Research has shown that those with attention-deficit/hyperactivity disorder (ADHD) have an increased risk for addiction disorders like alcoholism and substance abuse. What is less clear is the mechanism(s) whereby ADHD gives rise to increased engagement in addictive behaviors, and whether there are sex differences in the ADHD-addiction propensity. Both ADHD and addictions have also been associated with personality traits such as impulsivity, reward seeking, anxiousness, and negative affect. In this study, we tested a moderator-mediation model, which predicted that both sex and ADHD-symptom status would make independent contributions to the variance in personality risk and in addictive behaviors, with males, and those with diagnosed ADHD, scoring higher on both dependent variables. Our model also predicted that the effect of sex and ADHD-symptom status on addictive behaviors would be via the mediating or intervening influence of personality-risk factors.n = 83) and a low-symptom group (n = 84).A community-based sample of young men and women took part in the study. Among these individuals, 46 had received a lifetime diagnosis of ADHD. The non-diagnosed participants were dichotomized into a high-ADHD-symptom group (We found that a high-risk personality profile may, in part, account for the relationship between ADHD symptomatology and the use/abuse of a broad range of addictive behaviors. However, we found no sex differences in personality risk for addiction or in the use of addictive behaviors; nor did sex moderate the relationships we assessed.While ADHD status showed a strong relationship with both dependent variables in the model, we found no difference between those who had been diagnosed with ADHD and treated with stimulants, and their high-symptom non-diagnosed/non-treated counterparts. These results add support to claims that the treatment of ADHD with stimulant medication neither protects nor fosters the risk for substance abuse disorders. Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable ≈70%) neuropsychiatric disorder with typical onset in childhood . Further0% neuropThe ADHD-drug use/abuse link is also evident from the reverse perspective. It has been estimated that up to 50% of adolescents and adults with substance abuse disorders have a lifetime diagnosis of ADHD . For exaIn a recent 15-year, longitudinal, population-based ADHD study, the prevalence of substance abuse/dependence was substantially higher (≈31%), however, for nicotine than for other drugs like alcohol, cannabis, and cocaine . It alsoStimulant medication for ADHD continues to be the first-line treatment for this disorder in most clinical settings, despite lingering concerns about its potential for abuse and whether it may sensitize individuals to later problematic substance use . Drugs lIn an early meta-analysis of six stimulant-treatment outcome studies, Wilens and colleagues  concludeonly in boys use are well-documented, there has been little information about mechanisms that might foster this connection. One approach has been to examine the influence of personality traits associated with both ADHD and substance users in the general population. In this regard, the very limited ADHD research has focused largely on facets of impulsivity and their association with alcohol consumption in this clinical cohort . Other Results of recent longitudinal research have also shown that the development of internalizing problems such as depression and anxiety – largely through peer rejection – mediates the relationship between ADHD symptoms and risk for substance use and abuse . Indeed,In the quest to better understand the mechanisms linking ADHD symptoms to addictive behaviors, no mediational research has examined whether stimulant-medication treatment for ADHD affects the hypothesized associations among the variables of interest. Moreover, the possible role of sex differences in moderating these associations is untested. To address these issues, the current study has employed a case-double-control design. Examining undiagnosed individuals with high-ADHD symptoms in the general community, as well as stimulant-treated clinical cases of ADHD, in relation to addictive behaviors removes the potential confounding effects of medication status on outcome.In this study, a moderated-mediation analysis was used to test our prediction that a composite index of personality risk – including impulsivity traits, reward sensitivity, and anxiety proneness – mediates the relationship between ADHD symptomatology on the one hand, and a general tendency toward engaging in addictive behaviors on the other. We also predicted that sex would moderate these relationships with males showing higher scores on all the measured variables compared to females  and women (n = 116) between the ages of 17 and 32 years were recruited from the community of a large Canadian university . Mean ages (and SD) of the participants were 22.5 (3.3) and 22.2 (3.3) years, for males and females, respectively. Among these individuals, 46  had received a diagnosis of ADHD, and were either currently being treated with stimulant medications or had been in the past. The prescribed medications were Concerta, Ritalin, Vyvanse, Adderall, and Dexedrine. Participants were required to be fluent in written and spoken English and to have lived in North America since childhood. Exclusion criteria included a current diagnosis of an addiction disorder and a current or lifetime diagnosis of a psychotic disorder using an abbreviated (non-patient) version of the structured clinical interview for DSM-IV (SCID).A sample of young men  and a low-symptom group  based on a median split of their scores on the well-validated Connors Adult ADHD Rating Scale (CAARS)  stimulant medication as part of their treatment protocol. If stimulants were taken, the participant was asked for the length and dates of the treatment, and for the name of the prescribed medication. Approximately half of the ADHD group was still on stimulant medication at the time of study participation, while the other half had a prior history of pharmacotherapy with stimulants, but was no longer receiving treatment at the time of recruitment. The non-diagnosed participants were dichotomized into a high-ADHD-symptom group ( (CAARS) . The selImpulsivity was assessed by the well-validated 30-item Barratt Impulsivity Scale (BIS)  of the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ)  of the Eysenck Personality Questionnaire-Revised (EPQ-R)  le (BIS) , which i (SPSRQ) . This sc (SPSRQ) , 41. The (EPQ-R) . This sc (EPQ-R) . In addi (EPQ-R) , this sc (EPQ-R) , patholo (EPQ-R) , and tho (EPQ-R) , 48. Ther between 0.33 and 0.41; all p-values <0.0001). A composite score was therefore calculated using principal component analysis, as described in the Section “The three variables described above were moderately correlated, as expected  and the ADHD (p = 0.008) groups, who did not differ from each other. Although statistically significant in our sample, an age difference of 1–2 years in young adulthood was not considered clinically relevant in the context of our research. With respect to the classification variable for the control groups (viz. symptom scores as assessed by the CAARS), the ADHD group had significantly higher scores than the low-symptom group (p < 0.0001). Surprisingly, there was no difference between the ADHD groups and the high-symptom control group (p = 0.456).Table In order to create a latent variable reflecting personality risk, a composite score was calculated for the three personality variables  using a principal component analysis. The extracted component accounted for 58% of the variance in the three personality scales, and all three loaded strongly on this factor (loadings ranged from 0.73 to 0.79).Post hoc comparisons using the least significant difference (LSD) test indicated that the low-symptom group had significantly lower personality-risk scores than the ADHD group (p < 0.0001) and the high-symptom group (p < 0.0001), which did not differ from each other (p = 0.634). Neither the main effect for sex nor the AHDH status × sex interaction was statistically significant. Table Path A was tested using a 3 (ADHD status) × 2 (Sex) ANOVA with personality risk as the dependent variable. There was a significant main effect for ADHD status. Path B was tested by regressing addictive behaviors on the personality-risk factor score, and results indicated a significant positive association between the two variables (see Table Post hoc comparisons using the LSD test again indicated that the low-symptom group had significantly lower scores on the addictive-behaviors variable than the ADHD group (p < 0.0001) and the high-symptom group (p = 0.001), which did not differ from each other (p = 0.348). Neither the main effect for sex nor the AHDH status × sex interaction was statistically significant. Table Path C (without the mediating variable) was tested using a 3 (ADHD status) × 2 (sex) ANOVA with addictive behaviors as the dependent variable. There was a significant main effect for ADHD status. r p = 0.38. NeithePath C′ was tested by repeating the analysis described in Section “In the final step, general proclivity for addictive behaviors, we also expect that some readers may be interested in the statistical outcome for each individual addictive behavior. The following provides a summary of these results, and should be viewed as information supplementary to the original hypothesis-driven analyses. Table F ratios were statistical significant for ADHD status and for sex . However, the main-effects interaction term did not reach statistical significance. Results of the univariate results are provided below.Although we selected an aggregate index in this study to reflect a p = 0.01) and alcohol (p = 0.01) consumption compared to females, while females were more prone to compulsive shopping (p = 0.001).For these three variables, there were no main effects for ADHD status. However, males had a higher frequency of caffeine . Post hoc comparisons using the LSD procedure indicated that for recreation drug use, the ADHD group had significantly higher scores than both the low- and the high-symptom groups (p < 0.0001 in each case), who did not differ significantly from each other. With respect to nicotine, similar results were found with the ADHD group having higher scores than the high-symptom (p = 0.026) and the low-symptom (p < 0.0001) groups, who again were not different from each other.In contrast, for these two addictive behaviors there were no main effects for sex. There were, however, significant main effects for ADHD status  and sex . Not surprisingly, woman had higher scores on food binging than men, while the reverse was found for sexual activity. Concerning food binging, the high-symptom group had more elevated scores than either the low-symptom (p = 0.001) or the ADHD groups (p = 0.027), who did not differ from each other. And finally, the low-symptom group had reduced scores on the sexual-activity variable compared to the high-symptom (p = 0.037) and the ADHD (p = 0.004) groups, who were not significantly different from each other.For these two variables, there was a significant additive effect of ADHD status . Indeed, this possibility gains credibility since most of the ADHD participants in our study were recruited from the student body of a local university. On the other hand, a recent survey of childhood impairments in those with and without ADHD – based on retrospective adult recall – found that while the ADHD group reported more school difficulties compared to controls, there were no differences in their respective levels of educational attainment . Such daIt was of considerable interest to find no differences in the magnitude of the personality-risk index between those with AHDH and the high-symptom group, although again both had significantly higher scores than the low-symptom group. The composite personality variable – created for the current study as a marker of risk for addictive behaviors – is not only validated empirically by our results but also complements previous research in this area. For instance, both novelty seeking and harm avoidance were significantly greater in a large group of patients with opiate addiction and/or alcohol dependence compared to normal controls . IndividContrary to expectations, and after controlling for ADHD status in our analyses, there were no male–female differences in personality risk, nor in the use of addictive behaviors; neither did sex moderate the relationships tested in our mediation model. Concerning the addictive-behaviors variable – and in light of our findings that individual differences in risk were not sex-specific – it may be that sex differences were washed out because we operationalized addictive behaviors as an aggregate index of several activities, both substance and non-substance related. Some addictive behaviors, like compulsive buying  and bingIn conclusion, strengths of this study are the inclusion of a non-diagnosed and non-treated group of young adults with high-ADHD symptom severity equivalent to the group of clinically diagnosed ADHD participants. In addition, we also included a low-symptom control group, thereby providing a double control for the clinical cases. Our focus on both mediating and moderating factors in connection to the ADHD-addictive behaviors link is another strong point of this research. The use of a composite dependent-variable index of addictive behaviors also provided a more comprehensive approach than one which examined each addictive activity separately . This strategy is particularly relevant since preferences for specific addictive activities are known to vary across sociocultural groups –61. In aHowever, despite the merits of our current research, it is also important to address the limitations of the study. Foremost is the fact that the ADHD participants comprised two distinct sub-groups – those who were currently on stimulant medication and those who had been, but were no longer, taking these drugs. While our data indicated that the two groups did not differ on the variables included in this study, these analyses may have been under-powered by virtue of relatively small sample sizes. Another constraint of the study is that the associations we observed were based on cross-sectional data, thereby limiting our ability to infer directional relationships between symptoms and behaviors. While it is intuitive, for example, to suppose that ADHD symptoms contribute to the use and abuse of addictive behaviors, it is also known that chronic use of addictive substances/activities can foster some of the symptoms that define ADHD such as poor impulse control . Only loTo summarize, we found that a high-risk personality profile may, in part, account for the relationship between ADHD symptomatology and the use/abuse of a broad range of addictive behaviors. We also found no evidence that current or past treatment of ADHD symptoms with stimulant medication increases the probability of engaging in potentially addictive activities. While there is good evidence that ADHD is more prevalent in males than in females , we founThe 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.


Investigators at Departments of Child Neurology, Neuroscience, Biostatistics, Marmara University, Istanbul, Turkey studied the parameters for prediction of epileptiform abnormalities in the EEG of 148 children diagnosed with ADHD, according to DSM-IV criteria, aged between 6 and 13 years . Wake and sleep EEGs lasting about one hour were obtained in 89.2% patients and a WISC-R in 100%. Investigators at Departments of Child Neurology, Neuroscience, Biostatistics, Marmara University, Istanbul, Turkey studied the parameters for prediction of epileptiform abnormalities in the EEG of 148 children diagnosed with ADHD, according to DSM-IV criteria, aged between 6 and 13 years . Wake and sleep EEGs lasting about one hour were obtained in 89.2% patients and a WISC-R in 100%. The coexistence of speech sound disorder and higher Digit Span test performance predicted the occurrence of epileptiform discharges in the EEG. The prevalence of epileptiform abnormalities was 26.4%; they were frequently localized in the frontal (41%) and centrotemporal (28.2%) regions. Speech sound disorder co-occurrence (64%) with rolandic spikes suggests that the pathophysiology of epileptiform abnormalities in ADHD might be genetically determined. [COMMENTARY. The utility of the EEG in a child presenting with ADHD is a frequent and sometimes hotly debated subject. The American Academy of Pediatrics (AAP), in their 2000 clinical practice guideline for diagnosis of ADHD . A seconWhereas the studies in the 1990s, in agreement with the AAP guideline, are not supportive of the routine use of the EEG in diagnosis of ADHD, subsequent research regarding the utility of the EEG in the management of patients with ADHD shows that an increased susceptibility to epilepsy is sufficiently strong to warrant investigation. Of 624 records (94.5% sleep-deprived) of nonepileptic children evaluated for ADHD in our clinic and laboratory, 163 (26.8%) were abnormal, 42.9% only focal spikes, chiefly central, frontal, and temporal .


Searching, defined for the purpose of the present study as the displacement of an individual to locate resources, is a fundamental behavior of all mobile organisms. In humans this behavior underlies many aspects of everyday life, involving cognitive processes such as sustained attention, memory and inhibition. We explored the performance of 36 treatment-free children diagnosed with attention-deficit hyperactivity disorder (ADHD) and 132 children from a control school sample on the ecologically based ball-search field task (BSFT), which required them to locate and collect golf balls in a large outdoor area. Children of both groups enjoyed the task and were motivated to participate in it. However, performance showed that ADHD-diagnosed subjects were significantly less efficient in their searching. We suggest that the BSFT provides a promising basis for developing more complex ecologically-derived tests that might help to better identify particular cognitive processes and impairments associated with ADHD. Search behavior, defined in the context of the present study as whole body displacements made with the aim of finding a particular resource or reaching a particular goal under conditions of uncertainty, is a basic phenomenon of fundamental ecological relevance1Searching, following the definition provided above, involves a wide range of cognitive skills. In order to find something one must have some idea of what it looks like, avoid places that were already visited or leave places where the likelihood of finding the object is low, perhaps have an ordered or systematic strategy – try nearby places before going further and wasting valuable time and energy and possibly increasing the chance of experiencing an unpleasant or harmful event. Motivation, experience and other factors also contribute to a successful search. Certainly finding the object(s) is one criterion to end a searching process, but costs such as time and energy represent central aspects influencing the decision-making processes for an efficient search.It is not difficult to imagine how cognitive inefficiency can be detrimental to a person’s life. For instance, attention-deficit hyperactivity disorder (ADHD) is a chronic neurodevelopmental condition characterized by atypical levels of inattention, hyperactivity and impulsivity that impact negatively on everyday functioning5The understanding of psychiatric disorders such as ADHD are substantially aided by neuropsychological tests evaluating cognitive performance89et al.Among some of the ingenious tests designed to meet such needs, we can mention the large-scale foraging task used by Pellicano Here we propose an ecologically relevant test to evaluate children with and without a diagnosis of ADHD that can be applied across a wide range of ages. The test is based on previous work on searching behavior in natural and semi-natural contexts15The aim of the present study was to compare the performance of children with ADHD, given their lower sustained attention, with an unselected control sample in a searching task involving large open spaces.We tested children from 5+ to 12+ years of age, of both sexes and without evident motor disturbances. They were recruited from two settings, a children’s psychiatric hospital and a primary school. The school sample was balanced for age and gender, whereas 81% of the participants from the hospital were male.n = 36, mean age 8.9 yrs, SD 1.7, range = 6.6–12.8, 28 males) were outpatients at the Hospital Psiquiátrico Infantil Juan N. Navarro in Mexico City, a public hospital specialized in the diagnosis and treatment of psychiatric disorders in children and adolescents. The inclusion criteria for participation were a diagnosis of ADHD based on a structured diagnostic interview with the parents or legal guardians 18never, sometimes, often). Exclusion criteria included only comorbidity with psychosis or pervasive developmental disorders.Participants  were an unselected sample of pupils at an elementary school in Mexico City.Participants , these were responded to using standard pre-constructed answers that avoided specifics (“You can do it in whichever way you want”).After answering a short verbal questionnaire providing their name, age, and school class, children were brought individually to the starting point on the soccer field . At the Two raters (PI and a research assistant) observed the child’s behavior and used a GPS-synchronized chronometer to record on a map of the cone array the time at which each cone was lifted Hospital subjects’ performance on the Tower of London task (ToLo)t-tests, or for nonparametric frequency data, Mann-Whitney U tests to compare the performance at different ages of the hospital and school groups. Pearson partial correlations, controlling for age, were performed for the hospital sample to evaluate the relationship between symptom severity, IQ and BSFT descriptors. To compare the hospital subjects’ performance on standardized neuropsychological tests against normative values we used a one-sample Student t test and quantified the effect size using Cohen’s d.We used Student We used a two-sample test for equality of proportions22p < 0.05.Statistical analyses and data visualization were performed using the statistical software Rt-test: t = 1.08, df = 63.92, p = 0.28). All subjects engaged readily in the task, and most ran rather than walked around the field. Among the children that met the inclusion criteria, none was excluded or refused to participate in the task. Even the youngest had no difficulty understanding the instructions as shown by the generally good performance at all ages (see below). No correlations were found between the performance of hospital subjects on the BSFT and symptom severity. However, positive significant correlations were found between IQ and time taken to finish the search task (r = −0.48) and efficiency of collections .There was not a significant difference in age between the school and the hospital participants , or in the percentage of children who finished in under 4 minutes . However, the percentage of hospital subjects who made one or more mistakes was significantly larger . Their performance on the ToLo was significantly worse only on number of rule violations . Despite the BSFT showing a certain capacity for discrimination between samples, and the use of commonly used tasks to evaluate some aspects of cognitive function in ADHD subjects, no correlation was found between any of the performance measures of the BSFT, ToLo and BRIEF scores or between the ToLo and BRIEF scores.Children at the hospital were rated as having poor executive performance by their parents or guardians. The values for all items of the BRIEF were significantly different from the population mean, with large size effects .


This study reviewed the use of the Strengths and Weaknesses ofAttention-Deficit/Hyperactivity-symptoms and Normal-behaviors (SWAN) rating scale indiagnostic and evolutive approaches to attention deficit hyperactivity disorder(ADHD) and in correlational studies of the disorder. A review of articles publishedin indexed journals from electronic databases was conducted and 61 articles on theSWAN scale were analyzed. From these, 27 were selected to a) examine use of SWAN inresearch on attention disorders and b) verify evidence of its usefulness in the areasof genetics, neuropsychology, diagnostics, psychiatric comorbidities, neuroimaging,pharmacotherapy, and to examine its statistical reliability and validity in studiesof diverse populations. This review of articles indicated a growing use of the SWANscale for diagnostic purposes, for therapy, and in research on areas other than ADHD,especially when compared with other reliable scales. Use of the scale in ADHDdiagnosis requires further statistical testing to define its psychometricproperties. Attention deficit hyperactivity disorder (ADHD) affects 5–6% of the child and adolescentage 6 to 12 years) population 2 years p and haveCurrently, the heritable genetic, clinical, and physiological profiles of ADHD have beenincreasingly defined by standards and references based on scientific, statistical, andneuroimaging studies, as research has focused on the search for endophenotypes andmarkers that can further delineate physiopathological and diagnostic methods –7. ThegThere are existing scales that have already been standardized and validated to evaluateADHD in children and adolescents –12, for The purpose of this review was to locate citations containing scientific evidence thatthe SWAN scale can be used to describe symptoms, evaluate individuals in relation to thenormal distribution of behaviors, evaluate possible treatment, and is applicable togenome-wide association studies (GWAS) and neuropsychological studies on ADHD. Weconducted a literature review and classified 28 articles into seven areas of interest:genetics, neuropsychology, diagnostics, psychiatric comorbidities, neuroimaging,pharmacotherapy, and statistical reliability and validity.Diagnostic and Statistical Manual of Mental Disorders, 4thedition (DSM-IV)  . DiffereVan der Sluis et al. , in theiIn observations and analyses of attention behaviors or motor activity, as with any otherbehavioral problem in the general population, responses are compared to the normaldistribution; on this continuum, ADHD is defined as the lower extreme ,15,16. SIn this context, Swanson et al. ,21 demonThe SWAN scale was created by Swanson et al. and compThis literature review searched electronic databases for relevant internationalscientific journals, specialized books, notes from academic debates, and notes fromresearch teams.The following initial criteria were used: 1) articles published from 2000  to 2014; 2)digitally published studies in online databases ;3) notes from academic debates and notes from research teams published in newspapers andmagazines.The following keywords were used for the electronic search: ADHD and SWAN scale, SWANand genetics, SWAN and neuroscience, and neuropsychological assessment. A total of 61scientific studies that mentioned SWAN in ADHD research were analyzed from this period,out of which 27 were selected and meticulously assessed and analyzed to determine theuse of the scale in ADHD studies associated with the following subjects: diagnosticapproaches to ADHD symptoms, genetic studies (between twins and siblings of ADHDcarriers), the evolution of medical interventions, studies related to neuropsychologicalaspects of ADHD, studies on the reliability and validity of statistics, neuroimaging,and the interface between ADHD and neuropsychiatric comorbidities. All of these articlesare summarized in The literature review was structured around seven fields of ADHD research in which theSWAN scale was used, and examined studies in the following areas: diagnostic evaluationand symptoms, genetics, the evolution of therapeutics and pharmacotherapeutics, aspectsof neuropsychology, statistical reliability and validity, comorbidities, andneuroimaging.Overall, the articles examined indicate that the scale permits the analysis of attentionskills in large normal population samples because it provides - by its dimensionalprofile - common signs of selective, sustained, and executive attention in items thatreflect normal behavior observed in the general population. This aspect makes itpossible to compare control groups with groups showing deviations from average scores onattentional items disproportionate to a normal population. Three articles showed thatthe distribution of these abilities in the populations researched resembled a Gaussiancurve , a distrThese articles also suggest that the SWAN scale can detect negative signs and traces ofADHD in a population when compared to previously published and validated scales, such asthe Disruptive Behavior Rating Scale (DBRS) and the ADS-IV   as it calatrophilin 3 gene  10/10-repeatallele . In addin 3 gene  and DAT1ne  in neuropsychiatricdisorders, or in studies of complex traits and conditions like ADHD that showgene-environment interactions, have permitted improvements in the use of phenotypicinformation, allowing comparison of allele frequency between cases and controls and morepower to detect statistically significant gene sequences. The development ofquestionnaires and referential scales, in turn, strengthens statistical power . Seven aOnly one study used the SWAN scale to correlate ADHD and developmental coordinationdisorder scores ; this stOne study  used SWAThis article reviewed studies that applied the SWAN scale to various fields, fromstatistical analysis to clinical use in ADHD diagnostic and therapeutic processes. Itsuse in evaluating phenotypic attentional characteristics and their variations could helpADHD researchers to correlate genetic measures with phenotypic ADHD traits. The scalehas also been useful in the quantitative assessment of pharmacological treatment, thecomparison of results across a range of statistically consolidated scales, and thecorrelation of ratings with neuropsychological data.vs medication) is valuable in generating new scientific researchstrategies in the ADHD field, especially those that search for more biological markersand those that aim to clarify physiopathological mechanisms.Crosschecking data from the scale with allelic repetitions in large population samples,active functional standards of neuroimaging, and pharmaceutical evolution , and the relative lack of specialists in most countriesto adequately evaluate children and adolescents. The SWAN scale could contribute to thework of professionals in tracking additional problems in childhood and could improveboth diagnostic work and studies on the ADHD spectrum.


Both distractions  and attention-deficit/hyperactivity disorder (ADHD) are serious risk factors for traffic crashes and injuries. However, it is still unknown if ADHD (a chronic condition) modifies the effect of distractions (irregular hazards) on traffic crashes. The objective of this study was to assess the effects of distractions and ADHD on traffic crash responsibility.A responsibility case-control study was conducted in the adult emergency department of Bordeaux University Hospital, France. Subjects were recruited among drivers injured in a motor vehicle crash between April 2010 and August 2011. Responsibility levels were estimated using a standardized method. Frequencies of exposures were compared between drivers responsible and drivers not responsible for the crash. Independent risk factors were identified using a multivariate logistic regression including test interactions between distractions and ADHD.A total of 777 subjects were included in the analysis. Factors associated with responsibility were distraction induced by an external event (adjusted OR (aOR)  = 1.47; 95% confidence interval (CI) [1.06–2.05]), distraction induced by an internal thought  and ADHD (aOR = 2.18 CI: [1.22–3.88]). The combined effect of ADHD and external distractions was strongly associated with responsibility for the crash (aOR = 5.79 CI: [2.06–16.32]). Interaction assessment showed that the attributable proportion due to the interaction among participants with both exposures was 68%.Adults with ADHD are a population at higher risk of being responsible for a road traffic crash when exposed to external distractions. This result reinforces the need to diagnose adult ADHD and to include road safety awareness messages delivered by the physician. Developing advanced driver assistance systems devoted to the management of attention lapses is also increasingly relevant for these drivers. Injuries due to traffic accidents will become the fifth leading cause of death by 2030 if preventive interventions are not implemented quickly . Whereas rising motorization in newly industrialized countries increases the worldwide population at risk for traffic crash, high income countries have faced a plateauing of the number of lives saved Among human factors related to traffic crashes, attention issues have been largely ignored by road safety research. Yet, while driving, the driver is submitted to several stimuli causing distractions to deal with. This may degrade the driver's performance in his main task and increase the risk of accidents . Interestingly, distractions  and attention-deficit/hyperactivity disorder (ADHD) have been associated with traffic crashes Internal distraction includes all signals from the body which divert the driver's attention from the driving task. It comprises mind wandering (i.e. thoughts unrelated to the task at hand) Attention-deficit hyperactivity disorder (ADHD) is a lifelong disorder which has also been associated with traffic crashes Overall, both distractions and ADHD impact driving. Whereas distractions occur irregularly and randomly, ADHD is a chronic condition characterizing the individual. We hypothesized that ADHD would modify the effect of distractions on traffic crashes. The objective of the study was to assess the effect of distractions  and ADHD on responsibility for traffic crash and test the interactions between these two risk factors.We performed a comparative study of responsibility in a population of patients involved in injurious road traffic crashes. Its principle was to compare the frequency of exposures  and confounders between drivers responsible for the crash (cases) and drivers not responsible for the crash (controls). The study was conducted in the adult emergency department of the Bordeaux University Hospital (France), which serves urban and rural populations of an area comprising more than 1.4 million people. Patients were recruited from April 2010 to August 2011. Data were collected by trained research interviewers through direct interviews using a standardized questionnaire including questions about the crash, the patient's characteristics and the potentially distracting tasks or events at the time of the crash. To preserve intimacy and improve report reliability, the part of the questionnaire with psychiatric screening tools was self-reported. All participants were informed and signed a written consent form. This study was approved by the French data protection authority  and the regional ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre Mer III).Patients were eligible for study inclusion if they had been admitted to the emergency department in the previous 72 hours for injury linked to a road traffic crash, were aged 18 or older, were drivers in the crash and were able to answer the interviewer . We assessed 1,436 patients for eligibility. Of these, 368 were excluded for ineligibility . This resulted in 1068 eligible patients. Of these, 57 refused to participate and a further 56 were excluded from the analysis because of insufficient data. Of the 955 drivers included, 178 did not answer the screening tools for psychiatric disorders. The final sample for analysis comprised 777 participants (73% of the eligible drivers). There was no significant difference between the respondent group and the non-respondent group with respect to responsibility in the crash .Responsibility levels in the crash were determined by a standardized method adapted from the quantitative Robertson and Drummer crash responsibility instrument Notably, this method of determining the driver's crash responsibility was compared with an independent expert responsibility evaluation, achieving fair agreement with a kappa of 0.71. The method takes into consideration 6 different mitigating factors considered to reduce driver responsibility: road environment, vehicle-related factors, traffic conditions, type of accident, traffic rule obedience and difficulty of the driving task. The adapted method we used has been described elsewhere When interviewed, patients were asked to describe distracting events and activities that occurred just before the crash  that led to the crash), from a list of potential distracting events and activities including: listening to the radio, cell phone use, navigation system use, having a conversation with passengers, eating, drinking, smoking, picking up an object, being distracted by an event outside the vehicle,…. The external distraction variable was then coded as a dichotomous variable: presence of external distraction (when there is at least one distraction reported) vs absence of external distraction.To assess mind wandering, patients were asked to describe their thought content just before the crash. To reduce memory bias and halo effect, they were given two opportunities to report their thoughts during the interview. Two researchers (CG and EL) examined and recoded each verbal reporting of thoughts until a consensus was found. Each thought was classified in one of the following categories: thought unrelated to the driving task or to the immediate sensory input, thought related to the driving task, no thought or no memory of any thought. To capture the intensity of the thought, the participant filled in a numerical scale (0–10) answering the question: “How much did the thought disrupt/distract you?” We then dichotomized the score (slightly disrupting/distracting 0–4 vs highly disrupting/distracting 5–10). Mind wandering was then coded as a dichotomous variable: internal distraction (ID) (mind wandering with highly distracting content unrelated to the driving task or to the immediate sensory input) vs no ID (mind wandering with little disrupting/distracting content unrelated to the driving task or to the immediate sensory input or no mind wandering reported).Potential confounders included patient's characteristics , crash characteristics , and self-reported psychotropic medicine use in the preceding week Patients were also asked how many hours they had slept during the previous 24 hours. They were considered as sleep deprived if they reported sleeping less than six hours. Emotional valence was evaluated with the self-assessment manikin (SAM) tool to characterize the driver's emotional valence state just before the crash We investigated three psychiatric dimensions using screening tools included in a self-administered questionnaire: ADHD symptoms, depressive disorders and anxiety disorders. These two last disorders were assessed as potential cofounders since ADHD is frequently associated with anxiety disorders, mood disorders and earlier onset of major depression The Achenbach System of Empirically Based Assessment (ASEBA) was used to screen for depressive disorders and anxiety disorders Participants were asked to report any current use of psychotropic medications from a list of psychiatric disorders, impairments and symptoms .Participants of the study sample were compared with the group of those excluded because they did not respond to the psychiatric disorders screening part of the questionnaire. Univariate and multivariate analyses  were conducted to determine associations between exposures, potential confounders and the driver's responsibility for a road traffic crash (responsible versus not responsible). Significant variables  were included in a multivariate logistic regression model. We then performed a manual stepwise backward logistic regression to select the variables in the final model used below to assess interaction between distraction and ADHD. To determine the extent to which ADHD modified associations between distractions and responsibility, we evaluated interaction on an additive scale. We assessed departures from additive effects as described by Rothman and colleagues when considering interaction, particularly in the public health field ++−OR+ −−OR− ++1 and AP =  RERI/OR++ (where OR designates odds ratio and the subscripts represent the presence or absence of each of the two risk factors). Bootstrapped confidence intervals were derived via 1,000 bootstrap replications of the original data. Confidence intervals were used to interpret interactions: RERI = 0 or AP = 0 means no interaction (exact additive affect); RERI>0 or AP>0 means positive interaction (beyond additive effect); RERI<0 or AP<0 means negative interaction (antagonism).RERI  =  OR6], AP = 0.16; 95%CI [−6.88–0.99])  were classified as controls and 358 (46.1%) as cases. 8–0.99]) .Among the 777 subjects included in the analysis, only 1 participant declared to use ADHD medication. Additional sensitivity analysis was performed and the results remained consistent when this participant was not included.Participants who had symptoms of ADHD, and those exposed to external/internal distractions were significantly more likely to be responsible for a road crash after adjustment for a range of potential confounders. Assessment of interaction showed a higher risk of being responsible when exposed to both external distraction and ADHD. The proportion of risk that is attributable to the interaction for those who were exposed to both ADHD and external distraction was 68%. These results are consistent with the increased risk of road crashes described in patients with ADHD. We can hypothesize that the effect of external distraction on the risk of being responsible for a road accident was higher in participants with ADHD compared with controls because of greater difficulty in managing the dual task situation. The process of managing the dual task involves the subject's ability to allocate attention flexibly between the tasks to be performed, an ability which can be affected by working memory impairment. Hence, the interaction between ADHD and external distraction could be related to the frequent working memory impairments in ADHD In our sample, only 1 participant declared to use ADHD medication. This is consistent with the fact that ADHD is currently underdiagnosed and treated in France and many European countries To our knowledge, there is no study of the interactions between distractions and ADHD, except for driving simulator studies This study has limitations which should be taken into account when interpreting its results. It includes subjective evaluation of both impairments and distraction exposures. The assessment of psychiatric disorders was not based on clinical diagnosis. Reassuringly, the ASRS-V1.1 has performed well in studies, shows good internal consistency, and good concordance with clinical diagnosis (area under the receiver operator curve 0.90) ADHD and external distraction are known risk factors for traffic crashes. The interaction assessed on an additive scale highlighted the impact of the combination of these two factors, a result with potential consequences as regard to prevention. This suggests potential public health benefits of ADHD screening. It is estimated that 2.5% of adults have ADHD, though many remain undiagnosed


The aim of this study was to assess the role of protective factors as mediators and/or moderators of the relationship between coexisting emotional and conduct problems and quality of life (QoL) among adolescents with attention-deficit/hyperactivity disorder (ADHD).The sample consisted of 194 adolescents with ADHD. Participants completed measures of individual competencies, family cohesion and social support, and QoL. Coexisting emotional and conduct problems were assessed using the Strength and Difficulties Questionnaire.Individual competencies and social support mediated the association between emotional and conduct problems and QoL. Family cohesion was associated with both emotional and conduct problems. No moderating effects of protective factors and coexisting problems were found.The assessment of individual competencies, social resources, and family cohesion may identify potential treatment goals for adolescents with ADHD and coexisting problems, and may contribute to improvements in QoL. Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous and composite disorder  that is Protective factors include both individual and environmental factors, and can be measured . These fCoexisting emotional and conduct problems are risk factors for an unfavorable outcome for adolescents with ADHD -7,22. WeQoL is a multidimensional concept and has various definitions ; neverthFor children and adolescents with ADHD, medical treatment is one of the major options to decrease ADHD symptoms and improve psychosocial functioning and QoL ,28-30. HPrevious research has focused on the direct relationships between psychopathology and QoL ,13. Howen = 49), leaving 194 participants in the present study : 87 girls and 107 boys.This study was part of The Health Survey performed by the Department of Child and Adolescent Psychiatry (CAP) at St. Olav’s University Hospital in Norway. This was a cross-sectional study of a defined clinical population. The catchment area was a county in Norway with 303,664 inhabitants, which includes urban and rural areas. The Department of CAP at the University Hospital covers all inhabitants in the county. The inclusion criteria were as follows: referred adolescents, age between 13 and 18 years, and presence of at least one attendance to the clinic between February 15, 2009 and February 15, 2011. Exclusion criteria were as follows: major difficulties in answering the questionnaire because of psychiatric state, cognitive dysfunctions, or lack of sufficient language skills. Emergency patients were invited to take part once stabilized. Among the 1,648 eligible and invited adolescents, 717 (43.5%) participated in the CAP survey. This survey and the representativeness of the sample have been described in detail previously . Of the Newly referred patients and patients who were already enrolled in the CAP clinic received oral and written invitations to participate in the study at first attendance after commencement of the project. The participating adolescents responded to an electronic questionnaire and data were collected from clinical charts. The ADHD rating scale was collected from the period of assessment prior to the initiation of medical treatment. Parents also responded to a questionnaire with items related to educational level.The parents of the participants completed a demographic form with information about age, sex, and socioeconomic status (SES). The highest educational level of parents on an 8-point Hollingshead scale was used to estimate SES .International Statistical Classification of Diseases and Related Health Problems (10th revision (ICD-10) . Standardized factor loadings are presented in Table Confirmatory factor analyses using items from the three subscales of the READ were conducted using our sample of ADHD patients (χ2(524) = 846.541, p = 0.000. The chi-squared/df-ratio was 1.62, which is commonly regarded as acceptable , with a significant chi-squared value, ceptable .A model analyzing the direct effect of coexisting problems on QoL was developed . A higher level of Hyperactivity/Inattention was associated with decreased QoL when adjusted for all variables included in the final path model (β = 0.143). Increased Age was associated with decreased QoL (β = 0.120), similar to that observed in the direct effect model.The final path model, which also included indirect effects of protective factors and medicated/unmedicated adolescents, is shown in Figure p = 0.644), of the effect of Emotional Problems on QoL , or of Hyperactivity/Inattention on QoL .Our analyses showed no interaction between coexisting problems  and protective factors  and no effect on QoL. For example, Individual Competencies was not a moderator of the effect of Conduct Problems on QoL (β = –0.034, The aim of this study was to assess the role of protective factors as mediators and moderators of the relationship between coexisting emotional problems and conduct problems and QoL among adolescents with ADHD. The results, based on self-reports, showed that protective factors mediated the association between emotional and conduct problems and QoL, even after adjusting for prescribed medication. Individual Competencies was the strongest mediator of the relationship between coexisting emotional problems and QoL. Furthermore, we found no significant interactions between coexisting factors and individual competencies, which indicates that there were no moderators.The major finding of this study was that individual competencies, which include structured style, social competence, and personal competence, were the strongest mediators of the relationship between emotional problems and QoL among adolescents with ADHD. These results suggest that adolescents with ADHD and a better structured style, social competence, and personal competence are more protected from coexisting emotional problems, and that these factors are associated with a better QoL. Executive function impairments among children with ADHD are heterogeneous ,56. The Our second finding was that social resources mediated the relationship between both emotional and conduct problems and QoL. Peer difficulties represent a significant area of impairment for adolescents with ADHD ,68. Our Another finding was the association between coexisting emotional and conduct problems and family cohesion. In a previous study, we found that coexisting problems had an impact on family functioning . Better Finally, adolescents with ADHD who received medical treatment had fewer conduct problems, indicating a positive effect of medication on conduct problems, which is consistent with previous work . ConversICD-10 diagnoses rather than on standardized semistructured child psychiatric interviews. Interrater reliability scores were not available; however, all diagnoses were established by an experienced child and adolescent psychiatrist or a clinical psychologist, and were based on standard national and international guidelines. Furthermore, the mean scores of the ADHD-RS were in the same range as those reported by other studies, including those of Norwegian clinical samples of adolescents with ADHD [The findings of the present study were limited by a low response rate, which could have led to imprecise results. Nevertheless, the reason for referral did not differ from the population of patients treated in the clinic during the study period. Another limitation was that the results were based only on self-reports. Previous studies have found that children with ADHD have a positive illusory bias and perceive their level of competence inaccurately ,83. Goodith ADHD ,86.The current study provided new information regarding the role of protective factors in the relationship between ADHD and coexisting emotional and conduct problems, and regarding the impact of these factors on QoL. Individual competencies, family cohesion, and social resources may reduce emotional problems and behavioral problems and improve QoL among adolescents with ADHD and among medicated individuals. The assessment of protective factors, in addition to risk factors, may identify potential treatment goals.


In adults, attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD)have certain overlapping symptoms, which can lead to uncertainty regarding theboundaries of the two disorders. Despite evidence of cognitive impairments in bothdisorders separately, such as in attentional and inhibitory processes, data on directcomparisons across ADHD and BD on cognitive–neurophysiological measures are as yetlimited.We directly compared cognitive performance and event-related potential measures from acued continuous performance test in 20 women with ADHD, 20 women with BD (currentlyeuthymic) and 20 control women.p < 0.05). BothADHD and BD groups showed a reduced NoGo-P3, reflecting inhibitory control, comparedwith controls (both p < 0.05). In addition, the contingentnegative variation was significantly reduced in the ADHD group (p =0.05), with a trend in the BD group (p = 0.07), compared withcontrols.The NoGo-N2 was attenuated in women with BD, reflecting reduced conflict monitoring,compared with women with ADHD and controls  andoverlapping neurophysiological impairments in women with ADHD and women with BD. The identifiedneurophysiological parameters further our understanding of neurophysiologicalimpairments in women with ADHD and BD, and are candidate biomarkers that may aid in theidentification of the diagnostic boundaries of the two disorders. Of note, ADHDsymptoms are chronic and trait-like, while BD symptoms of mania and depression tend to occurfor a distinct period of time  and bipolar disorder (BD) are commonpsychiatric conditions in adults, affecting around 2–4% and 1–2% of the adult population,respectively provides a direct measure of covert brain activity underlying behavioural performance withmillisecond temporal resolution, and may enable a sensitive comparison of cognitive profilesin ADHD and BD  in auditory tasks . In brief, ADHD was excludedin the BD group after conducting the Diagnostic Interview for ADHD in Adults .Diagnosis in the clinical groups was confirmed by checking medical records for details ofdiagnosis and psychiatric history, following Diagnostic and Statistical Manual of MentalDisorders, 4th edition (DSM-IV) criteria APA, . All of F2,59 = 1.63, p = 0.21), with a meanage of 37.40 (s.d. = 7.70) for the ADHD group, 40.30 (s.d. = 7.70) forthe BD group and 36.7 (s.d. = 4.30) for the control group. Participants’intelligence quotients (IQs) were assessed with the Wechsler Abbreviated Scale ofIntelligence, fourth edition , with mean IQs of 104 (s.d. = 17.90) for ADHD, 108(s.d. = 12.50) for BD and 112 (s.d. = 14.20) for control participants.Participants with ADHD were asked to stop taking any stimulant medication prescribed fortheir ADHD 48 h prior to the assessment. For ethical reasons, participants were not askedto stop taking mood stabilizers (70% of the BD group), anti-psychotic medication (40% ofthe BD group) or anti-depressants (7% of the ADHD group and 25% of the BD group) they hadbeen prescribed. All participants were asked to refrain from caffeinated drinks andnicotine 2 h prior to the testing session. Ethical approval for the study was granted bythe Camberwell St Giles Research Ethics Committee  and allparticipants provided informed consent.All participants had normal or corrected-to-normal vision. Mean age did not differ bygroup  forcognitive–EEG assessment, IQ assessment and clinical interviews. The task was a CPT-OX,flanker version , RTV (measured as standard deviation of targetreaction time) and number of errors. MRT and RTV were calculated across correctly answeredGo trials. Errors included omission errors , total commissionerrors  and OXO-not-XOX commission errors(response to a Go not following a cue).et al.µV in any channel or witha voltage step greater than 50 µV were automatically rejected. Baselinecorrection was performed using a 500-ms pre-stimulus reference periodThe EEG was recorded from a 62-channel DC-coupled recording system (extended 10–20montage), using a 500 Hz sampling rate, impedances under 10 kΩ, and FCz as the recordingreference. The electro-oculograms were recorded from electrodes above and below the lefteye and at the outer canthi. The EEG data were analysed using Brain Vision Analyser 2.0(Brain Products). Researchers were blind to group status during EEG pre-processing andanalysis. Raw EEG recordings were down-sampled to 256 Hz, re-referenced to the average ofall electrodes, and digitally filtered using Butterworth band-pass filters . All trials were also visually inspected for electrical artefacts  or obvious movement, and sections of datacontaining artefacts were removed manually. Ocular artefacts, corresponding toblink-related and vertical and horizontal eye movements, were identified using the infomaxIndependent Component Analysis algorithm  were averaged based onthree different response conditions: cue, Go and NoGo. Averages only included trials withcorrect responses (Go) or correctly rejected trials (NoGo and cue) and contained at least20 artefact-free segments . ERP measures were identified within the selectedelectrodes and latency windows for which effects were expected to be largest, based onprevious studies . Performance accuracy was generally high aserrors were rare, in line with previous studies on this task , followed by post-hoc t tests. All ERP measures had normal distribution. We reportboth p values (p < 0.05 for significance andp < 0.10 for a trend) and effect sizes (Cohen'sd) for comparisons of cognitive performance and ERP measures. Effectsizes were calculated using the difference in the means, divided by the pooled standarddeviation, where d = 0.20 constitutes a small effect,d = 0.50 a medium effect and d = 0.80 a large effect. Post-hoc analyses revealed a significantdifference between the BD and control groups (p = 0.03) and a trend-leveldifference between the ADHD and control groups (p = 0.06) on RTV, bothwith medium effect sizes (p = 0.93). Groups did notdiffer on MRT .A trend-level effect of group emerged for RTV  and omission errors.Post-hoc analyses indicated that participants with ADHD madesignificantly more commission (p = 0.03) and omission(p = 0.04) errors than controls, with medium and small effect sizes,respectively (p = 0.07) from controls, with a small effect size, but no difference oncommission errors (p = 0.34). The ADHD and BD groups did not differ oncommission (p = 0.20) or omission (p = 0.90) errors. Noeffect of group emerged for OXO-not-XOX commission errors.Trend-level effects emerged on the number of total commission errors.An effect of group did not emerge on the Cue-P3 .Post-hoc comparisons showed a significant difference between the ADHDand control groups (p = 0.05) and a trend-level difference between theBD and control groups (p = 0.09), both with medium effect size (p = 0.85).A trend-level effect of group emerged for the CNV.Post-hoc analyses revealed that the BD group significantly differedfrom the ADHD (p = 0.015) and control (p = 0.04)groups, with large and medium effect sizes, respectively (p = 0.66).There was a significant effect of group on the NoGo-N2.Post-hoc analyses showed that both the ADHD (p = 0.01)and BD (p = 0.03) groups significantly differed from controls,respectively, with large and medium effect sizes (p = 0.88).A significant effect of group emerged on the NoGo-P3.No significant effect of group emerged on the Go-P3 and overlapping  neurophysiological impairments across the disorders. The current studyrepresents the first cognitive–electrophysiological investigation comparing attentional andinhibitory processing in adults with ADHD and adults with BD. In addition, since themajority of previous ERP studies on ADHD have used male samples , both with a mediumeffect size. These results replicate previous studies reporting reduced CNV in individualswith ADHD (McLoughlin et al.et al.et al.et al.et al.et al.The lack of a difference between women with ADHD and controls in the Cue-P3 is inconsistentwith some previous investigations showing a reduced Cue-P3 in ADHD samples (McLoughlinet al.et al.et al.While ERP measures of conflict monitoring differentiated the ADHD and BD groups, cognitiveperformance data did not suggest differences between the two clinical groups. Our cognitiveperformance results potentially suggest poorer performance and higher RTV in both ADHD andBD groups, compared with controls, consistent with previous studies reporting lower accuracyand higher RTV in ADHD and BD independently (Brotman et al.et al.et al.et al.et al.et al.et al.The following limitations of this study should be taken into account when interpretingthese data. First, although the groups were matched on gender, age and IQ, there weredifferences in the prescribed medications that participants with ADHD or BD were taking.While we asked participants with ADHD to stop taking stimulant medications 48 h prior to theassessment, it was not possible, for ethical reasons, to ask participants to stopmood-stabilizing, anti-psychotic or antidepressant medications. Given limited numbers inmedication subgroups, we were not able to directly test the effect of medication on ERPmeasures, which represents a limitation of the current study. The effects of medication aredifficult to control for in cross-disorder comparison studies where different treatments maybe prescribed to different groups of psychiatric patients. Although the understanding of theeffects of medications on ERPs is still limited, previous studies suggest that medicationsmay normalize ERP measures (Anderer et al.et al.In conclusion, our results represent some of the first evidence of disorder-specific andshared impairments in brain processes involved in attentional orienting, conflict monitoringand inhibitory control in women with ADHD and BD, with moderate to large effect sizes. Thisinvestigation of neurophysiological processes furthers our understanding of impairmentsassociated with ADHD and BD, and the identification of objective measures showingdifferences between ADHD and BD may assist in differentiating between the two disorders whentheir distinction is not clear at clinical consultations. If replicated in larger-scalestudies, the neurophysiological biomarkers of distinct patterns in brain activity may aid inthe identification of the diagnostic boundaries of ADHD and BD in adults. More broadly,given that ADHD and BD are both highly heritable disorders, the identifiedneurophysiological indices may represent intermediate phenotypes between diagnosis andgenetic factors influencing a disorder, as suggested by genetic and family studies on ERPindices of attentional and inhibitory processing showing shared familial/genetic influenceswith ADHD (McLoughlin


Belatacept is a novel immunosuppressant that blocks a T-cell costimulation pathway and is approved for use in adult kidney transplant recipients. Its safety and efficacy have not been established after lung transplantation. We present a case of a lung transplant recipient treated with belatacept. A 56-year-old man underwent bilateral lung retransplantation for bronchiolitis obliterans syndrome (BOS). In the third year posttransplant, he developed hemolytic uremic syndrome (HUS) attributed to tacrolimus. Tacrolimus was changed to sirolimus. One month later, he presented with worsening renal function and HUS attributed to sirolimus. Plasmapheresis and steroid pulse were initiated with clinical improvement, and sirolimus was switched to belatacept. He experienced no episodes of cellular rejection but developed recurrent BOS. Complications during treatment included anemia and recurrent pneumonias. The safety and efficacy of belatacept in lung transplantation remains unclear; further studies are needed. While no agents are approved for use in lung transplantation, calcineurin inhibitors (CNIs) such as tacrolimus and cyclosporine are commonly used. They are, however, associated with numerous adverse effects.4 We present a case of a lung transplant recipient who developed hemolytic uremic syndrome (HUS) secondary to tacrolimus and subsequently sirolimus, who was ultimately switched to belatacept.Belatacept is a novel immunosuppressant approved for use in adult kidney transplantation, but has not been studied in lung transplantation. Belatacept is a selective costimulation blocker that binds CD80 and CD86, thereby blocking CD28-mediated costimulation in the T-cell activation cascade.5 Tacrolimus was adjusted to goal trough levels of 8 to 14 µg/L according to protocol. Surveillance bronchoscopy with transbronchial biopsies performed after transplant at months 2, 4, 6, 12, and then annually thereafter were negative for rejection.6 Spirometry was performed monthly for the first 6 months after transplant, at 1 year, and then annually thereafter. His peak forced expiratory volume in 1 second (FEV1) was 3.2 L 2 months posttransplant. Three months after transplant, he developed right bronchus intermedius (BI) stenosis requiring balloon dilation. The right BI stenosis recurred and was ultimately treated with laser ablation.A 56-year-old male underwent bilateral lung retransplantation for bronchiolitis obliterans syndrome (BOS). Immunosuppression included tacrolimus, mycophenolate mofetil (MMF), and prednisone; azithromycin was used for BOS prophylaxis.Two years after lung transplantation, the patient presented with fatigue, anemia, and progressive renal failure. Laboratory data revealed an increase in creatinine from 1.79 to 3.92 mg/dL over 6 months with an estimated glomerular filtration rate of 16 mL/min, spot protein-to-creatinine ratio 1.47, tacrolimus level 8.9 µg/L, hemoglobin 10.3 g/dL, and platelet count 224 000/µL. Urinalysis showed 2+ protein and trace blood. Urine microscopy showed hyaline and waxy casts. Renal biopsy demonstrated thrombotic microangiopathy and severe interstitial fibrosis and tubular atrophy consistent with chronic CNI nephrotoxicity. Tacrolimus was switched to sirolimus.2 These findings were felt to be consistent with HUS attributed to sirolimus, and so sirolimus was discontinued. The patient was treated with plasmapheresis for 4 days and intravenous (IV) methylprednisolone.7 The hemolysis resolved; however, the patient progressed to end-stage renal failure requiring hemodialysis.One month later, he presented with similar complaints. Laboratory data demonstrated a serum creatinine 4.73 mg/dL, hemoglobin 9.0 g/dL, platelet count 111 000/µL, LDH 672 U/L, fibrin D-dimer 1747 ng/mL, and a sirolimus level 14.3 µg/L. One month prior, his sirolimus level was 7.3 µg/L. A peripheral blood smear showed 3 to 4 schistocytes. ADAMTS13 activity was 55% . Acute episodes of thrombocytopenic purpura can be triggered by antibodies against the von Willebrand factor resulting in decreased ADAMTS13 activity.4 MMF was resumed and prednisone maintained at 20 mg per day. He tolerated monthly belatacept dosed at 5 mg/kg without any infusion reactions for 24 months.In collaboration with hematology and renal transplantation colleagues, it was felt the risk of recurrent HUS was too great to rechallenge the patient with either calcineurin or mTOR inhibitors. Belatacept was considered as a novel option for immunosuppression. After verifying the patient’s Epstein–Barr virus (EBV) antibody serostatus, belatacept 10 mg/kg IV was initiated.6 His FEV1 was 2.7 L 3 months prior to belatacept initiation. Six months after belatacept initiation, his FEV1 had fallen to 1.8 L. The decrease in FEV1 was attributed to recurrent stenosis of the right BI that required stenting. After the stent was placed, the patient required frequent readmissions for mucus plugging of the stent complicated by postobstructive pneumonias of bacterial and fungal origin. Further graft surveillance by bronchoscopy or spirometry could not be performed due to patient instability.To assess efficacy of belatacept, transbronchial biopsies and spirometry were obtained. Biopsies were negative for rejection (A0B0) 3 and 6 months after belatacept was initiated.6 It is unclear if his recurrent infections were influenced by belatacept. However, recurrent BI stenosis with stenting increased his risk for recurrent infections prior to belatacept initiation.We present our center’s experience of belatacept use in a lung transplant recipient. Our patient tolerated belatacept infusions and did not have evidence of acute cellular rejection. However, due to recurrent bronchial stenoses and pulmonary infections, we could not definitively assess for chronic allograft rejection (BOS).suggested by our transbronchial biopsies, we have a limited evidence base with which to make this statement. Further studies are needed to confirm this finding. It remains unknown if belatacept is an effective immunosuppressant against chronic or antibody-mediated rejection (AMR). It is also unclear whether belatacept contributed to our patient’s complications including anemia and upper respiratory tract infections or whether they were related to his comorbidities.Although the efficacy of the belatacept to prevent acute cellular rejection is 8 belatacept has been widely used in kidney transplantation.2912 The BENEFIT Study compared a “more intensive” or “less intensive” regimen of belatacept to cyclosporine in kidney transplant recipients. The approved dosing regimen for belatacept is based on the findings from the “less intensive” group. The study showed that belatacept had similar patient and allograft survival at 1 year when compared with cyclosporine.10 Belatacept was associated with superior renal function and a trend toward less chronic allograft nephropathy, despite a higher incidence of early acute rejection.10 Pestana et al found that the rate of acute cellular rejection was comparable in the “low-intensity” belatacept treatment group to cyclosporine patients by 3 years.11 Larsen et al also evaluated donor-specific antibodies (DSA) between treatment groups and found that DSAs were present in 3% of low-intensity belatacept group and 7% of cyclosporine group by month 24. Among kidney transplant recipients with prior acute rejection, the frequency of DSA was higher in those receiving cyclosporine (15%) compared with those receiving low-intensity belatacept (5%).10 Larsen and Pestana also found that DSAs were lower overall in those receiving belatacept; however, the incidence of AMR was not evaluated.11While belatacept has been reported in one other case in lung transplantation in abstract form only,3 Three-year outcomes also showed that overall infection rates were similar between low-intensity belatacept and cyclosporine groups.11 The most common infections included urinary tract infections, nasopharyngitis, and cytomegalovirus (CMV) infections. Serious infection rates were similar between the 2 groups. The incidence of CMV and fungal infections was similar between belatacept and cyclosporine treatment groups.11 Although upper respiratory tract infection rates were similar between belatacept and cyclosporine groups, lung transplant recipients may be at a higher risk of infection as their transplanted allograft is continuously exposed to outside pathogens.10Vincenti et al reported that at 1 year posttransplant the incidence of any infection was similar between low-intensity belatacept and cyclosporine.4 Warnings and precautions with belatacept include increased risk of posttransplant lymphoproliferative disorder (PTLD), malignancy, and serious infection. Notably, clinical trials conducted in the process of seeking belatacept approval by the FDA identified EBV-negative serostatus at the time of transplantation as a strong risk factor for subsequent PTLD.11The Food and Drug Administration (FDA) has issued warnings and precautions based on some of the findings from the BENEFIT and BENEFIT-EXT studies.12 Thus, we suggest belatacept may be cautiously considered as an option in lung transplantation for those intolerant of calcineurin or mTOR inhibitors. Further studies are urgently needed to evaluate its safety and efficacy in other solid organ transplant populations.In general, options for chronic immunosuppression in lung transplantation are limited. Belatacept is a first-in-class immunosuppressant that has been studied in the kidney transplant population as an alternative to CNIs. Although its safety and efficacy has been demonstrated in kidney transplant recipients, it was associated with a higher rate of graft loss and mortality in liver transplant recipients.


The role of diet in the behavior of children has been controversial, but the association of several nutritional factors with childhood behavioral disorders has been continually suggested. We conducted a case-control study to identify dietary patterns associated with attention deficit hyperactivity disorder (ADHD). The study included 192 elementary school students aged seven to 12 years. Three non-consecutive 24-h recall (HR) interviews were employed to assess dietary intake, and 32 predefined food groups were considered in a principal components analysis (PCA). PCA identified four major dietary patterns: the “traditional” pattern, the “seaweed-egg” pattern, the “traditional-healthy” pattern, and the “snack” pattern. The traditional-healthy pattern is characterized by a diet low in fat and high in carbohydrates as well as high intakes of fatty acids and minerals. The multivariate-adjusted odds ratio (OR) of ADHD for the highest tertile of the traditional-healthy pattern in comparison with the lowest tertile was 0.31 (95% CI: 0.12–0.79). The score of the snack pattern was positively associated with the risk of ADHD, but a significant association was observed only in the second tertile. A significant association between ADHD and the dietary pattern score was not found for the other two dietary patterns. In conclusion, the traditional-healthy dietary pattern was associated with lower odds having ADHD. Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed neurobehavioral disorders in childhood, and it often lasts into adulthood . ADHD prThe effect of diet and dietary supplements is unclear, but considerable evidence suggests that dietary factors are associated with childhood behavioral disorders such as ADHD ,13. Low We conducted a hospital-based case-control study using elementary school students who visited several university hospitals in Busan, Korea, from April to September, 2013. ADHD cases were recruited from two university hospitals (Dong-A and Inje University). ADHD was diagnosed by psychiatrists based on the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV). Some children with ADHD have concurrent condition such as tic disorder (motor type), anxiety disorder, oppositional defiant disorder, Tourette’s disorder, depression, and learning disability. A total of 117 cases, which consented to participate in research, were recruited, and age- and sex-matched controls were recruited from three university hospitals . Controls who did not have severe chronic diseases, a history of ADHD diagnosis and any related disease, such as mental disorder and tic disorder were recruited. Additional test using ADHD Rating Scale (ARS) for controls was performed to exclude ADHD cases. After excluding seven participants who did not complete the questionnaire, a total of 202 controls were recruited. To exclude the seasonal variation in dietary intake, the dietary survey season was also matched in the analysis. Frequency matching by grade (two years), sex, and season (three months) was conducted. A total of 192 elementary school students aged seven to 12 years  were finally selected. Each participant and their legal guardian were provided with an informed consent form according to the procedures approved by the Institutional Review Board of the National Cancer Center.The legal guardians of the participants were asked to complete a self-administered questionnaire, which was used to gather information on demographics, lifestyle, and the medical histories of the participants and their parents. A trained interviewer facilitated the 24-h recalls (24HR) interviews face-to-face, and another two non-consecutive 24HR interviews were conducted by telephone between April and September 2013. Individual food intake was calculated using CAN-PRO 4.0 . Mercury and lead exposure from food was calculated using dietary consumption data and their concentrations in 118 core food items. Consumption of omega-3 fatty acids was estimated as the sum of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).t-test for continuous variables and a chi-square test for categorical variables, we compared the general characteristics between students with ADHD and controls. The trend test was performed to analyze the associations between each of the dietary patterns and ADHD using a generalized linear model with adjustments for total energy intake. Odds ratios (ORs) and 95% confidence intervals (CIs) for ADHD were calculated across the tertiles of dietary pattern scores using logistic regression models. The lowest tertile of each dietary pattern was used as the reference. To assess the trend across the tertiles, we assigned median values to each tertile of the dietary pattern scores as a continuous variable. We performed the statistical analysis using SAS version 9.2 . All P values were two-tailed (α = 0.05).Principal-components analysis (PROC FACTOR) was used to extract the participants’ dietary patterns using 32 predefined food groups. We used a varimax rotation to enhance the interpretability of the analyzed factors. We determined how many factors to retain after evaluating the eigenvalue, scree test, and interpretability. The dietary patterns were named according to the factors with the highest scores among the defined food groups for each dietary factor. Each dietary pattern’s factor score was categorized by tertile for further analysis. Using a Student p = 0.008). Father’s educational background and occupation significantly differed between ADHD students and controls .The general characteristics of the study population are presented in PCA identified four major dietary patterns among the 32 food groups, and the associated factor loading scores with absolute values ≥0.20 are shown in P for trend = 0.001; P for trend <0.001, respectively), whereas the percent energy from carbohydrate increased as the score of the traditional-healthy pattern increased (P for trend <0.001). Fatty acids were significantly associated with dietary pattern scores. The traditional pattern score was associated with a high intake of total fatty acids; the seaweed-egg and traditional-healthy pattern scores were associated with high intakes of PUFAs and omega-3 fatty acids, whereas the snack pattern score was negatively associated with the intakes of total fatty acids, PUFAs, and MUFAs. Regarding mineral intake, calcium intake was positively associated with the scores of the traditional, traditional-healthy, and snack patterns, and iron was positively associated with the scores of the traditional and traditional-healthy patterns. Heavy metal exposure via food consumption was also assessed, and mercury was positively associated with the traditional, traditional-healthy, and snack patterns; lead was positively associated with the traditional and snack patterns.The distribution of characteristics by dietary pattern score tertiles is presented in The ORs and 95% CIs of ADHD were analyzed across the tertiles of dietary pattern scores . The OR The present study identified four dietary patterns. The traditional-healthy dietary pattern, characterized by high intakes of kimchi, grains, and bonefish, and low intakes of fast foods and beverages, was associated with lower odds having ADHD. Although the present study focused on dietary factors, significant associations with ADHD were found in father’s education and occupation. Socioeconomic status of children is generally related to household income, and parent’s educational background and occupation. Children from lower socioeconomic status are more likely diagnosed with ADHD than children from higher socioeconomic status in previous studies ,15,16,17The role of diet in the behavior of children has been controversial, but associations between several nutritional factors and child behavior such as ADHD have been continually suggested ,13. FoodThe role of polyunsaturated fatty acids (PUFAs), particularly omega-3 fatty acids, in relation to neurodevelopmental disorders has been studied because omega-3 fatty acids play a critical role in brain development and function . ChildreRegarding mineral intake, calcium was positively associated with the scores of the traditional, traditional-healthy, and snack patterns, and iron was positively associated with the scores of the traditional and traditional-healthy patterns. Zinc was not associated with any of the four pattern scores. Iron deficiency may be associated with ADHD  because Heavy metal exposure via food consumption was also investigated. Mercury was positively associated with the traditional, traditional-healthy, and snack patterns, and lead was positively associated with the traditional and snack patterns. The association between lead exposure and ADHD has been widely studied, and a meta-analysis has reported that lead exposure is positively associated with ADHD symptoms . In a stRecently, associations between dietary patterns and ADHD have been examined in several cross-sectional studies ,20,21. OThe present study has several limitations. As this was a case-control study, it is possible that dietary intake was affected by an individual’s health status and social background. Thus, causal inference cannot be determined. Results could differ by ADHD types, but information about ADHD type was not gathered for subgroup analysis due to small sample size. However, such pattern analyses are useful to further understand the diet of ADHD children as a whole rather than classifying it by a single nutrient or food group.The traditional-healthy dietary pattern, which is characterized by high intakes of kimchi, grains, and bonefish, and low consumption of fast foods and beverages, appears to be negatively associated with ADHD in school-aged Korean children.


Attention-deficit/hyperactivity disorder (ADHD) is a lifelong neurological condition with a profound effect on quality of life. Prescription databases may document pattern of use. In this study we aimed to explore the use in Norway employing such a database.All prescriptions on drugs for the treatment of ADHD between 2004 and 2011, as registered in the Norwegian Prescription Database (NPD) were analyzed. The following drugs were included: Amphetamine, dexamphetamine, methylphenidate and atomoxetine. In-hospital drug administration was excluded. Numbers of users per 1,000 inhabitants were calculated according to gender, age and residence. A sub-analysis compared users born in January-June with those born in July-December. Drug costs were calculated and converted into Euros (€ 1 = N.kr 7.4540).Drugs for the treatment of ADHD was significantly more often prescribed in northern Norway than in any other Norwegian health region (P < 0.001). Within the northern region, Nordland County was the “culprit” (P < 0.02). Compared to Norwegian figures, significantly more females (aged 10-19 years) were treated in northern Norway [male/female ratios 3:1 and 2.2:1 (P < 0.01)] and especially in Nordland County (ratio 2.1:1). The subanalysis did not indicate a northern overtreatment of those being a younger group in their grade. The annual drug cost per user in Norway was € 919.The prescription rate was significantly higher in northern Norway and Nordland County was the culprit. A prescription database may be a tool for monitoring the national use of these drugs. Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric condition characterized by core symptoms of inattentiveness, hyperactivity, and impulsivity . It is pMedical treatment may reduce the negative impact that untreated ADHD has on life functioning, but does not usually normalize the recipients . The mulwww.norpd.no) as the registry includes all drugs prescribed in Norway to Norwegian patients.Patients with ADHD may be treated in the primary and specialized health care. Consequently, a high frequency of care in the specialized health care (SHC) in one region may simply be due to less activity in the primary health care (PHC) and vice versa. To clarify the total medical treatment of ADHD, we employed the Norwegian Prescription Database (NPD). Medical treatment of ADHD can be monitored employing the NPD .An ADHD drug user was defined as a person who had at least one prescription dispensed in a pharmacy each year. The number of users per year was calculated in all four health regions  and in the three counties of Northern Norway . The location of Norway at the top of Europe and its three northern counties are visualised in st and June 30th and group B of users born between July 1st and December 31st.ADHD is an underlying neurological problem and consequently incidence rates should not vary from one birth date to the next. Children born during the second half of the year are a younger group in their grade and the resulting differences in behaviour may lead schoolteachers and health care workers to misinterpret immaturity as symptoms of ADHD. Consequently, a risk of overdiagnosis and overtreatment may occur. To clarify this risk, we sought to indicate the quality of care in terms of the influence of relative age within a grade on the pharmacologic treatment of ADHD. The users were divided into two subgroups and analyzed. Group A consisted of users born between January 1st each year. The number of users was calculated annually and per 1,000 inhabitants of actual age group. Calculations were performed by the NPD and cohorts based on national data on sex, age cohorts  and place of living were employed.In the NPD every individual is allocated a serial number, a so-called pseudonym. This makes it possible to link drug use to individuals and follow their consumption over time, without knowing their identities. Consequently, a person who has collected numerous prescriptions for the same drug is only counted once per year. An inhabitant’s residence was defined as their place of residence on January 1We accessed anonymous and aggregated data from the NPD. Users without a Norwegian personal identification number were excluded. Consequently any non-Norwegian persons given a prescription of an ADHD pharmacotherapy was excluded from the study. The aggregated data were imported into a database at the NNRHA. Microsoft Excel 2007 version was employed for the final database, calculations and statistical analysis. The comparison between regions/counties with regard to users and costs were based on rates. Descriptive statistics and t-test were used for the comparisons. The t-test was used in comparison of incidence rates and a two-sample equal variance (homoscedastic) test was used. Significance was set to 5%. The t-test was carried out two-sided. Most data from the NPD was available on the Web free of cost, but we did also purchase (€ 805) extracted anonymous data of users according to month of birth (first or last six months of the year). As we imported only aggregated data, no ethical committee or Data Inspectorate approval was necessary. Consequently no approval from the Regional Committees for Medical and Health Research Ethics (REK) was necessary. Similarly, no approval from the Norwegian Social Science Data Services (NSD) was required.Drugs for ADHD were significantly more often prescribed to children and youths in northern Norway (P < 0.001). There were 44% and 25% more users in the northern region than in Norway in the age groups 0-9 years  and 10-1Details are shown in To elucidate the higher figures revealed in the northern region, we analyzed figures of the three counties of northern Norway . Nordland County was clearly the “culprit”. The standardized number of users was significantly higher in this county compared with Finnmark County (P < 0.001) and Troms County (P < 0.001). Details are shown in Looking at male/female ratio, boys dominated the age group 0-9 years by 4:1 and there were no differences between regions. In the age group 10-19 years, the male/female ratio was significantly lower in the northern region (P < 0.01) (2.2:1 versus 3:1). Again Nordland County was the “culprit” . Consequently, the more common use of ADHD drugs in northern Norway within the age group 10-19 years was especially observed among females and in Nordland County. Details are shown in st and June 30th with those born between July 1st and December 31st. However, we did not detect any significant differences indicating an overuse or deviation in northern Norway.It could be speculated that the frequent use of drugs for ADHD in Nordland County represented an overuse of these drugs due to malpractice or deviation from national guidelines. We therefore performed a quality of care simulation comparing users born between January 1During study period the mean annual national cost of the ADHD drugs was €13,441,857 and the cost per user per year was € 919. The corresponding figures in the northern region were €1,587,883 and €885. Standardizing these figures according to population  a total of €257,139 would have been saved annually if the national level of consumption had been achieved in northern Norway.In this study, we have documented that drugs for the treatment of ADHD are significantly more often prescribed to children and youths in northern Norway than in any other Norwegian health region. There were significantly more female users (age group of 10-19 years) in the northern region. Nordland County was the “culprit”. In this county, drugs for the treatment of ADHD were significantly more often prescribed than in the other counties of northern Norway. There were no regional differences between subgroups based on month of birth.ADHD affects around 1-3% of children and have been reported affecting between 3-5% of school aged children . In a reInternationally, male/female ratio has been reported 4:1 . This isPossible risk factors for ADHD are genetic factors, alcohol use and smoking habits during pregnancy and psychosocial factors among parents. Smoking during pregnancy has been documented increasing the risk of hyperkinetic disorder in offspring . This DaA high prescription rate in northern Norway and especially in Nordland County does not necessary mean a higher incidence of ADHD. However, the higher incidence of ADHD in northern Norway and especially in Nordland has been documented in a prior study . Surén awww.helsedirektoratet.no), audits and the National Centre of Competence (www.nasjkomp.no) may also be important partners in ensuring an equal quality of care of ADHD-patients throughout the country.Differences between Troms, Finnmark and Nordland County may partly be explained by organizational structure. Norwegian researchers have mentioned that a high number of units  may cause limited experience in the diagnosis and care of ADHD patients in the small units (The monthly willingness to pay (WTP) for an ADHD drug generating full effectiveness, no side-effects and once-daily dosing was estimated € 790 for adolescents and € 360 for adults in a Scandinavian study . We calcDuring study period, the annual total ADHD drug cost was raised (undiscounted) by 65% from €8.3 million (2004) to €13.7 million. This was lower than the figures reported by Based on the NPD we have documented that drugs for the treatment of ADHD are more commonly prescribed in northern Norway. High figure in Nordland County and a significant share of females treated with these drugs in our region were revealed. In the future, the national prescription database should be employed in further quality of care analysis and in the monitoring of the treatment for ADHD in Norway. Furthermore, the high rate of females in northern Norway undergoing medical treatment should be further elucidated.