To investigate the acceptability of the Cytosponge, a novel sampling device to detect Barrett's oesophagus (BE), a precursor to oesophageal adenocarcinoma (EAC), among people with risk factors for this condition.A qualitative study using semistructured interviews and focus group discussions. Data were explored by three researchers using thematic analysis.Community setting in London, UK.A recruitment company identified 33 adults  aged 50–69 years with gastro-oesophageal reflux disease (GERD), a risk factor for BE. The majority of participants were white British (73%). The focus groups were stratified by gender and education. 10 individuals were interviewed and 23 participated in four focus groups.3 key themes emerged from the data: the anticipated physical experience, preferences for the content of information materials and comparisons with the current gold-standard test. Overall acceptability was high, but there was initial concern about the physical experience of taking the test, including swallowing and extracting the Cytosponge. These worries were reduced after handling the device and a video demonstration of the procedure. Knowledge of the relationship between GERD, BE and EAC was poor, and some suggested they would prefer not to know about the link when being offered the Cytosponge. Participants perceived the Cytosponge to be more comfortable, practical and economical than endoscopy.These qualitative data suggest the Cytosponge was acceptable to the majority of participants with risk factors for BE, and could be used as a first-line test to investigate GERD symptoms. Concerns about the physical experience of the test were alleviated through multimedia resources. The development of patient information materials is an important next step to ensuring patients are adequately informed and reassured about the procedure. Patient stakeholders should be involved in this process to ensure their concerns and preferences are considered.ISRCTN68382401; pre-results. This is the first study to qualitatively explore the acceptability of the Cytosponge test among members of the public who may be at increased risk for Barrett's oesophagus.The sample was diverse in terms of gender and educational background.Participants were recruited using a market research company, so results may represent the views of particularly motivated individuals and should be carefully generalised to the wider patient population.Participants were not attending a medical appointment, so their attitudes towards the Cytosponge were hypothetical and may not reflect their opinions in a clinical setting.Quantitative data on the acceptability of the Cytosponge and its influence on test uptake were not assessed, but this has been previously examined in a clinical setting.In the UK, 8784 individuals were diagnosed with oesophageal cancer in 2013.4–6Risk factors for BE include male gender, Caucasian ethnicity, over 50 years of age, and having a family history of BE. Lifestyle factors include being overweight or obese, high abdominal fat, smoking and drinking alcohol.14Identifying patients with undiagnosed BE may reduce mortality; however, routinely investigating all patients with dyspepsia and GERD using endoscopy would be time and resource intensive, and not feasible in the National Health Service (NHS).The acceptability and accuracy of the Cytosponge-TFF3 test for screening for BE has been tested in several studies, including the Barrett's Oesophagus Trial 1 (BEST1), a cohort study in patients with previous prescriptions for acid suppressants in a UK primary care setting,To ensure information on the procedure will be presented to BEST3 participants in the most accessible manner, and to encourage rapid implementation in clinical practice at a later stage, public perceptions of the procedure need to be explored in greater depth. The aim of this study was to obtain a detailed understanding of the acceptability of the Cytosponge-TFF3 test in a sample of individuals with GERD. This population was chosen because they reflect the population to which the test will be offered as part of the BEST3 trial and if it is implemented in routine primary care.The study was advertised to adults aged 50–69 years by a recruitment company email, and respondents were screened on the telephone for eligibility. This age group was selected as this population will be eligible for the Cytosponge test within the BEST3 trial. GERD severity was assessed using the GERD impact scale.The first 10 eligible respondents were invited to participate in a one-to-one interview with a researcher (MF). The interviews were used to inform the focus group presentation. After 10 interviews were completed four focus groups were arranged. The focus groups were stratified by gender  and education (high vs basic). Participants were recruited until data saturation was reached and no new themes emerged from the focus groups or interviews.19Semi-structured interviews are an effective method for obtaining detailed opinions of an isolated individual, whereas focus groups generate discussion from multiple perspectives. A combination of both face-to-face interviews and focus group discussions were used for this study to explore how individuals perceived the Cytosponge test when they were alone and in a group setting. Interviews and focus group discussions took place in meeting rooms at the Wolfson Institute for Preventive Medicine, Queen Mary, University of London. Written consent was obtained at the beginning of the interview or focus group by a female research assistant trained in qualitative research . The interviewer had not met any participant prior to the study, and participants were given little information beyond her research interests. MF had no personal interest in oesophageal cancer research that would influence her behaviour towards the participants. No other person was present within the interview or focus group. A demographic and lifestyle questionnaire was completed prior to starting. This assessed GERD severity and management with the GERD impact scale,20The interview schedule was designed by the research team and tested with three adults aged over 50 years to ensure participants could follow all questions in the different sections. In response to these test interviews background sections were expanded or simplified where necessary and a small number of questions about the Cytosponge were added. These interviews, however, were not recorded or included in the analysis.The interview schedule had six sections, also see online 10.1136/bmjopen-2016-013901.supp1supplementary documentA presentation was created by the research team. This followed a similar structure to the interview schedule, although questions relating to the topic of ‘Cancer Prevention’ were removed, as participants had difficulty answering these in the interviews. The presentation contained more visual cues than the interview and participants could read the text, which was in bullet-point format, and projected onto a screen  within qualitative data was used for the analysis.Thirty-three individuals participated in the study, 16 women and 17 men . Ages raParticipants expressed enthusiasm about the Cytosponge, with most indicating they would take the test if invited. The three major themes identified were the anticipated physical experience, information preferences and comparisons with endoscopy. Subthemes are presented below, along with representative quotes.Individuals discussed their anticipated physical experience of the Cytosponge test. This included swallowing the Cytosponge and extracting it. The anticipated physical experience appeared to be shaped by both handling examples of the capsule and sponge, and watching the video of the test being carried out.It's smaller than I imagined … The capsule is just like a normal vitamin capsule, so that's perfectly fine Based on initial images and verbal descriptions most individuals imagined the capsule to be bigger than its actual size. People expressed surprise and felt reassured after handling a Cytosponge. It was generally felt that the act of swallowing the Cytosponge capsule would not be problematic, because it was of a similar size and shape to other tablets they take regularly.It's just the string following it down I think I might have a problem with. I’ve never actually swallowed a ball of string A few people were concerned about swallowing the string attached to the capsule.You’re going to feel it, it's going to be as if somebody's got their fingers and scratching the inside of your windpipe After feeling an expanded Cytosponge in the demonstration, participants said it was rougher than they expected, with many comparing it to a ‘Brillo pad’. As a result, there was concern that an expanded Cytosponge would damage their oesophagus when it was extracted.I’d be frightened that I’d throw up. I’ll be honest Some people were worried they would gag or even vomit when the Cytosponge was withdrawn from the stomach.What if it got stuck? Because you know sometimes when a sweet goes down the wrong way…and it gets stuck? That is scary A consistent concern was the possibility of the string breaking and the Cytosponge getting stuck in the oesophagus or stomach.In my mind I was thinking of you know [removing the sponge would be like] catching a fish After watching the video, individuals were more positive about the Cytosponge test compared with their initial reactions. The main reason for this attitude shift was because the extraction of the sponge was considerably quicker than expected.He didn’t show any gagging or anything. He was absolutely fine Additionally, the ease with which the patient swallowed the Cytosponge was commented on. The fact the patient did not gag during its extraction was considered comforting.He looked very relaxed, surprisingly… I think I'm sort of happier now, after watching the video Finally, people commented that seeing the patient in the video looking relaxed put them at ease.Individuals differed in their preferences for what information they would receive if they were asked to do the Cyosponge test. This included the amount of information they were given on the link between GERD, BE and EAC, on the Cytosponge test itself, whether they were shown an expanded Cytosponge before taking the test, and the optimal timing for informing patients about endoscopy referral. People also discussed their preferred format for communicating information.I’ve never taken it [GERD] to the next step in my mind Most participants had no or low awareness of the relationship between GERD, BE and EAC.If you’re reading something with ‘cancer’, you’re frightening them anyway… You say cancer, people won't take the pill Some people said they would want to be told GERD can lead to EAC before they took the Cytosponge test, while others said they would not want to know about the association. Some perceived that discussing a link with cancer may frighten patients and reduce uptake.I'd want to know everything you told us here . … What it does, how it does it, why you're doing it? Most participants felt the amount of information provided about the Cytosponge test during the interview or focus group was sufficient for them to decide whether they would have the Cytosponge test.If there was any side effect, whether it has to be done on an empty stomach, like, you know, should it be done in the morning? In addition, some people wanted to be informed about other details for example whether the test had to be performed on an empty stomach. There was also demand for information on side effects, even though they felt that those would probably be unlikely or mild.Yeah, so what happens? Once it goes to the lab, how long will it take before you find out whether you've got it? Other information people felt should be included regarded timings, specifically how long the test takes in total, how long the sponge stays in the stomach and the time it takes to receive results.I'd want to know how, like I say, I'd want to know how accurate it is as well. There's no point doing it if it's not accurate Furthermore, individuals felt that information on the accuracy of the test should be included.If they don’t tell you, you’re going to be in for a fright when you pull it out of your throat During the demonstration, some participants expressed surprise at the appearance of the Cytosponge after the capsule had dissolved and it had expanded. They felt that prospective patients would be unnerved by its change in appearance if they had not been shown how the Cytosponge looks after it has been extracted before the test.They wouldn’t do that with any other test, would they? They wouldn’t let you feel the needle before they took your blood One person conceded this may not be necessary, and that a similar approach would not be taken with other medical procedures.I think it would be nice to be offered the choice. Maybe be asked ‘would you like to see how it looks? Another approach would be to offer each patient a choice.I imagine it's just like NHS screening actually, when you have a mammogram you’re actually told what the programme is There was debate over whether or not one should be told before taking the Cytosponge test that a positive result will necessitate further investigation. Some people insisted they would expect to be fully informed about the whole process at the outset, and compared it with the existing NHS screening programmes.I think that just having one test is scary enough for someone, thinking they might have cancer. So just stick to that test, and when the results come back, then they can be told what the next step is Others felt they would prefer to be told this information in a step by step approach, only being informed about the need for endoscopy after they have received a positive result. This preference was perceived to prevent unnecessary anxiety.A link within the leaflet that you can actually go and see that video of the guy. I think that's really important Peoples' preferences for the modality in which information about the Cytosponge test was delivered varied. Suggestions included pictures, a leaflet, a website and a video. The preferred modality was an information leaflet with a website link to the video of the test being carried out.Sometimes if it's late at night and my brain has, sort of, had enough for the day, I’d much rather just watch a little clip, you know I can get to see, and I can listen, I don’t have to read… reading is something you really have to really concentrate. So, the clip is almost doing it all for you A video was perceived by some individuals as being easier to understand than written information.I would like to see him saying how he feels the next day… just another follow-up video…you know, ‘I’ve got a really bad sore throat, and, I feel a bit raw down there One participant mentioned that she would also like to see a follow-up video of the patient so that she would know what to expect after the test had been performed.While the Cytosponge test is not intended to replace endoscopy, it was felt that the new device was preferable physically, practically and economically.The last [endoscopy] the nurse had to practically sit on me to stop me moving, because it was so unpleasant. And I was just regurgitating all this sort of yellow stuff, it was like something from a horror film [The Cytosponge] is such an innocuous test. You swallow a pill, you pull it out, two weeks later, done. I can’t see anybody saying no to that Fifteen participants had previously undergone endoscopies for their heartburn, and almost all reported an unpleasant experience. By comparison, the Cytosponge test was perceived to be a more comfortable procedure.It's quicker, my doctor can do it and there's no messing around, no hospital appointments Individuals were enthusiastic that the Cytosponge test would be a quicker procedure than endoscopy, could be carried out by their general practitioner, and would not require an anaesthetic.You can walk out of the doctor's surgery… you can get on with your everyday life The fact that people would be able to resume their everyday activities immediately after the procedure was also seen as a benefit.That's going to be an awful lot cheaper to do than an endoscopy at an hour a go with a gastroenterologist A minority of people considered the superior cost-effectiveness of the Cytosponge test, and the benefits this would have for the healthcare system.In this sample of UK adults with GERD, the Cytosponge test was considered to be an acceptable and simple test to detect BE. Three key themes emerged from the data, including the anticipated physical experience of the test, preferences for the format and content of information, and comparisons with the current gold-standard test. These data can be used to inform the development of information materials and assist clinicians communicating with the public about the test.Initial reactions to the Cytosponge test focused on the anticipated physical experience. Common concerns included worries about swallowing the capsule and string, the texture of the sponge once the capsule had dissolved, and the potential for the device to break and become stuck. Despite these worries, nearly all participants were reassured by seeing examples of the device and a video of a previous patient undergoing the procedure. The observation that participants felt more inclined to take the Cytosponge test after watching the video demonstration reflects previous research into the use of multimedia to promote health behaviours,Participants' information preferences varied. Opinions differed on how much information should be presented on the link between GERD, BE and EAC, test outcomes, and whether an example of an expanded Cytosponge should be shown. The content of health information materials is generally driven by the ethical and legal responsibility to promote informed decision-making.26Overall, participants felt that the Cytosponge would be preferable for potential patients compared with the current gold-standard test, endoscopy. The device was considered superior in terms of the physical experience, the practical simplicity and the potential for economic savings to the healthcare service. Initial concerns about the device notwithstanding, public enthusiasm for the Cytosponge test is encouraging. On the basis of this initial acceptability study, recruitment of patients to the BEST3 trial and subsequently implementing the device within a primary care setting is unlikely to face insurmountable barriers from the public.Our study is the first to explore in-depth attitudes towards the Cytosponge test in a sample of adults with GERD. The use of interviews and focus groups provided a rich data set consisting of opinions expressed individually as well as in a group environment. The sample was diverse in terms of educational background and gender, allowing multiple perspectives to be considered. The study did have limitations. The sample was recruited using a market research company, and respondents may have been particularly motivated or interested in the topic. We did not collect quantitative data on acceptability or attitudes towards the test. Finally, the participants were not attending a medical appointment and therefore their attitudes towards the Cytosponge test were hypothetical, and may not reflect the opinions of patients in a clinical setting.This study has several implications for clinical practice. Both for BEST3 and if the Cytosponge test is implemented in routine care it will be important for information materials and health professionals to reassure patients about the procedure. In particular, concerns about the size of the device, the string breaking and the physical sensation on the throat when the device is withdrawn should be addressed. The speed with which the procedure can be completed should be emphasised to prevent exaggerated assumptions about a lengthy extraction. The study showed individuals hold strong preferences regarding the amount and format of information they are given. Consequently, health professionals should consider eliciting information preferences during the consultation. Finally, we demonstrated a need to raise awareness of the link between GERD, BE and EAC. Clinicians should not assume that patients are aware of the associations, and should carefully explain the context when discussing why recurrent GERD symptoms should be investigated.This qualitative study revealed adults with GERD considered the Cytosponge test to be acceptable physically, practically and economically, as well as being preferred to endoscopy. If the device is implemented in routine clinical practice, it will be necessary to reassure patients about the Cytosponge and provide materials that meet the information needs of the patient group.


With small effect sizes, the subclinical ADHD group showed reduced EE scores on the EQ and a more male social cognitive profile. This result was not influenced by sex or ADHD subtype. This study points to a relationship between traits of ADHD and the emotional aspect of empathy, whereas more complex aspects of empathy were unrelated. These findings should be corroborated in clinical patients with ADHD, employing neuropsychological tests rather than self-report questionnaires.Studies in children with ADHD suggest impairments in social cognitive functions, whereas studies in adults with ADHD are scarce and inconclusive. The aim of this study was to investigate the relationship between ADHD traits and self-reported social cognitive style in a sample of adults from the general population. For this purpose, a community sample of 685 adults filled out online self-report questionnaires about ADHD symptoms , social cognitive functioning and friendships. The Empathy Quotient (EQ) with the subscales Cognitive Empathy (CE), Emotional Empathy (EE) and Social Skills (SS), and the Systemizing Quotient (SQ) were included for measuring social cognitive style and the Friendship Questionnaire (FQ) for the quality of friendships. Participants who met the DSM-5 criteria on the ARS (‘subclinical ADHD’;  Attention deficit hyperactivity disorder (ADHD) is not only associated with symptoms of inattention, impulsivity, impaired inhibition and hyperactivity , measuring the social engagement and the enjoyment and importance of friendships  differed from matched controls in their reports of social cognitive style. It was hypothesized that people with subclinical ADHD would present with a more ‘autistic-like’ cognitive profile, with lower scores on EQ and FQ and higher scores on SQ and brain type . The subscale scores  were explored in order to get more refined insight into the different aspects of social cognitive style. In order to draw conclusions on the impact of the cognitive profile on the quality of friendships, it was furthermore explored how reports of social cognitive functioning (in interaction with ADHD symptoms) in a community sample relate to self-reports of the quality of friendships.A community sample of 685 adults  in the age of 16–84 years and a mean age of 33 years participated in the survey for this study. This sample was previously included in a psychometric analysis of the Dutch EQ and SQ-R that is described elsewhere  of the sample fulfilled the criteria of a subclinical DSM-5 diagnosis of ADHD based on both the current and retrospective ARS. This prevalence differed significantly between the sexes  = 8.0, p = .005), with males showing a higher prevalence (11.9%) than females (5.8%). Categorization in ADHD subtypes revealed that 2.5% of the participants could be typified as the primarily inattentive type (≥5 symptoms of the inattention items and <5 symptoms of the hyperactivity/impulsivity items), 2.8% as the primarily hyperactive/impulsive type (<5 symptoms of the inattention items and ≥5 symptoms of the hyperactivity/impulsivity items) and 2.9% as the combined type (≥5 symptoms of the inattention items as well as ≥5 symptoms of the hyperactivity/impulsivity items). These prevalences did only differ significantly between sexes for the inattentive subtype for which females had a lower prevalence (1.4%) than males (4.1%)  = 4.7, p = .031; hyperactivity/impulsivity: χ2 = 0.5, p = .472; combined: χ2 = 3.7, p = .056).For determination of people with subclinical ADHD, a selection of participants was made meeting the criteria for a subclinical DSM-5 diagnosis of ADHD by means of the ADHD Rating Scale . The criteria of a subclinical DSM-5 diagnosis were fulfilled if the participant scored in the clinical range on the retrospective as well as current items. Conforming to the scoring system by Kooij et al. , a partip < .001, η2 = .59) as well as childhood  = 169.6, p < .001, η2 = .61) with large effect sizes. This indicates that we successfully selected two extreme groups regarding self-reported ADHD symptoms. The matched groups did not differ in age (F(1113) = 0.00, p = .984), with a mean of 26.7 years ranging from 17 to 51 years. Both groups contained 32 males and 24 females. The groups did not differ either in their educational level  = 3.7, p = .451), their job status  = 0.3, p = .870) or their relationship status  = 9.0, p = .061).A control group was created by matching the 56 participants with subclinical ADHD to 56 participants of the remainder of the sample that had the same sex, the same student status  and similar age. The subclinical ADHD group reported significantly more ADHD symptoms than the control group in adulthood  = 161.0, The Dutch version of the ADHD DSM-IV rating scale (ARS) was used with items on current ADHD symptoms during the last 6 months and retrospective items on childhood ADHD symptoms below the age of 12 years   using the following formulas E = [EQ–M(EQ)/56] and S = [SQ-R–M(SQ-R)/150], i.e., the individual difference with the group mean was divided by the maximum score on the respective questionnaire. Brain types were calculated by computing the difference between E and S and by normalizing with the factor ½ as is appropriate for an axis rotation: D = [(S–E)/2]. D represents the continuous variable for brain type, in which a positive score indicates brain type S or extreme type S, a negative score indicates brain type E or extreme type E and a score close to zero indicates a balanced brain type (B).Based on the EQ and SQ-R, a person’s brain type can be computed, which is the standardized difference score of the SQ-R and EQ: D  and good validity; females achieve higher FQ scores than males, and patients with high-functioning autism achieve lowered FQ scores compared to both male and female controls (Baron-Cohen and Wheelwright A Dutch translation of the Friendship Questionnaire (FQ) was used, which is a 35-item self-report questionnaire measuring the quality of friendships  and sex  as independent variables. Potential differences between ADHD subtypes were explored by performing subgroup analyses with subclinical DSM-5 diagnoses of the combined, inattentive and hyperactive/impulsive type. Effect sizes  were calculated for all group comparisons to indicate the magnitude of the group differences.To estimate differences in social cognitive style and quality of friendships between participants with subclinical ADHD and the control group, univariate ANOVAs were performed on the total EQ score and its subscales , the total SQ-R score and D with n = 685, in order to explore to what extent current symptoms of ADHD, social cognitive style and the combination of these two predict a person’s quality of friendships. FQ score was entered as the dependent variable and the following variables were entered as predictors using the forward method: the ARS total score, the subscale scores of the EQ , the total SQ-R score, D and the interaction terms of the ARS total score and the social cognitive style scores . As sex differences in FQ scores have previously been documented  ARS total score with the SS subscale, which significantly predicted the FQ score, but explained less than 1% of variance in the model.Thus, on top of sex and EE, people with more systemizing scores and people with more ADHD symptoms combined with a low SS score report lesser quality of their friendships, but these account only for a very small amount of the variance in the model.This exploratory study on the relation between subclinical ADHD symptoms and self-reported social cognitive functioning is one of the first studies examining self-reported social cognitive style in adult ADHD. We demonstrated that adults with a subclinical DSM-5 ADHD diagnosis reported reduced emotional empathy and a more systemizing cognitive style compared to the control group and that this pattern appeared to be independent of sex and ADHD subtype. The reduced emotional empathy score of the subclinical ADHD group was, however, still within the normal range compared to normative data (above the 10th percentile), which might be explained by the fact that not all of the participants of the subclinical ADHD group would meet the criteria of a formal diagnosis of ADHD. Therefore, this study ought to be replicated in a clinical sample of adult patients with a formal ADHD diagnosis. Moreover, additional measures assessing various domains of social cognition should be included. We do, however, speculate that reduced emotional empathy in people with subclinical ADHD is in accordance with studies showing problems with affective social cognition in patients with ADHD  in our community sample revealed that the higher quality of friendships is best predicted by the female gender and by a stronger experience of emotional empathy. Female respondents with higher emotional empathy scores reported higher levels of social engagement, enjoyment and importance of friendships. The self-reported quality of friendships was not related to either ADHD symptoms or the combination of more ADHD symptoms and reduced self-reported social cognitive functioning. Even though our findings did not support a lower quality of friendships in subclinical ADHD, people with ADHD might be at higher risk of having a lower quality of friendships since the literature states that adults with clinical ADHD suffer from friendship problems, poorer social interactions and intimate relationships and loneliness  empathy and does not represent a typical ASD-like profile, which typically shows overall reduced empathy scores and increased systemizing scores  appears to be in line with previous studies on social cognitive functioning in adults with ADHD. Bora and Pantelis  stressedThis study presented with several limitations. First, social cognitive style was merely measured by self-report questionnaires which rely on a realistic self-perception. It is possible that people with a subclinical diagnosis of ADHD over- or underestimate their empathic and social skills. For example, several studies have shown that children, adolescents and adults with ADHD show a ‘positive illusory bias,’ as defined by ‘a self-enhancing discrepancy between self-reports of competence and external indices of competence, such as ratings by other informants  or objective measures of performance’  ADHD. As social cognitive functions of adults with ADHD remains a relatively underexposed research field, our study contributes to the scarce existing knowledge on this topic. Furthermore, all participants were assessed with well-validated self-report questionnaires. The fact that we found lower emotional empathy scores in a subclinical ADHD group points to the relevance of replication and extension of this study in clinical ADHD groups.Based on self-reported questionnaires in a subclinical, adult ADHD group, we found lower self-perceived emotional empathy scores, independent of sex and ADHD subtype. Self-perceived cognitive empathy and social skills were not diminished compared to the control group, which is in line with a recently published meta-analysis on social cognition in adult ADHD (Bora and Pantelis


Diagnostic guidelines recommend using a variety of methods to assess and diagnose ADHD. Applying subjective measures always incorporates risks such as informant biases or large differences between ratings obtained from diverse sources. Furthermore, it has been demonstrated that ratings and tests seem to assess somewhat different constructs. The use of objective measures might thus yield valuable information for diagnosing ADHD. This study aims at evaluating the role of objective measures when trying to distinguish between individuals with ADHD and controls. Our sample consisted of children (n = 60) and adults (n = 76) diagnosed with ADHD and matched controls who completed self- and observer ratings as well as objective tasks. Diagnosis was primarily based on clinical interviews. A popular pattern recognition approach, support vector machines, was used to predict the diagnosis.We observed relatively high accuracy of 79% (adults) and 78% (children) applying solely objective measures. Predicting an ADHD diagnosis using both subjective and objective measures exceeded the accuracy of objective measures for both adults (89.5%) and children (86.7%), with the subjective variables proving to be the most relevant.We argue that objective measures are more robust against rater bias and errors inherent in subjective measures and may be more replicable. Considering the high accuracy of objective measures only, we found in our study, we think that they should be incorporated in diagnostic procedures for assessing ADHD. Attention deficit/hyperactivity disorder (ADHD) is characterized by a combination of age-inappropriate levels of inattention, impulsive behavior and hyperactivity. Symptoms must become apparent before the age of 12 years and cause significant impairments in more than one setting, e.g., at school or work, or with family and peers ), and evobjective measures when trying to distinguish between individuals with ADHD and controls. We also aimed to investigate how objective measures are related to subjective measures by investigating how well we could discriminate between ADHD and controls when using the combination of these two types of measures. The combination of objective and subjective measures may provide additional information than objective measures alone as it has been argued that tests and ratings may capture at least partly different constructs )nstructs , 23 and The relative importance of individual variables towards a diagnosis of ADHD is an issue that has not been empirically examined, at least not in studies employing statistical methods that can handle numerous variables to make an objective prediction. Similarly, few studies focus on objective measurements of ADHD symptom levels rather than constructs (such as executive functioning deficits) that are known to be associated with ADHD.In Germany, where this study was conducted, a frequently used neuropsychological test is the test battery of attention for adolescents and adults  or for ©;  LOOCV procedure—which does not include the novel data) was used in the final prediction. This approach has been described in greater detail elsewhere . NotablyOur child datasets included age, gender, Conners-3 parent/teacher ratings, QbTest 6–12 and the KiTAP scores; the adult datasets age, gender, CAARS-L: S/O, QbTest+© and TAP. IQ and medication history were not included in the prediction for reasons as outlined above. Tables ©. Additionally, the Qb factor inattention correlated significantly positive with the inattention symptom scale of the CAARS observer scale as well as with the TAP variables reaction time and reaction time variance (RT SD). Finally, there were significant correlations between the number of omission errors in the TAP tasks and the ADHD and inattention symptom scales of the CAARS. Regarding the child sample, we also found positive correlations between the Qb impulsivity factor and the number of errors in the KiTAP tasks Go/Nogo and sustained attention. Furthermore, there were positive correlations between the Qb inattention factor and the reaction time and reaction time variance of the sustained attention task. In general, there were only few significant correlations between the subjective and the objective variables, a fact already shown in previous studies [As expected, we found significant negative correlations between IQ, the Conners’ symptom scale for inattention and the ADHD index as well as the Qb factors. Furthermore, there were significant positive correlations between corresponding variables of the different TAP/KiTAP tasks. Regarding the adult sample, the Qb factor for impulsivity correlated significantly positive with the number of errors of most of the TAP tasks, indicating that patients who produced a lot of errors in the TAP also scored high on the impulsivity factor of the Qb+ studies , 37.2 = 44.26, p < .0001). The majority of the variables relevant to the classification were selected from the CAARS scores. Many of the scores from the self-ratings were especially predictive, with each of the 51 variables selected in 36.20% of the predictions on average. Similarly, the observer-rated scores contained many predictive variables, with each variable selected in 20% of the cross-validated classifiers on average. This was expected, as symptom severity scores are likely to readily distinguish patients from controls.Using a linear SVM and feature selection on the adult dataset, we were able to predict an ADHD diagnosis with 89.5% accuracy . The following variables were used in over 85% of predictions: overall omission errors made at the subtest sustained attention in the TAP; QbTest+©: omission errors, error rate, normalized reaction time variance, normalized reaction time variance without outliers, and the ability of the patient to distinguish between target and non-target.When including only objective measures (the output from the QbTest+© and TAP tasks), we predicted an ADHD diagnosis with 79% accuracy . As in the adult study, the Conners’ scores proved to be the most predictive of an ADHD diagnosis. Only 12 parent-rated scores were entered into the classification procedure, and those variables were selected in 36.53% of the predictions on average. The Conners’ parent subscores relating to executive function, inattention DSM-IV ratings and the ADHD index were selected in all predictions, and the general inattention score was selected in 75% of the predictions. None of the variables taken from the KiTAP were selected in any of the predictions, while the 15 QbTest 6–12 variables entered into the classifier were selected in only 1.11% of the predictions on average.By applying the same technique used to predict diagnosis in the adult population to 30 children with ADHD and 30 controls, we were able to predict diagnosis with 86.7% accuracy . The following variables were used in over 98% of predictions: KiTAP: sustained attention—number of omission errors, GoNogo—median of reaction time and number of errors; QbTest 6–12: distance participant moved during testing, area covered by the patient during testing, micro movements exceeding 1 mm, complexity of movement-pattern, multiple pressing of the test button, reaction time variance without outliers, normalized reaction time variance without outliers, anticipatory, reactions < 150 ms that are considered accidental. All prediction results are summarized in Table When using only the output from the QbTest 6–12 and KiTAP tasks, it was possible to predict an ADHD diagnosis with 78% accuracy  followed by the observer-rated scores (selected on average in 20%). Variables of both the Qb+© variables omission errors, error rate, reaction time variance, and the participant’s ability to distinguish between target and non-target. This finding is in line with previous findings, as a review of 33 studies on the neuropsychology of adults with ADHD identified omission errors and reaction time variance as variables well able to discriminate between adults with ADHD and controls [© was indicative of overall impairment, adding key supplemental information. Another study demonstrated that the Qb+© is sensitive to medication effects, showing an improvement in 54% of patients who reported no changes in the subjective measure [Regarding the TAP, the variable omission errors from the subtest “sustained attention” was selected in more than 85% of the predictions; the same accounts for the Qb+controls . This iscontrols . Our fincontrols . It is ucontrols , ratingscontrols , when secontrols , 77), orcontrols . Recent controls  showed t measure .We were able to predict an ADHD diagnosis in children based on all of the variables with 86.7% accuracy. Here, no self-ratings were used, but the sub-scores “executive functioning”, “DSM IV inattention” and the “ADHD index” of the parent-ratings were selected in all predictions demonstrating their diagnostic value. The prediction using the objective measures did not produce as accurate a classifier as the combined objective and subjective measures in our child sample. However, predicting an ADHD diagnosis using only the objective measures was still significant with 78% accuracy.Similar to the adult sample, the variable omission errors of the subtest “sustained attention” of the KiTAP was selected in more than 98% of the predictions, as was the median of the reaction time and number of errors in the “Go/NoGo” subtest. This is in line with previous research showing that children with ADHD commit both more omission errors and commission errors than healthy controls –82. LookWe found significant negative correlations between IQ, the Conners’ symptoms scale of inattention and the ADHD index, two of the KiTAP variables indicative for inattention (reaction time variance and omission errors) and the Qb factors. This is not surprising as the children with ADHD had lower IQ, which is known to be typical for this population , 57. TheAccording to the DSM-criteria  for ADHDAnother limitation of our study is the relatively small number of participants in each group . As we aimed to be able to make reliable claims regarding the diagnostic accuracy of the instruments assessed, we focused on having gender- and age-matched groups. This resulted in relatively small group sizes, but the total number of participants (N = 136) can be regarded as satisfactory.Future research should preferably include a clinical control sample, as it is highly relevant for clinicians to be able to distinguish between patients with ADHD and those exhibiting similar symptoms due to another underlying disorder .In conclusion, we took a sophisticated statistical approach in this study to examine the diagnostic contributions of various measures assessing ADHD and to assess their classification accuracy. The present findings are highly relevant for clinicians, and can help to improve the workup for diagnosing ADHD. Our investigation’s findings demonstrate that when using both subjective and objective measures, an ADHD diagnosis can be accurately predicted with high sensitivity  and specificity . Whilst the combination of objective and subjective measures produced more accurate results than the classification based on objective measures only, the latter was still highly satisfactory and removes a potential source of error. The core symptom of hyperactivity is captured especially well in children via objective measures. Considering the evidence that ratings and tests seem to assess at least partly different constructs , objecti


Individuals born with low birth weight (LBW) risk cardiometabolic complications later in life. However the impact of LBW on general health status and male reproductive function has been scantly analysed. We investigated the clinical and seminal impact of different birth weights (BW) in white-European men presenting for primary couple’s infertility. Demographic, clinical, and laboratory data from 827 primary infertile men were compared with those of 373 consecutive fertile men. Patients with BW ≤2500, 2500–4200, and ≥4200gr were classified as having LBW, normal (NBW), and high BW (HBW), respectively. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Testicular volume was assessed with a Prader orchidometer. Semen analysis values were assessed based on 2010 WHO reference criteria. Descriptive statistics and regression models tested associations between semen parameters, clinical characteristics and BW categories. LBW, NBW and HBW were found in 71 (8.6%), 651 (78.7%) and 105 (12.7%) infertile men, respectively. LBW was more frequent in infertile patients than fertile men (p = 0.002). Infertile patients with LBW had a higher rate of comorbidities (p = 0.003), lower mean testicular volume (p = 0.007), higher FSH (p = 0.02) and lower tT levels (p = 0.04) compared to other BW groups. Higher rates of asthenozoospermia (p = 0.02) and teratozoospermia (p = 0.03) were also found in LBW men. At logistic regression models, LBW was univariably associated with pathologic progressive motility (p≤0.02) and pathologic sperm morphology (p<0.005). At multivariable logistic regression analysis, LBW achieved independent predictor status for both lower sperm motility and pathologic sperm morphology . Only LBW independently predicted higher CCI values (p<0.001). In conclusion, we found that LBW was more frequent in infertile than in fertile men. Infertile individuals with LBW showed a higher rate of comorbidities and significantly worse clinical, endocrine and semen parameters compared to other BW groups. The Devertility . Furtherertility –10. Recerm count . Conversrm count –15, evenrm count ,17. Likerm count –21.These conflicting observations, along with the lack of previous clinical evidence considering the potential impact of LBW on general health status and overall male reproductive function prompted us to investigate the eventual role of different categories of BW in male infertility, specifically assessing (i) prevalence of LBW, (ii) its correlations with clinical characteristics, and (iii) its impact on semen and hormonal parameters in a homogeneous cohort of white-European men presenting for primary couple’s infertility. Moreover, clinical and BW of primary infertile men were compared with those of a homogeneous cohort of age-comparable fertile men.The analyses of this cross-sectional study were based on a sample of 850 consecutive white-European men assessed at a single academic centre for primary couple’s infertility  between January 2012 and September 2014. According to the World Health Organisation (WHO) criteria, infertility was defined as not conceiving a pregnancy after at least 12 months of unprotected intercourse regardless of whether or not a pregnancy ultimately occurred . PrimaryPatients were assessed with a thorough medical history including age and comorbidities. Comorbidities were scored with the Charlson Comorbidity Index (CCI) . We usedWe also collected clinical data from 373 fertile white-European men who had fathered at least one child, spontaneously conceived, with a time to pregnancy within 12 months. These men were recruited via their partners who had been new and expectant mothers in our department of Obstetrics and Gynaecology. For the specific purpose of the study we collected only clinical data from the fertile group of individuals .am and 11 am after an overnight fast. In all cases, fasting glucose levels were measured via a glucose oxidase method . Total cholesterol, HDL-C, and triglyceride levels were measured with the automated enzymatic colorimetric method . Impaired HDL-C values were considered if HDL-C < 40 mg/dl. Hypercholesterolemia  and hypertriglyceridemia (triglycerides ≥150 mg/dl) were assessed [2) were measured using a heterogeneous competitive magnetic separation assay . Inhibin B (InhB) and anti-Müllerian hormone (AMH) were measured with an enzyme-linked immunosorbent assay (Beckman Coulter AMH Gen II ELISA). Total testosterone (tT) levels were measured via a direct chemiluminescence immunoassay , and sex hormone-binding globulin (SHBG) levels were measured via a solid-phase chemiluminescent immunometric assay on Immulite 2000 . Hypogonadism was defined as tT less than 3 ng/ml [Venous blood samples were drawn from each infertile patient between 7 assessed . Follicl 3 ng/ml . The samData collection was carried out following the principles outlined in the Declaration of Helsinki; after approval of the IRCCS San Raffaele Hospital’s Ethical Committee, all patients signed an informed consent agreeing to supply their own anonymous data for this and future studies.Data are presented as means . The statistical significance of differences in means and proportions was tested with the one-way analysis of variance (ANOVA) and Pearson chi-square test, respectively. A 95% confidence interval was estimated for the association of categorical parameters. Exploratory analyses were initially applied to all variables; variables were retained for analysis when deemed clinically significant to the results. Logistic regression univariable analysis (UVA) and multivariable analysis (MVA) tested the associations between clinical and laboratory predictors  and pathologic semen parameters as defined by the WHO 2010 criteria . FurtherAs a whole, LBW was found in 8.6% of patients and 3.2% of fertile individuals ; mean BWConversely, patients with LBW shared a heavier burden of comorbidities (p = 0.003) and had a lower mean testicular volume (p = 0.007) compared to patients in the other groups, although there was no different prevalence of varicocele among the three patient groups divided according to BW. Moreover, LBW group showed a higher prevalence of impaired HDL-C values (p = 0.04) as compared with other groups; in contrast, no differences were observed in terms of impaired values of cholesterol or triglycerides among the groups.2, SHBG, PRL, and TSH values among groups ; both LBW (p<0.005) and FSH values (p = 0.003) were also significantly associated with pathologic sperm morphology. At logistic MVA, only FSH levels achieved independent predictor status for pathologic sperm concentration (p<0.001). Lower BW (p<0.04) achieved independent predictor status for lower sperm motility; both LBW and FSH values were independent predictors of pathologic sperm morphology . Only LBW significantly predicted higher CCI values (p<0.001).Tables We assessed the prevalence along with the clinical and seminal impact of different categories of BW in a relatively large cohort of white-European men seeking medical attention for the first time for primary couple’s infertility. When compared with fertile men, infertile individuals showed a lower mean BW and a higher proportion of LBW. Moreover, infertile men had a higher mean BMI value and reported a greater proportion of clinically significant comorbidities (namely CCI≥1), as compared to fertile individuals. More specifically, we found that infertile men born with LBW had reduced sperm motility and reduced normal sperm morphology compared to NBW and HBW men. Individuals with LBW also showed lower tT levels but higher FSH values, compared with those in the other groups. Moreover LBW patients reported a higher rate of health significant comorbidities and reduced left testicular volume. As a whole, the current findings provide new evidence in support of the hypothesis that BW has an impact on gonadal function in postnatal life.et al. for instance reported that SGA individuals have a pituitary-gonadal axis that tends toward hypogonadism [Our interest was fuelled by existing controversies regarding the relationship between the developmental environment and postnatal reproductive function in men –15. In tgonadism . A positgonadism . Moreovegonadism ,9. In cogonadism ,15. Overgonadism ,30.et al. showed that subfertile men had a LBW while men with normal semen analysis reported a NBW [et al. found that BW was associated with sperm DNA fragmentation and inversely correlated with total sperm count [Few studies have investigated the impact of BW on seminal parameters of fertile and subfertile individuals. Francois ed a NBW . Howeverrm count , highligrm count –16. In oTo the best of our knowledge, this is the first naturalistic, cross-sectional, observational study in which a relatively large cohort of infertile individuals underwent a comprehensive clinical, endocrine and seminal evaluation. Of importance, we found a statistically significant association between BW and impaired seminal parameters. Although BW represents only a proxy of the intrauterine factors acting on the development of the gonadal system, we speculate that it may have an influence on semen quality in adulthood.et al. reported, instead, that individuals born with HBW had an increased risk of being obese in later life, being affected by diseases of the heart and circulation, but were not at an increased risk for the development of type 2 diabetes mellitus [From a clinical standpoint, higher BW is generally an indication of a more favourable intrauterine environment, although some exceptions have been identified, thus including the macrosomia exhibited by infants of diabetic women . On the mellitus . Our finet al. showed that men with azoospermia have an increased risk of subsequently developing cancer, suggesting a possible common aetiology between azoospermia and cancer development [et al. found a strong association between a decreased general health status (coded by the CCI) and impaired gonadal function in infertile men [et al. reported a relationship between medical comorbidities and male semen production [Of clinical relevance, men with LBW reported a higher prevalence of health significant comorbidities, depicted by the CCI, as compared with the other groups. Despite the known association between the weight at birth and cardiometabolic diseases , no one elopment . Moreoveelopment . Recentltile men . Likewisoduction . As we fOne major limitation of this study is related to the fact current that data come from a hospital-based centre assessing primary infertile men only, thus highlighting the importance of an external validation of the current results. Second, although the study provides original and novel findings, our relatively small cohort of white-European men could limit the meaningfulness of the findings themselves. In this context, though the rigorous homogeneity of the sample in racial terms may represent strength, to ensure the generalizability of the results, a larger population-based survey should be employed to validate the current findings. Third, we have no data on the seminal characteristics of the fertile population, so investigating the impact of BW in the healthy individuals was not possible. Finally, although all enrolled patients reported being born at term their exact gestational age was actually not available in the birth records to confirm these reports.These cross-sectional analyses in a relatively large homogeneous white-European cohort of primary infertile men  showed novel evidence of a higher prevalence of LBW as compared with a comparable cohort of fertile individuals. Moreover, LBW not only is associated with qualitative alterations of the semen, but it also associated with a decreased overall health status.S1 Dataset(XLS)Click here for additional data file.


The Weiss Functional Impairment Rating Scale-Parent Form (WFIRS-P) is a 50-item scale that assesses functional impairment on six clinically relevant domains typically affected in attention-deficit/hyperactivity disorder (ADHD). As functional impairment is central to ADHD, the WFIRS-P offers potential as a tool for assessing functional impairment in ADHD. These analyses were designed to examine the overall performance of WFIRS-P in differentiating ADHD and non-ADHD cases using receiver operating characteristics (ROC) analysis. This is the first attempt to empirically determine the level of functional impairment that differentiates ADHD children from normal controls.n = 476) and non-ADHD controls (n = 202). ROC analysis evaluated the ability of WFIRS-P to discriminate between ADHD and non-ADHD, and identified a WFIRS-P cut-off score that optimises correct classification. Data were analysed for the complete sample, for males versus females and for participants in two age groups (5–12 versus 13–19 years).This observational study comprised 5–19-year-olds with physician-diagnosed ADHD (Area under the curve (AUC) was 0.91  for the overall WFIRS-P score, suggesting highly accurate classification of ADHD distinct from non-ADHD. Sensitivity (0.83) and specificity (0.85) were maximal for a mean overall WFIRS-P score of 0.65, suggesting that this is an appropriate threshold for differentiation. DeLong’s test found no significant differences in AUCs for males versus females or 5–12 versus 13–19 years, suggesting that WFIRS-P is an accurate classifier of ADHD across gender and age.When assessing function, WFIRS-P appears to provide a simple and effective basis for differentiating between individuals with/without ADHD in terms of functional impairment.Disease-specific applications of QOL research. Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioural disorder in children and adolescents, characterised by inattention, motor hyperactivity, and impulsivity , 2. AccuUnderstanding the full impact of ADHD should in part be based on the severity of any functional impairment. Therefore, measurement of the impact of ADHD should be based on the accurate evaluation and recording of symptoms, and functional impairment, using valid, reliable, and sensitive rating scales . Such scThe Weiss Functional Impairment Rating Scale-Parent Form (WFIRS-P) is a 50-item scale designed to evaluate the extent to which an individual’s ability to function is impaired by any emotional or behavioural problems . The scaThe objectives of this study were, therefore, to examine the overall performance of the WFIRS-P in differentiating ADHD and non-ADHD cases using receiver operating characteristics (ROC) analysis, and identify a test score that optimises the correct classification of cases. The performance of the WFIRS-P was evaluated for both the overall and the individual domain scores, and compared across male and female subjects and those of different ages, to determine whether diagnostic accuracy was maintained across gender and age. Establishment of a WFIRS-P cut-off score that differentiates normal from abnormal functioning may also be a useful first step in establishing a rigorous empirical definition of functional impairment. Further research might then also establish empirical definitions for acceptable functioning in ADHD.This was an observational study comprising a sample of parents of individuals aged 5–19 years who reported that they had been diagnosed with ADHD, and a similar group of parents of non-ADHD controls who were healthy young people of the same age as the ADHD sample. Participants were recruited from the following countries: UK (138), US (128), Germany (140), Spain (64), Canada (69), France (39), Italy (50), and Netherlands (50). No formal sample size estimation was conducted, and these represent convenience samples. Recruitment specialists identified potential participants through advertising, patient advocacy groups and through treating physicians. All data in the study were collected from parents of individuals with ADHD, and it was the parents who consented to take part in the study. This study was approved by an Independent Review Board [Essex Institutional Review Board (A2190)]. No additional review was sought in each country, because this was a non-interventional survey of parents of young people with ADHD—rather than the actual patients themselves. The agency that we worked with for participant recruitment reviewed the study and agreed that it met their professional standards for survey research. All participants provided informed consent.The data were collected by a specialist recruitment agency who identified the parents of children with ADHD. The data were collected through a postal survey. Parents received study packs through the post and were asked to complete and return them. Participants who had agreed to take part were followed up if they had not returned the forms. The study packs included the WFIRS-P along with demographic forms. Each individual’s ADHD status was recorded based on self-report by the parent or caregiver. The control group was recruited to provide a comparison group broadly matched for age.The WFIRS-P is a 50-item scale that requires parents to rate the impact of their child’s emotional or behavioural problems in the previous month on six separate domains: (A) Family (ten items); (B) School and learning (ten items); (C) Life skills (ten items); (D) Child’s self-concept (three items); (E) Social activities (seven items); and (F) Risky activities (ten items). Each item is rated on a four-point scale from 0  to 3 (‘very often or very much’) or rated as ‘not applicable’. The mean of all scored items for each domain was computed. Each domain score, therefore, has a minimum–maximum range of 0–3. A single overall WFIRS-P score was also calculated as the average of the six domain scores.ROC curve analysis provides a means to evaluate an instrument’s ability to successfully differentiate cases from non-cases for a variety of cut-off scores. In the case of the WFIRS-P, a threshold score can be applied, with scores above this threshold used to classify cases and scores below this threshold used to classify non-cases. ROC analysis allows a comprehensive evaluation of the overall discriminatory performance of the test by plotting sensitivity and specificity rates for the entire range of scores, thus enabling an optimal cut-off score that represents the highest overall level of sensitivity and specificity to be identified. In this study, non-parametric ROC was used due to a slight floor effect (positive skew) in WFIRS-P scores observed for controls. Overall WFIRS-P test scores were analysed, along with each scale domain score. Data were analysed for the complete sample, as well as for males compared with females and for participants in two age groups (5–12 versus 13–19 years).An area under the curve (AUC) statistic was calculated to provide a single summary measure of test performance using the non-parametric trapezoidal method. Higher AUC values indicate better overall test sensitivity and specificity, with 1.0 representing perfect discrimination of cases and non-cases, and 0.5 representing chance classification. DeLong’s test for paired ROC curves was used to compare AUC values across WFIRS-P domains, with DeLong’s test for independent groups used to compare AUC values across gender and age group subsamples .J values indicating greater combined sensitivity and specificity [J value can be used as an optimal overall classification threshold for the study sample. All analyses were conducted using the statistical package R version 3.1.2 [An optimal WFIRS-P threshold score for case differentiation was derived using Youden’s Index, a commonly used statistic that reflects overall test performance, with higher Youden’s cificity , with boon 3.1.2 .The participant demographics and WFIRS-P scores are presented in Table Sensitivity and specificity values were calculated across the entire range of overall WFIRS-P total scores and are displayed in Fig. J was calculated for every test score. A J value of 0 indicates poor overall sensitivity and specificity  for a specific cut-off score, whereas a value of 1 indicates 100% sensitivity and specificity. The computed J was highest (J = 0.68) for the WFIRS-P cut-off value of 0.65, indicating this to be the optimal cut-off value for maximising discrimination of ADHD and non-ADHD cases . Given the apparent classification superiority of these domains, the performance of A and B domain scales was compared with the overall WFIRS-P scores. Results provided some evidence that the AUC of the overall WFIRS-P may be greater than that of domains A (p = 0.002) and B (p = 0.052). However, the difference in actual AUC values between the overall total scale (0.91) and domains A (0.90) and B (0.88) is minimal and suggests that overall performance is similar across scales in terms of clinical relevance.To examine the classification performance of individual WFIRS-P domains, ROC analysis was repeated for the six subscales. The AUCs and confidence intervals for the ROC curves of all six domains, along with optimal thresholds and associated sensitivity and specificity, are shown in Table D = 0.09–1.58; p = 0.93–0.11). Similarly, ROC analysis and DeLong’s test results comparing WFIRS-P scores for participants aged 5–12 years with those aged 13–19 years revealed no significant differences for either the overall or domain scales  and School and learning (B) domains were associated with especially high levels of overall classification, differences between domain scores were minimal and unlikely to be clinically important. Although it would be injudicious to consider a cut-off value from a single statistical index as a definitive threshold, results from the current study provide guidance for consideration of a generalised WFIRS-P cut-off value of around 0.65 for which sensitivity and specificity are likely to be high. Although the AUC indicated an ‘outstanding’ classification according to the standard guidelines , it woulSeveral limitations of the study should be noted. First, the study sample contained comparatively fewer females than males. Although the total number of females in both ADHD and control groups was adequate for analysis, replication of the current results  is ideally required before extrapolating to the wider population. In addition, the optimal classification cut-off score we obtained here for children may be different for adults when a self-report version of the scale is used or, given that diagnostic criteria may vary slightly across regions when used in a different country. As such, future studies could examine the impact of these factors on both the overall classification performance and the identification of an appropriate cut-off score. Third, although the WFIRS-P did demonstrate accurate discrimination of functional impairment between ADHD and non-ADHD, it may be that alternative scoring methods may provide even better classification. For example, the mean value for the scale may sometimes fail to capture functional impairment that is driven by a few salient and severely impaired items , and this could suggest an alternative scoring procedure that accounts for this and could offer superior performance. For example, apart from overall mean score, children with either one symptom that is severe (3) or two symptoms that are moderate (2) within a domain could be considered functionally impaired in that domain. DSM-IV diagnosis of ADHD required that a child shows functional impairment in at least two settings or domains. The DSM-5 Disability Group recommend use of the WHODAS 2.0 which is based on the International Classification of Functioning, Disability and Health . The WHOThe control group was recruited with the same age range as the ADHD group, which meant that the two groups were broadly matched in terms of mean age but were not matched on an individual basis. A key limitation of this study is that verification of diagnosis  were not available, which meant that we relied on self-reported diagnosis of ADHD. Although we have no strong reason to believe that this would introduce any systematic bias, this could potentially affect the precision of the sensitivity and specificity estimates of the scale in differentiating between cases and controls.In this study data set, detailed information regarding disease severity was not available, so it was not possible to consider this in any analysis. Finally, and importantly, while the WFIRS-P appeared to accurately discriminate functional impairment between ADHD and non-ADHD controls, further work would be needed to examine the ability of the WFIRS-P to differentiate how and to what extent the functional impairment identified on this measure is specific to ADHD.This study empirically examines the threshold that differentiates functional impairment in ADHD versus non-ADHD individuals. Current practice guidelines and diagnostic criteria have established that diagnosis and measurement of outcome must address both symptom criteria and functional impairment. We have good symptom rating scales and empirically based cut-off scores that define a generally agreed upon cut-off score for symptoms. This study has established that a mean score of 0.65 on the WFIRS-P reliably differentiates individuals with ADHD who are functionally impaired from controls. As well as confirming that ADHD is associated with considerable functional impairment compared with normal controls across several domains, the current findings also endorse the ability of the WFIRS-P to provide accurate classification of functional impairment in ADHD across gender and for both children and adolescents, and provide a suggested general cut-off score to help optimise classification. These results support the potential for the WFIRS-P as a quick and easily administered assessment of functional impairment in ADHD, which could be used to prompt further, more detailed, clinical investigation.


Problems in inhibitory control are regarded in Psychology as a key problem associated with attention-deficit/hyperactivity disorder (ADHD). They, however, might not be primary deficits, but instead a consequence of inattention. At least two components have been identified and dissociated in studies in regards to inhibitory control: interference suppression, responsible for controlling interference by resisting irrelevant or misleading information, and response inhibition, referring to withholding a response or overriding an ongoing behavior. Poor error awareness and self-monitoring undermine an individual’s ability to inhibit inadequate responses and change course of action. In non-social contexts, an individual depends on his own cognition to regulate his mistakes. In social contexts, however, there are many social cues that should help that individual to perceive his mistakes and inhibit inadequate responses. The processes involved in perceiving and interpreting those social cues are arguably part of a self-protection system (SPS). Individuals with ADHD not only present impulsive behaviors in social contexts, but also have difficulty perceiving their inadequate responses and overriding ongoing actions toward more appropriate ones. In this paper, we discuss that those difficulties are arguably a consequence of an impaired SPS, due to visual attention deficits and subsequent failure in perceiving and recognizing accurately negative emotions in facial expressions, especially anger. We discuss evidence that children with ADHD exhibit problems in a series of components involved in the activation of that system and advocate that the inability to identify the anger expressed by others, and thus, not experiencing the fear response that should follow, is, ultimately, what prevents them from inhibiting the ongoing inappropriate behavior, since a potential threat is not registered. Getting involved in high-risk situations, such as reckless driving, could also be a consequence of not registering a threat and thus, not experiencing fear. The attention-deficit/hyperactivity disorder (ADHD) is traditionally characterized by intense and persistent difficulty in regulating attention and/or hyperactivity behaviors and/or impulsivity, thus producing a significant distress in many areas of the affected individual’s life . AccordiRecent studies estimate that the prevalence of ADHD ranges from 6 to 7% among children and adolescents, 5% among young adults , and 3% Since ADHD is considered a lifespan disorder, the impairments vary across age. In childhood, ADHD is related to learning disabilities , frequenvice versa , which enhances error awareness and inhibition of inadequate social behaviors. We argue that an impaired self-protection system (ISPS) is ultimately what causes perseverance of improper behaviors related to impulsivity/hyperactivity in individuals with ADHD.Human communication is multimodal, occurring through different channels of communication, such as facial and corporal expressions, speech, and prosody . The corIndividuals with ADHD have difficulty recognizing emotions in facial expressions , 45, an According to a meta-analysis, deficits in recognition of anger and fear in facial expressions have been observed in children with ADHD . Highly A neuroimaging study analyzed hemodynamic responses to expressions of happiness and anger in boys with ADHD, and it concluded that they have a lower hemodynamic response when facing the expression of anger . Young aAnger is one of the seven universal facial expressions of emotion  and, theEvolutionary social psychology describes the mechanisms to detect any possible threat and properly respond to it –65. The An expression of anger is evaluated by that system as a possible signal of violent intent, and it leads to a fear response . At the An expression of anger can be a social sign of rejection of the other , disapprAn angry face can be tracked much faster in a crowd of neutral faces, in comparison to a happy face –82. ThisChildren in kindergarten seem to achieve a better performance in Go/No-Go tasks when they experience negative emotions, probably because those emotions lead to a more focused and attentive behavior, oriented toward problem-solving and reducing the chance of committing mistakes . StudiesPhysiological studies indicate that the hypothalamic–pituitary–axis (HPA) plays a fundamental role in stress response by promoting behavioral and peripheral changes capable of maximizing the body’s ability to adjust its homeostasis and increasing the chances of survival through the release of glucocorticoids, mainly cortisol . It has It was reported that cortisol administration may improve inhibitory control in healthy adults on a Go/No-Go task . In anotChildren with ADHD seem to present lower levels of diurnal cortisol, in comparison to those without the condition, and treatment with atomoxetine may help normalize these levels . Also, cSome authors emphasize the need to consider other processes for a more comprehensive understanding of ADHD, highlighting the importance of those related to emotion and social cognition . In an aChildren with ADHD have visual attention deficits , which cTheory of Mind refers to the natural ability to assertively infer other people’s beliefs and desires, and to use this information to make assumptions and predict their behavior , 105. SeAs mentioned before, Anger Recognition is the first step to activating the SPS, and Theory of Mind is responsible for properly interpreting that emotion . If therA recent study partially corroborates this hypothesis by establishing that patients with ADHD, in addition to their difficulty recognizing anger, show a reduced ability to inhibit responses in the emotional Go/No-Go task, and this difficulty is more pronounced when the stimulus is a face expressing anger . This hyAdditionally, there are other processes indirectly involved in the activation of the SPS that seem to be impaired in patients with ADHD. Hereupon, we will present them and, subsequently, make an effort to unravel the possible connections between them and the other variables discussed so far.“Mimicry” can be defined as the tendency to imitate facial, vocal, or postural expressions of the person who we are interacting with . There aFacial mimicry favors the emotional experience in itself, which facilitates the recognition of the emotion of the other . It is aThere is evidence that the corrugator supercilli muscle, fundamental to creating facial expressions of negative emotions, such as anger and fear, displays electrical activity after only 100 ms of the perception of a mistake. That reaction is associated to the concept of “error awareness,” defined as the tendency to slow down responses after perceiving a committed mistake or a received punishment, increasing self-monitoring and proceeding more cautiously in order not to commit further mistakes .Some neuroimaging studies have already identified brain circuits involved in facial mimicry . SpecifiConsidering that one of the main regions involved in the inhibitory control is also responsible for anger mimicry, we could assume that individuals with ADHD present difficulties in facial mimicry, which would hamper their ability to simulate and infer emotions of others. But, so far, only one study has investigated the relationship between ADHD and facial mimicry , and it The process of observing, identifying, discriminating, and evaluating one’s emotions is called Emotional Awareness . In contAlexithymia has also been associated to impairments in the processing of threat-related facial expressions, emotion recognition , and to There is evidence that children with ADHD show low levels of emotional self-awareness, and it is associated with externalizing behavior, in this case, opposition and challenging behavior in response to some perceived provocation . AlexithAs shown in Figure We continued by explaining how social disapproval of one’s inadequate behavior is usually expressed as an angry expression and how visual attention is important in order to perceive that expression. That perception should be interpreted by the individual using Theory of Mind, in order to recognize that the perceived stimulus is an angry face, and that it is directed to him or her. Facial mimicry will help in the emotion recognition process, by internally simulating the observed expression.Subsequently, anger recognition should be registered as a potential threat to the individual, allowing the SPS to take action, triggering a fear response. Emotional awareness, underpinned by social cues, will be a key to accurately experience and interpret those emotions, internally and externally. Ultimately, the SPS would lead that individual to inhibit his own behavior, discontinuing the action that had caused social disapproval in the first place. An adequate Theory of Mind and emotional awareness would be critical for interpreting the whole situation and establishing a cause and effect relationship, as well as regulating one’s own emotions and evaluating the appropriate outcome.All of that represents a whole cognitive circuitry that starts with visual attention and ends with inhibitory control. In individuals with ADHD, however, all of those functions seem to be impaired, impeding the SPS to be set in motion. As a consequence, social behavior is not properly regulated, resulting in social exclusion and worsening the patient’s condition.We argue that the link between the ISPS and the deficits in inhibitory control, specifically the “response inhibition” component, may be explained by reduced error awareness, since the ability to perceive their own mistakes is fundamental to individuals, in order to control their own behavior . Being aAccording to a recent meta-analysis, patients with ADHD do not present adequate “post-error slowing,” which is the natural reduction in response times after identifying one’s error. In other words, these patients do not present the tendency to be cautious in order to avoid committing further mistakes . AnotherWe argue that this reduced error awareness, specifically observed in social contexts in which a child with ADHD does not understand that he or she is behaving inadequately, happens because of problems in the SPS.faux pas or an improper response due to not understanding a given social rule. Either way, an individual should perceive his mistake and override his action, even trying to compensate for it.It is important to note that an inadequate social response might not only be related to an impulsive/hyperactive behavior but might also be a simply The SPS concept as proposed by evolutionary psychologists specifically designates anger recognition as the stimulus that put that system in motion. However, we theorize that in non-social contexts, other stimuli could be registered as a potential threat, triggering a fear response and leading to response inhibition as well. Other researchers have proposed the risk-as-feelings hypothesis, discussing that emotional reactions to risky situations often account more to decision-making than cognitive assessment of those risks, driving behavioral responses even if it means resisting cognitive interpretation of consequences . It is pInterestingly, pharmacological treatment for those patients, particularly the use of methylphenidate, seems to improve Theory of Mind , 144 andWe must clarify that we do not intend to cover all the complexity of ADHD with the hypothesis here presented. It was outlined based on research and evidence available so far in literature. Therefore, we recognize and emphasize the need for empirical data that might support our hypothesis.It is important to note that inhibitory control varies significantly depending on the context , which iAmong the several aspects to be further investigated, the “Anger Superiority Effect” has already been analyzed in several psychiatric disorders, such as in Asperger Syndrome , generalIn addition to this, the degree of dependence between visual attention and emotional perception is still controversial , and so,As for the deficits in relation to Theory of Mind, most studies do not clarify whether they are related to the affective dimension (theorizing about the affections of others) or to the cognitive dimension (theorizing about thoughts and intentions of others) of that construct, as recently described . This tyThere is also a need to clarify whether children with ADHD present a subjective response of fear when facing images of anger expression, which could demonstrate a more specific impairment of the SPS. It would also be important to analyze if there is evidence of alexithymia in patients with ADHD specifically related to fear. Furthermore, it would be interesting to verify if the induction of fear could affect inhibitory control in patients with ADHD. In regards to facial mimicry, studies involving children of other age groups would be important in order to assess if there are any alterations involving anger mimicry or not.We should investigate if the difficulty in recognizing anger in ADHD patients is restricted to facial expression, since anger can be communicated also through body muscle contraction , postureClinically, it will be important to investigate whether psychological interventions focused on training recognition and adequate response to anger expressions would significantly improve inhibitory control. It creates a promising field to further investigate ADHD and possibly characterize differences and similarities between gender, age, and subtype of ADHD. Even though our hypothesis has been developed to approach ADHD deficits, it is possible that it might apply to other psychiatric disorders. For instance, response inhibition deficits have been also observed in patients with schizophrenia , 156, asSince we are presenting a novel hypothesis, alternative explanations should be assessed experimentally. Some core deficits in ADHD, as the primary attentional deficit, sensation seeking behavior, and general impulsiveness traits could also explain the lack of ability in perceiving inappropriate social responses. Future studies controlling for inattention and inhibition problems should be carried out using experimental design. The emotional Go/No-Go task  may be uOur hypothesis might also lead to a better understanding of the inhibitory control mechanism in typical individuals. Individual differences in regards to emotion recognition have been observed in healthy individuals, both in children  and adulThe purpose of this paper was to present and discuss a plausible theoretical explanation for the problems in inhibitory control, specifically in the “response inhibition” component, observed in patients with ADHD, addressing them as a consequence of an ISPS which does not function properly because of primary visual attention deficits.We have made an effort to take social, clinical psychology, and evolutionary perspectives into account. Empirical investigation, however, is necessary in order to find evidence that supports the ISPS hypothesis. Ultimately, we hope we have contributed to the efforts of better understanding ADHD and connecting the knowledge gathered so far by the scientific community.TC carried out the literature review and elaborated the initial review that gave rise to the basic structure of the hypothesis. SR contributed to the theoretical basis and discussion of the proposal, besides the semantic and grammatical revision. DM guided the article, contributing to the theoretical basis and discussion of the proposal. AS contributed to the theoretical basis and dicussion of the proposal. LM-D guided the article, contributed to the theoretical basis and discussion of the proposal.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.