practice and contribute to the transformation of children’s rightful space in their health care systems [Sisom may contribute to transforming a child’s ’s space  by invit’s space  and show’s space . Sisom a systems ,35.child’s perspective, placing the child in the center of their experience. These children had many things to share about their experience, as noted by other chronically ill children [In this study, the partnership created between the interviewer and the child successfully elicited and highlighted the children . Althougchildren ,16. SisoSisom OI. Therefore, they were not directly prompted to share their OI experiences, unless prompted by the interviewer. The questions posed in Sisom were not tailored to specifically capture the experiences of children with OI. This may have led to significant data gaps. Future studies should be conducted to specifically aim to understand children’s perspective on their OI.The children in this study were prompted to give their opinion on Sisom to co-design Furthermore, the involvement of parents and legal guardians in the interviews had, in some cases, a muting effect on the child. Instead of giving space for their child to answer the questions independently, some took it upon themselves to answer for their child. In some cases, this prompted the child to express their feelings and share their experiences, whereas in other cases, this caused the child’s voice to be lost. Further studies should consider how to highlight the child’s voice by emphasizing on the child’s answers and constantly reemphasizing the purpose of the study to the parents involved.Sisom OI and our overall approaches to offer care that responds directly to their needs and empower them to be active partners in their care.This study highlights the richness of the experiences shared by children who are approached as experts in their own condition. These children had valuable information and insights to share regarding their day-to-day lives and the factors in their lives that both hinder their development and support their endeavors. The study findings offered a glimpse of what it means to grow up living with OI but also showcased a novel approach to gain their perspective. The children’s inputs will be further used to advance the development of Sisom OI to ensure that meaningful aspects of life with OI are included in the app and attended to in practice. At present, the Sisom OI paper prototype has been developed [Sisom OI paper prototype, 57 new symptoms were generated. The relevant symptoms addressed children’s thoughts and feelings about hospitalization and their wishes for participation in their own care. The new symptoms addressed fractures, body image, and social isolation related to difficulties with accessibility and intimidation. Therefore, these findings, in addition to the themes identified in this study, will be used to inform the next phase of Sisom OI development with end user partnerships, stakeholder buy-in, and the necessary funding. We expect to build the prototype; test for usability; pilot for feasibility; and evaluate the integration of Sisom OI into the hospital, home, and school settings.The study findings will be also used to inform the development, verification, validation, and evaluation of eveloped . AlthougThis co-design process provided children with OI the space to not only contribute to the development of the end product but also to eloquently describe their experiences. These findings, based on the description given by the children themselves, offer us a unique understanding of what it means to grow up with OI.


Psilocybin is a naturally occurring psychedelic substance present in a variety of Psilocybe mushroom species . It has Social phobia is marked by a persistent fear of embarrassment or humiliation in social situations. Anticipatory anxiety and avoidance occur when an individual is under scrutiny during public speaking or other public activities. This highly prevalent and chronic disorder significantly impairs psychosocial functioning, with pharmacological and psychosocial treatments showing limited results ,18. HoweThis article reports on a 16-year-old male patient treated in a psychiatric clinic with the symptoms of social distancing, increased intensity of anxiety, and poor school performance. He experienced learning disabilities, lack of motivation for schoolwork with poor academic results, and isolation from his peers and teachers. The transfer to a new school failed to bring about any improvement. The adolescent started attending a psychotherapeutic group but found it difficult to communicate with other members and express his feelings, so he often avoided sessions due to anxiety. He occasionally consumed marijuana, which failed to reduce anxiety and improve his functioning. After being offered psilocybin by a friend, he consumed two grams of Psilocybe mushrooms, corresponding 20 to 30 mg of the substance, on three separate occasions over an 18-month period. The patient described the effect as a feeling of sublimity and enlightenment. After this experience, he more frequently participated in group activities, communicated better with other group members, expressed emotions without inhibition, and felt less anxious. Such rapid and evident improvement of group psychotherapy results has not yet been reported. In fact, it has not been shown that psychotherapy alone could lead to such sudden and long-term changes in patients’ mental status.The patient's feelings of “connection with people around him” and “sublimity” can be explained by the activation of certain neural systems of the brain, particularly the so-called seeking systems, which play a role in fighting depression and anhedonia. In other words, people are motivated to accept pleasure and avoid discomfort. These neuroanatomical changes form the basis for opioid addiction. Once this system is activated, the experience of “solving the problem of anhedonia” remains in the memory engrams and is quickly and easily accessible. Psilocybin increases the concentration of extracellular serotonin and dopamine in the nucleus accumbens and the median prefrontal cortex. This system, particularly nucleus accumbens, is an important part of the “seeking system.” In addition, the medial bundle of the forebrain, which is connected to the nucleus accumbens and is located in the immediate vicinity of the median prefrontal cortex, could be simultaneously activated. Accordingly, even if these neural areas are stimulated only once or twice, in the patient’s memory an impression is created that “everything will be fine.” The guilt that the patient experiences helps him to refrain from taking this substance again. However, he is aware that by consuming psilocybin his problem was “magically solved.” The feeling that “everything can be fine” continues to exist only at the level of an idea due to the stimulation of the mentioned neural circuits and nucleus. The same system is also stimulated by frequent psychotherapeutic treatment. During psychotherapeutic treatment, a sense of satisfaction arises from repeated conflict resolution or pleasure due to identifying with the psychotherapist. In addition, separation and reuniting subconsciously suggest that although the patient is alone, he or she will be reconnected with his favorite object. In this way, a so-called safe attachment is established, which creates new collaterals and dendritic shoots in the mentioned neural pathways. Ideally, completed psychotherapy enhances “collateral and dendritic” neural pathways that increase patient’s confidence in other people, enabling him or her to function in everyday life ,7,22-27.Conventional therapy often shows limited effectiveness in resolving the symptoms of anxiety and depression ,9,16,18.Although psilocybin use entails some level of risk and abuse potential, there is no strong evidence of physical or psychological dependence, and it can be considered safe under medical supervision ,2,6,22.


Mentalizing is the ability to represent mental states to navigate the social world. A reduced mentalizing ability is a risk factor for a variety of psychological issues. Several studies indicated deficits in social cognition in bullies and victims, specifically in mentalizing anger. However, only a few studies investigated mentalizing abilities related to both anger and happiness in pre-adolescence. Our study investigated possible differences in the ability to mentalize anger and happiness in preadolescent bullies and victims, compared to a control group. We interviewed 104 preadolescents  and administered the Olweus Questionnaire to identify bullies and victims. We applied a narrative approach to investigate the mental state language referred to anger and happiness. The results indicated a reduced ability to mentalize anger in bullies and victims compared to controls. Both bullies and victims tended to consider anger and happiness predominantly as behavioral conditions rather than a state of mind. These results highlight the need to promote effective intervention programs to prevent bullying by enhancing appropriate mentalization of emotions in pre-adolescents. Mentalizing is the ability to think about one’s own and others’ mental states . It is aThe ability to mentalize emotions is a component of a broader emotional competence. It allows obtaining access to emotions as affective mental states. It promotes an understanding of interpersonal behavior and self-regulation .According to Saarni , emotionSome studies investigated the ability to mentalize emotions at the beginning of adolescence.These studies confirm the framework of the hierarchical model of Pons, Harris e de Rosnay , which hOther studies considered the role of education and individual differences in the development of emotional competence from a developmental perspective ,11 and aLimits in parental mentalization might be a risk factor to develop a variety of psychological disorders, such as antisocial , borderlBullying is a phenomenon characterized by negative actions toward a peer, with the intention to hurt . BullyinRecent studies highlight the main cognitive and emotional mechanisms that characterize bullies. The model of the “Social skills deficit”  indicateVictims also show an atypical social information processing. Both bullies and victims describe “bullying” as some scenes that controls define simply as a playful fight. According to Crick e Dodge , it mighAccording to Lemerise and Arsenio , bulliesBullies appear to not feel guilty for their actions possibly due to the mechanism of social disengagement . The lacSutton, Smith and Swettenham  indicateSeveral studies indicated significant differences in the ability to mentalize emotions in bullies, victims, and controls. Aggressive children are less accurate in identifying emotions compared to prosocial and altruistic classmates . ParticuEven though it is still not clear why a low level of mentalization is associated with a conduct disorder in children, it might be that an emotional dysregulation, particularly a predisposition to feel anger is associated with low levels of mentalization. Anger is associated with low self-awareness.Studies of bully families indicate that domestic violence and family conflict, characterized by high emotional manipulation, coercion, and unpredictability, put children at risk of developing emotional dysregulation and impulsivity ,47,48. DIndeed, victims’ families are characterized by high levels of cohesion and overprotection ,48, highSince mentalization is a key ability in successful social interactions, bullies and victims might lack the ability to mentalize emotions like anger and happiness, maybe due to a difficult familiar culture, which tends to emphasize the expression of certain emotions and discourage the expression of others, with a detrimental effect on the awareness, the definition, and the narration of the emotions. Despite the relevance of the ability to mentalize anger and happiness for successful social relationships, no study so far, to the best of our knowledge, investigated this ability in bullies and victims.Our study aims to fill this gap in the literature, by investigating possible differences between bullies, victims, and controls (students not involved in bullying in any role) in the ability to attribute mental states referred to the emotion of anger and happiness. Our hypothesis is that as compared to controls, bullies and victims will be less able to mentalize these emotionsn = 46) and 55.8% females (n = 58), age ranged between 13 years  and 14 years . Data collection took place in a suburban area of Cagliari , where the risks of school drop-out, psychological, and social malaise, drug abuse, and unemployment were high [This study involved 104 pre-adolescents in middle school, 44.2% males . Differences between categories were analyzed by a χ2 test with a level of significance of 0.05.The Olweus Bully/Victim Questionnaire (OBVQ)  is an anSeveral studies showed evidence of the validity of the OBVQ using different methodological approaches . The resThe questionnaire starts with two global questions where students could identify themselves as victims or bullies: “How often have you been bullied at school in the past couple of months?” (victims), and “How often have you bullied at school in the past couple of months?” (perpetrators). The answers can be coded on a five-point scale from 0 to 4  .Children who had been bullied “2 to 3 times a month or more” were classed as victims. Those who had bullied others “2 to 3 times a month or more” were classed as bullies. Then, children who had both bullied others, and been bullied, at least “2 to 3 times a month or more” as “bully-victim”. Whereas those who had responded that they “have not” been bullied/not bullied other students or have been bullied/have bullied other students “only once or twice’’ are considered “non-victims or non-bullies” . Those lThe narrative tool of Grazzani, Antoniotti, and Ornaghi  includesDescribe an episode of your life in which you have been angry.Describe what is anger for you.Describe an episode of your life in which you have been happy.Describe what is happiness for you.This approach includes four open-ended questions, as follows:We coded the participants’ answers according to the method used by Montirosso, Pupino, and Borgatti , which a(n = 26), victims were 15.4% (n = 16), bullies-victims 3.8% (n = 4) and students “non-victims or non-bullies” (controls) were 55.8% (n = 58). In our analysis, we did not compute the answers of the bullies–victims, which were very rare (n = 4), and which have been considered in previous studies as a source of high variability [2 = 0.288; α > 0.05; ns). Victims were 43.75% males and 56.25% females  and controls were 48.3% males and 51.7 females . Age was not considered as a significant variable because all students who were interviewed were in third year of secondary school and were between 13 and 14 years old. Among the invalid questionnaires (poorly completed or incomplete), those of four students over the age of 14 were eliminated and were not considered part of the overall sample.The results indicated that bullies were 25% iability . AnalyseHere, we indicated the results of the first item, which asked the participants to describe an episode related to anger, in the three groups of bullies, victims, and controls .2 = 3.04, α > 0.05, ns). As compared to the control group far more bullies reported problems with classmates . On the contrary, as compared to controls, fewer victims reported having problems with their classmates . It seems that, within the context of the social relationships with classmates, bullies experience more anger compared with victims and controls. Victims tend to feel less angry compared with bullies and with peers not involved in bullying (controls). It might be of interest to explore in detail how the three groups mentalize anger.The category indicated by bullies as most associated with anger was “problems with classmates” (37.1%). The category indicated by victims and controls as most associated with anger was instead “problems with friends” . As compared to controls, fewer bullies attributed anger to mental states  and as “thing or moment” , compared to controls. Bullies tended to define anger mainly in terms of behavior or physical state ;“When someone makes me angry, I want to hit him” (anger as behavior state);“When I’m angry I feel like bursting” ;“Anger is an emotion that occurs when I believe others want to boss me around” .Below are some examples of the definition of anger in bullies: “Anger is an emotion that makes me believe I am right when I believe I am experiencing injustice”.Below is an example of the definition of anger in a student not involved in bullying (controls): As you can see, there are many references to mental states. These results as a whole indicate a bullies’ difficulty in considering anger as a mental state.Here, we indicated the definitions of anger in the victims and in the control group, in the second item that investigated the ability to mentalize anger .2 = 30.72, α ≤ 0.05). Victims considered anger more in terms of behavior or physical state  or as “thing or moment” , compared to controls. Below are some examples of the definition of anger in victims:“Anger is an ugly thing” (anger as a thing or moment);“Anger leads me to distance myself from certain companions” (anger as behavior state);“I think it’s not right to feel angry” .As compared to controls, fewer victims considered anger in terms of mental state . Controls used mainly a moderate number of terms related to mental states (44%), in the range (15–25). The victims did not differ compared with controls in the number of terms used to refer to anger , since they used the 50% of terms in the intermediate category (15–25 words) compared with controls (44%).Bullies used a significantly lower number of terms referred to as anger (50%) in the category (4–14) compared to controls  compared with controls. They also claimed to be “rarely happy”  in their interactions with parents and friends  compared with controls.Bullies associated less happiness with “presents, parties and travels”  compared to controls.Victims, like bullies, tended to associate less happiness to “presents, parties and travels” . Bullies tended to refer more to happiness as a “behavior or physical state”  and as a “thing or moment”  compared to controls. As compared to controls, fewer bullies attributed happiness to mental states .“When I’m happy I feel like screaming” (happiness as behavior state).“I think I’m happy when others respect me” .Below are some examples of the definition of happiness in bullies:These results indicate bullies’ difficulty in considering happiness as a mental state.Here, we indicated the definitions of happiness in the victims and in the control group, in the fourth item, which investigated the ability to mentalize happiness .2 = 15.42, α ≤ 0.05). Victims considered happiness more in terms of behavior or physical state , compared to controls.As compared to controls, fewer victims considered happiness in terms of mental state ;“When I’m happy I want to tell everyone” (happiness as behavior state);When I’m happy I feel light” ;“When I’m happy, I think everything will be fine” .Below are some examples of the definition of happiness in victims:Here, we indicated the number of terms that bullies, controls, and victims use to refer to happiness, expressed in terms of percentage , in resp2 = 19.62, α ≤ 0.05). Most of the of the controls (40%) used an intermediate number of terms (13–23), while most victims (40%) used a significantly higher number of terms  to refer to happiness, compared to controls (30%). Most bullies used very few terms to refer to happiness (2–12) compared to controls (41% vs. 20%; χBoth bullies and victims show difficulties in defining happiness in terms of mental states, focusing mainly on behavior and physical states compared to controls. However, victims tend to use a higher number of terms to define happiness, which might indicate that they are more able to talk about emotions. Bullies use a very low number of terms to define happiness. It is possible that, even though bullies and victims share some level of difficulties in referring to mental states, bullies might be more resistant to talking about emotions.This study investigated how pre-adolescents mentalize the emotions of anger and happiness. The results indicated atypical social cognition both in bullies and victims but not in controls. Specifically, bullies associate anger mainly with socio-relational problems with their classmates. On the contrary, victims rarely associated anger with these problems, with a lower frequency compared with controls. It seems that bullies get angry too much in the interactions with their classmates, while victims get angry very rarely. These results are in line with previous studies, indicating an atypical perception of anger both in bullies and victims ,30.Morosan, Fonseca-Pedrero, Debbane  interprePrevious studies indicated that the phenomenon of hypo-mentalization might arise from an inability of the parents to be emotionally attuned to their children, maybe due to higher levels of stress and/or familial conflict ,42. PrevOur results shows that victims have the same difficulty in metalizing anger. They tend to refer to this emotion in terms of a “thing” or a “moment”. It is possible that victims learned to avoid anger with the classmates, probably because it is perceived as dangerous outside of their family. Previous studies on the familiar background of the victims ,48,51 shFrom this point of view, our study has some limitations. First, it is necessary to obtain additional data about the socioeconomic and family background of bullies and victims to better understand some of the findings. It would also be interesting in future research to use other quantitative tools to explore the role of other important emotions such as fear and shame in victims and guilt in bullies. In summary, the results of our study integrate the data already present in the literature, which highlights difficulties in mentalizing anger in bullies and victims ,24,25,28This contribution has practical implications for prevention of distress in preadolescents and promotion of well-being at school. It is necessary, therefore, to apply practical guidelines in terms of addressing the bullies’ and victims’ limitations of mentalizing emotions, trough the socio-affective education at school . For vicFor bullies, some preventive measures may be created to promote awareness of anger and teach them how to handle aggressive behavior and empathize with their peers.The results of our study indicate the need to define effective intervention programs to prevent bullying by promoting adequate mentalizing emotions. The construct of the mentalization is essential to understand the development of the ability to regulate emotions in preadolescence, promoting the reflective function of the mind . Finally